March

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THE VETERINARY CLINICS OF NORTH AMERICA SMALL ANIMAL PRACTICE

Clinical Theriogenology

AUTUMN P. DAVIDSON, DVM, GUEST EDITOR

V I ,UME 3l .\ NUMBER 2 • MARCH 2001

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CLINICAL THERIOGENOLOGY

GUEST EDITOR AUTUMN P. DAVIDSON, DVM, Diplomate, American College of Veterinary Internal

Medicine; Associate Clinical Professor, Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California; ,and. Director, Veterinary Clinic, Guide Dogs for the Blind, Inc., San Rafael, Califorma

CONTRIBUTORS JANICE 1. CAIN, DVM, Diplomate, American College of Vet~rina? Internal Medicine;

Staff Internist and Consultant in Small Animal ReproductIon, BIshop Ranch Veterinary Center, San Ramon, California

AUTUMN P. DAVIDSON, DVM, Diplomate, American College of Veterinary Internal Medicine; Associate Clinical Professor, Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California; ,and. Director, Veterinary Clinic, Guide Dogs for the Blind, Inc" San Rafael, Califorma

JONI 1. FRESHMAN, DVM, MS, Diplomate, American College of Veterinary Internal Medicine; Director, Canine Consultations, Colorado Springs, Colorado

MELISSA GOODMAN, DVM, Veterinary Referral Center, Frazer, Pennsylvania

DEBORAH S. GRECO, DVM, PhD, Diplomate, American College of Veterinary Internal Medicine; Associate Professor, Department of Clinical Sciences, College of Veterinary Medicine and Biological Sciences, Colorado State University, Fort Collins, Colorado

CLAUDIA A. KIRK, DVM, PhD, Diplomate, American College of Veterinary Nutrition; Diplomate, American College of Veterinary Internal Medicine; Veterinary Clinical Nutritionist, Advanced Research Department, Hill's Science and Technology Center, Topeka, Kansas

BRUNO J. MASSAT, DVM, Diplomate, American College of Veterinary Surgeons; Ithaca, New York

KYL E G. MATHEWS, DVM, MS, Diplomate, American College of Veterinary Surgeons; Assistant Professol~ Department of Clinical Sciences, College of Veterinary Medicine, North " rolin. tat Uni vcrsity, Raleigh, North molina

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PAULA F. MOON, DVM, Diplomate, American College of Veterinary Anesthesiologists; Assistant Professor, Section of Anesthesiology, College of Veterinary Medicine, Cornell University, Ithaca, New York

PETER J. PASCOE, BVSc, Diplomate, American College of Veterinary Anesthesiologists; and Professor of Anesthesiology, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California

MARGARET V. ROOT KUSTRITZ, DVM, PhD, Diplomate, American College of Theriogenologists; and Assistant Clinical Specialist, Department of Small Animal Reproduction, University of Minnesota College of Veterinary Medicine, S1. Paul, Minnesota

MARION S. WILSON, BVMS, MVSc, MRCVS, Director, Glenbred Artificial Breeding Services Ltd., Feilding, New Zealand

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CLINICAL THERIOGENOLOGY

CONTENTS

Preface Autumn P. Davidson

An Overview of Canine Reproductive Services: Getting Started Janice L. Cain

A veterinarian desiring to increase proficiency in canine reproduction needs to become proficient in a variety of reproductive procedures. This article describes commonly performed procedures and gives an overview of how to develop a practice in canine reproduction. Once a veterinarian develops expertise in this area, the base in breeder clients in the practice will rapidly grow.

Ovulation Timing: Concepts and Controversies Melissa Goodman

While the luteinizing hormone (LH) surge has long been accepted as the key event in the estrous cycle of the bitch, historically, there has been no practical way to identify it. In the past, the veterinary practitioner had to rely on general and/or subjective information received from vaginal cytology, physical examination , and observations. With the recent development of in-clinic pro" sterone and LH assays, and the wider availability of laborat ry quantitative progesterone assays, the LH surge can either be id ntified directly or estimated by the detection of changes in I rOt-; '::i t ronco A s a r ' ult, ovulation time can now be predicted wil'l1 hi gh n lira in a I rivot pra ti ctting.

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209

219

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A Logical Approach to Infertility in the Bitch 237 Janice L. Cain

This approach to infertility in the bitch describes what diagnostic methods to perfurm and what thought processes to consider at different phases of the estrous cycle,

Disorders of the Canine Penis 247 Margaret V. Root Kustritz

Function and anatomy of the canine penis are reviewed, Functional abnormalities of the penis described include lack of erection and lack of ejaculation, Physical abnormalities of the penis also are described, including paraphimosis, Diagnosis and treatment options are described,

Clinical Management of the Sub fertile Stud Dog 259 J ani L. Freshman

Breeders invest a great deal of time and money in developing a stud dog; successful breeding is important in making that investment worthwhile. Sub fertility in the stud dog can occur because of lack of libido, inability to breed, or poor semen quality. A detailed history, complete physical examination, and semen evaluation, along with other selected diagnostics can result in successful treatment or management of the sub fertile stud dog.

Surgery of the Canine Vagina and Vulva 271 Kyle G. Mathews

Accurate diagnosis of canine vaginal abnormalities often requires gene~al anesthesia, vaginoscopy, and contrast radiography. Abdommal ultrasonography, thoracic radiography, computed tomography, and histopathology may also be advised for the workup of mass lesions prior to surgery. Many procedures such as episioplasty and resection of pedunculated vaginal masses or ede~atous tissue are easily performed with proper planning and eqUIpment (e.g., electrocautery). Consideration should be given to referring more complicated procedures, such as resection of large vaginal masses or vaginal stenoses, to a board certified surgeon, Finally, preoperative placement of a fentanyl patch and pre- or postoperative epidural anal~esia are highly recommended for any vulvo-vaginal surgical procedure.

Transcervical Insemination Techniques in the Bitch 29'1 Marion S. Wilson

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insemination enables intrauterine deposition of semen, to be achieved without the risks, time, and costs associated with anesthesia and surgery The results achieved with this method of insemination are on a par with the best results recorded following the use of frozen semen, Endoscopic transcervical catheterization has many other applications that make it a valuable technique in canine theriogenology, The overwhelmingly positive reaction from clients makes this a technique well worth learning,

Uterine and Fetal Monitoring in the Bitch Autumn P. Davidson

The use of uterine and fetal monitoring improves the outcome of canine obstetrics, Much of the guesswork of managing whelping can be eliminated, At normal term, absolute indications for cesarean section are detected with monitoring, before multiple fetal deaths or any serious maternal compromise occurs. Bitches with previous history of cesarean section may be able to whelp vaginally successfully, having medical intervention based on monitoring. The anxiety level of owners during whelping is diminished, and the level of participation of the veterinarian improves.

Periparturient and Neonatal Anesthesia Peter J. Pascoe and Paula F. Moon

Small animal patients may need to be anesthetized in the periparturient period for emergency, nonobstetric reasons, elective ovariohysterectomy, or cesarean section. In each case, the physiologic changes in the dam must be accounted for in designing an anesthetic protocol, but the requirements of the fetuses will be different. Subsequent to birth, the neonatal animal may need to be anesthetized, and the unique physiology and pharmacology at this age is described.

Neonatal Critical Care Paula F. Moon, Bruno J. Massat, and Peter J. Pascoe

The quality of the first few minutes of a newborn's life has important and lasting consequences on its entire life. Hence, the care a newborn receives is critical. Recommendations for po tdelivery resuscitation techniques are reviewed. The remainder of the article focuses on the critically ill neonate, possible lInderlying diseases, and methods of supportive therapy.

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305

315

343

369

vii

Nutritional considerations must therefore begin before conception with optimal feeding of the dam. This article reviews key nutritional considerations for reproduction in the queen and bitch and discusses the impact of common nutritional deficiencies and excesses throughout perinatal growth. Factors important in maternal milk for optimal development of the neonate as well as functional foods that show promise toward enhancing the health of growing puppies and kittens are discussed.

Congenital and Inherited Renal Disease of Small Animals Deborah S. Greco

Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in c~ts ~d dogs include renal amylOidosiS, renal dysplaSia, polycyshc kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

Diagnosis and Treatment of Juvenile Endocrine Disorders in Puppies and Kittens Deborah S. Greco

Endocrine and metabolic disorders affecting puppies and kittens from birth until 6 months of age may manifest as clinical problems related to growth, water metabolism (polydipsia or polyuria), or as episodic weakness. Endocrine and metabolic disorders that affect stature, such as pituitary or hypothyroid dwarfism, present to the veterinarian for assessment of delayed or aberrant growth. Conversely, juvenile-onset diabetes mellitus and diabetes insipidus cause excessive thirst, urination, and difficulty in housebreaking.

Frustrating Case Presentations in Canine Theriogenology Autunm P. Davidson

The practice of small animal theriogenology is rewarding, but frustrations exist concerning teclmologic advan as ornp nrcd with other species. Reproductive linician ' Siriv ing lo prn Ii 'l' good quality medicine r ad ily id nlify topi H of (0 111111 0 11 'On t\' m :

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393

401

411

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Canine Molecular Genetic Testing Danika L. Metallinos

Inherited diseases are common among dogs. Recent advances in molecular genetics provide the groundwork for the development of genetic tests for the diagnosis and prevention of inherited diseases. As a result of this progress, genetics should become an integral part of veterinary medicine. DNA tests are safe, easy to perform, and reliable if interpreted correctly. Genetic tests only need to be performed once in a dog's lifetime, because the results of DNA testing never change. Veterinarians should be prepared to understand genetic testing and counseling because they are becoming increasingly important to veterinary medicine.

Index

421

433

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May 2001

VACCINES AND VACCINATIONS

Richard B. Ford, DVM, MS, Guest Editor

July 2001

ENDOSCOPY

Lynda Melendez, DVM, MS, Guest Editor

September 2001

ENDOCRINOLOGY

Ellen Behrend, VMD, MS, and Robert Kemppainen, DVM, PhD, Guest Editors

RECENT ISSUES

January 2001

LAMENESS

Walter C. Renberg, DVM, MS, and James K. Roush, DVM, MS, Guest Editors

November 2000

RESPIRATORY MEDICINE AND SURGERY

Philip Padrid, RN, DVM, Guest Editor

September 2000

INFECTIOUS DISEASE AND THE EYE

Jean Stiles, DVM, MS, Guest Editor

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PREFACE

AUTUMN P. DAVIDSON, DVM Guest Editor

Organizing this volume of The Veterinary Clinics of North America: Small Animal Practice has been a rewarding experience, and I look forward to its publication. Managing the voice mail system for small animal reproduction consult calls at the School of Veterinary Medicine, Davis, California, has given me insight to practitioners' areas of interest and concern. It was easy to identify clinicians within the field of small animal theriogenology with expertise in these areas, having worked in concert with them for many years. To my amazement, they all agreed to take time out of their very busy schedules to contribute to this volume. I wholeheartedly thank each one. We all look forward to referring practitioners to this well recognized text.

The field of small animal theriogenology is uniquely diverse, encompassing board certified theriogenologists, internists, surgeons, anesthesiologists, and nutritionists, as well as doctorates of genetics; all have participated in this volume. Additionally, general practitioners with a special interest in and practice limited to theriogenology contributed their excellent knowledge to the effort. These authors illustrate the exciting diversity present in our practice of small animal reproduction. Collaboration among veterinarians practicing small animal reproduction, both nationally and internationally, is increasing. Attendance at scientific meetings devoted to small animal theriogenology reflects this growing interest. Veterinary students and residents in theriogenology and internal medicine seek additional time on small animal reproduction rotations, anticipating future caseloads. The demand for knowledgeable reproductive clinicians is familiar to anyone in small animal practice.

While contemplating this preface, I reviewed the comments of Drs. Shirley J olmston and Stefano Romagnoli prefacing The Veterinary Clinics of North America: SInaI! Anirl'/a/ Practice 21(3): Canine Reproduction, 1991. They enthusiastically a ll d fo r fu rth'r 8tud i in th ar a of early chemical pregnancy diagnosis, nn il (" I'yol rl,!l-lc rvn linl\ ('<1I' ly nt'utl~ r /sp(ly, hill ·d/ xtended semen breedings,

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ment for further studies in assisted reproductive technology, especially for ovum harvest and preservation, molecular genetic screening, immunocontraception, early detection of congenital defects, and fertile estrus induction. We should continue to educate our clients and the public about the pet overpopulation problem and strive to gain control over irresponsible production and problematic placement of pets. We will debate and study canine cloning, and I admit, although I have concerns about the long-term outcome of developing this technique, if I could clone the perfect Guide Dog, I would!

Small Animal Clinic Veterinary Medical Teachlng Hospital 1 Shields Avenue University of California, Davis Davis, CA 95616

Guide Dogs for the Blind, Inc. San Rafael, CA 94915

AUTUMN P. DAVIDSON, DVM Guest Editor

1'1 J I I I

CLINICAL THERIOGENOLOGY 0195---5616/ 01 $15.00 + .00

AN OVERVIEW OF CANINE REPRODUCTION SERVICES

Getting Started

Janice L. Cain, DVM

Veterinarians offering services in canine reproduction are in demand. Dog breeders are willing to travel considerable distances to obtain quality care for their animals and often look for veterinarians who have expertise in reproductive procedures. The field of canine reproduction has changed over the past decade, and breeders are increasingly aware of new techniques. Developing an expertise in canine reproduction can be challenging and rewarding.

POINTS TO CONSIDER BEFORE STARTING

The veterinarian must become proficient with the knowledge and techniques used in canine reproduction before trying to promote this area of interest. Attending continuing education lectures and keeping abreast of the recent veterinary literature can help to achieve this. Many reproduction procedures such as semen collection, vaginal palpation, and vaginoscopy can be "practiced" on client-owned animals with the owner's consent. Most breeders appreciate the veterinarian's admission that a new procedure is being tried; they can be patient and quite helpful. The same breeders, however, can become extremely upset and critical if the veterinarian is not available when the reproductive services are needed. Many reproductive procedures are performed on weekends

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210 CAIN

and holidays. Breeders seem to prefer availability over expertise, sensing that the latter can be learned over time.

As is the case with any aspect of business, communication between the ve~erinar~an an<Ii clien~ is important for success. This is especially true wIth camne reproduction, because time can be a critical factor. Some suggestions include (1) promptly return telephone calls, (2) educate the reception personnel regarding proper scheduling of appointments and procedures, and (3) have handouts available explaining common proced~res such as ovulation timing (aT) and planning a breeding with chIlled or ~rozen semen. These handouts can include general cost estimates. It IS helpful to send this information to the client before a scheduled appointment.

EQUIPMENT NEEDED

. It is ideal to have a microscope, slides, coverslips, and stains kept m the area where semen collection is performed. Use Diff-Quik stain (Ame~ican S~ientifi.c Produc~s; ~cGr~w Pa.rk, IL) .for vaginal cytology and eIther Dlff-Qmk or Eosm-Nlgrosm stams (SocIety for Theriogenology, Nashville, TN) to examine sperm.

A he:n~cytometer an~ Unopette dilution kits (catalog number 5853, Becton-Dlckmson, Franklm Lakes, NJ) are used for counting sperm as part of ~he complete semen evaluation. A slide warmer is important for evaluatmg sp.erm that has been chilled or frozen, and it should be kept next to the mlCroscope. A warm water bath is helpful for thawing frozen semen and warming chilled semen, and it should also be kept next to the microscope.

A rigid pediatric sigmoidoscope is used for performing vaginos- ' copy, which can be performed easily on nonsedated bitches. Artificial vag~as, collection tubes, and insemination pipettes are used for performmg semen c~llection and a~tificial insemination. All reusable equipment that comes mto contact WIth the sperm should be washed, rinsed, and thoroughly dried before each use.

Ultras?nography is used for performing pregnancy diagnosis and for evaluatmg the female and male reproductive tract for disease. Finally, ~ scope (HOPKINS Telescope with Cysto/Repro Sheath and Bridge with mstrument channel; Karl Storz Veterinary Endoscopy, Goleta, CA) is used for transcervical insemination if the veterinarian is interested in developing expertise with this procedure.

REPRODUCTION SERVICES TO OFFER

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OVERVIEW OF CANINE REPRODUCTION SERVICES 211

and physical examination are conducted as the first step. Reproductive services are recommended only for animals in excellent health.

Prebreeding Examination of the Bitch and Stud Dog

A veterinarian with a special interest in canine reproduction needs to perform thorough prebreeding examinations. Allow time to recommend genetic screening tests appropriate for a given breed such as detection of orthopedic, cardiac, ophthalmologic, coagulation, and thyroid diseases. All breeding dogs are screened for antibodies to Brucella canis, regardless of their breeding history. Many breeders are incorrect in their assumption that only frequently bred dogs require testing or that the disease has been eradicated. This organism can be transmitted by oral contact with contaminated fluids such as urine, semen, or vaginal discharges and does not require natural breeding for transmission.9, 10

Typically, bitches are tested before each breeding, and stud dogs are tested every 3 to 6 months. Antibody testing for B. canis is highly sensitive but not specific; a negative test is reliable, but a positive test can indicate antibodies to another organism. All positive tests are confirmed by more specific testing performed at Cornell University.

Bitch

The veterinarian must develop proficiency with vaginal palpation and vaginoscopy to detect vulvar or vestibular strictures or septa, any of which can interfere with natural breeding and whelping. When the bitch is palpated during anestrus, a normal anatomic narrowing at the junction of the vestibule and vagina (i.e., vaginovestibular junction, which is just cranial to the urethral papilla) can be detected and mistaken for a stricture.6 This perceived narrowing can relax during estrus, and repalpation during estrus is recommended. For bitches with a tight annular ring (i.e., stricture) at the vulvar opening or at the vaginovestibular junction that persists during estrus, natural breeding and whelping may not be possible. The owner is counseled regarding management of the breeding (artificial insemination [AI]) and whelping (cesarean section) that may be required with such bitches. Alternatively, surgery can be considered before breeding. IS

A vaginal septum is a dorsal-to-ventral-oriented embryologic remnant that ori.ginates at the vaginovestibular junction and can extend crani.ally by a variable length.13 Thin pillars or bands of tissue can be brol '11 down t1 igi tn lly in ma ny a s. A longer septum of several centilIle l'I' I', or 1 1'0 1111 k i t' , ~' I LIlt'll l! tend ing to th ' post ervical area, creating n dl Hlhh' VIII',ill" , if! pO' 'ihlt-, ,' l lq', ien l rvHl' ' li on if! I't'cplirnd in Bt l h as s. 1\ .I I l ' I IIII Ji()11 wilit 1111 ' (I Wllt ' l' l'i 'I',ll I'd I " I', Iht ' JlO 11111 ' gvn \'l ir tl ' II1HIlliH ion t ll Vill',ll lil l 11 11111 11 111 I tll ' I"I ' 1 1 II) 1" 111 111 1' 11 11 I II 111',1 /1 Illl jl ' lI 'lllIlI ; tllh llll) ',1t

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212 CAIN

If the bitch is in good general health and free of anatomic defects, the upcoming breeding is discussed and planned. The owner is informed about the advantages of OT and is instructed to return the bitch during proestrus.

Stud Dog

. E.xamin.ation of t~e s~ud dog includes a complete physical examination, u:cludmg exammation of the testes and epididymides and rectal palpatIon of the prostate gland. The scrotum is evaluated for derma tologic diseas~. A sem~n e."aluation is generally performed to complete ~he prebreedl~;g ~xamlI;~~lOn of the stud dog. !f a chilled-semen breeding IS ~lanned, a c~ill-test IS recommended durmg the prebreeding examination. Semen IS collected, evaluated, and extended as for a chilledsemen shipment. The extended semen is then kept by the veterinarian at refrigeration temperature and re-evaluated after 24, 36, and 72 hours. Thi~ allows a determination as to whether chilled-semen breeding is feasI~le for the prop~sed n:ale dog. Additionally, it is a good idea to practic~ semen colle:tlOn WIthout a teaser bitch if it is likely that one is not gomg to be avaIlable at the time of collection for a chilled-semen shipment. This all~ws the veteri~arian to determine that good-quality semen can be obtamed from a gIven stud dog without using a teaser bitch.

Ovulation Timing

Evaluating a bitch during proestrus and estrus to determine when' ~)Vulation is. most likely to occur is referred to as ovulation · timing. This mv~l~e~ senal evaluation of parameters such as serum progesterone and lutemIzmg honnone concentrations, exfoliative vaginal cytology, and appearance of the vaginal mucosa via vaginoscopy.2,3 The goal of OT is to detect the preovulatory .luteinizing hormone surge. The breeding is then :planned to occur. durmg the period of peak fertility, The days of breedmg vary dependmg on whether natural breeding is planned or whether the bitch is to be inseminated with fresh, chilled-extended, or froze~ se.men. Gaining expertise in OT is extremely important for the vet:rmanan who wants to gain success in developing a practice in canme reproduction. (Additional information on OT is presented in another article in this issue.)

Semen Collection and Evaluation

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1. Use a teaser bitch in estrus to increase the stud dog's interest in the procedure,

2. Allow the stud dog to mount the teaser bitch whenever possible. 3. Be sure to fully retract the prepuce behind the bulbus glandis

before complete erection, 4. Use an artificial vagina to collect the semen, 5, Collect the semen into fractions during the ejaculation process to

aid proper evaluation, 6. Allow the dog to complete the copulatory turn during the collec

tion process.

It is advised to perform the semen evaluation immediately rather than submitting it to a reference laboratory. Evaluation of motility is enhanced by use of the slide warmer. A Unopette dilution set and hemocytometer are used to perform the spenn count.6 A slide is prepared to evaluate sperm morphology. Careful inspection of sperm for abnormalities is essential.ll It is possible to have a normal semen evaluation in a dog with a history of poor fertility. Obtaining a second opinion on the semen morphology from a clinical pathologist with a phase contrast microscope is recommended in these cases.

Artificial Insemination

Many dog breeders request an AI for their dogs that do not breed naturally. Before performing the AI procedure, it is important to thoroughly examine the bitch and stud dog for underlying problems. It is also important to determine if the bitch is in her peak fertile period by assessing OT at the time of presentation. When these procedures are followed and semen is collected, evaluated, and inseminated properly, the success rate using this method of breeding can be quite high and similar to that expected with natural breeding.

Most bitches presented for AI are bred using a standard vaginal insemination technique.14 The key to success with this procedure is accurate placement of the insemination pipette. Placement as close to the cervix as possible is desired. Elevating the bitch's hind end immediately after insemination for 5 to 10 minutes aids pooling of semen around the cervix. Stimulation of the bitch's caudal vaginal tract, vestibule, clitoral fossa, or perineal area can cause pelvic thrusting of the bitch and i thought to be an outward sign of uterine contractions that mov th sP ]"111 ranially.

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214 CAIN

avoided. OT is essential to determine the insemination dates, because chilled-extended sperm can have decreased longevity. Another important factor to ensure success with this breeding method concerns the semen handling before chilling. It is extremely important not to have prostatic fluid in the sperm fraction that is chilled.14 This is achieved either by careful fractionation of the ejaculate components during collection or by centrifuging the semen and retaining the semen pellet. Centrifugation in round-bottomed tubes at a relatively low speed for 3 to 5 minutes is recommended. A protective solution is available to add to the ejaculate before centrifugation (Semen Separating Solution; Synbiotics Corporation, San Diego, CA).

Kits that contain all the materials necessary to perform a chilledextended semen shipment, including semen collection materials, separating solution, cryoprotectant extender, and packaging materials, are available for purchase (e.g., Fresh Express, Synbiotics Corporation). The veterinarian performing semen collection must have the kits available, and specific ice packs must be frozen before the date of semen collection. It is advisable to "practice" with the stud dog before the date of semen collection (see section on prebreeding examinations) .

The final point to be emphasized regarding chilled-extended semen collection is the availability of the veterinarian. It is not at all unusual to perform semen collection for this purpose on holidays and weekends. If an overnight carrier service is not available (e.g., Federal Express), counter-to-counter service via an airline often can be arranged.

Insemination with Frozen Semen

Canine semen freezing is a service provided by veterinarians who ' have obtained specialized equipment and have invested considerable time in learning the process. Any licensed veterinarian can perform inseminations with frozen semen, however. Owners can find the veterinarian in their area who has the most experience with the techniques of thawing and handling frozen semen. The most challenging aspect of using frozen semen for breeding is the careful OT that is needed to determine insemination date(s) . Semen has limited longevity after thawing, and the bitch must be inseminated when ova are mature and available for fertilization. Thawing and handling of frozen semen are not difficult provided that the veterinarian has the needed equipment and is willing to follow directions closely.

Insemination with frozen semen can be performed by a variety of methods.s,15 Routine vaginal insemination can be performed if the semen is of excellent quality after thawing. Often, intrauterin in emina ti n (lUI) is performed. This method ensure th ai' !'Il l' s perm b P(l SH the cervix, which can be an adva ntage if S(' l11 t' ll i:-; of Ill dr)', ill,li qlldlil nf lt'r

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sized breeds; any increase in volume only flows out of the cervix, because the potential space within the uterine lumen is limited. Two methods are currently available for lUI. Surgical lUI is relatively easy and is performed via laparotomy. Semen is thawed and drawn into a prewashed and dried 3-mL syringe with a 23-gauge needle. Semen is then transferred from this syringe to a similarly washed 3-mL syringe that has been resterilized. The transfer is performed using sterile technique so as not to contaminate the surgeon. A new 23-gauge needle is then attached to the syringe containing the semen. The uterus is exteriorized, and 1 mL of semen is injected across the uterine wall into the uterine lumen of each horn. It is advisable that veterinarians practice the precise placement of the tip of the needle within the uterine lumen. This can be done on other bitches at the time of ovariohysterectomy using a saline solution.

Another method of lUI is via transcervical insemination (TCI) . The major advantage of TCI is the avoidance of surgery and anesthesia. The procedure of TCI is discussed in another article in this issue.

Evaluation of the Bitch or Stud for Infertility

A logical and practical diagnostic evaluation is well accepted by breeders wanting to try to preserve a genetic line. The most "treatable" cause of apparent infertility is improper breeding management. Typically, the next cycle can be managed using OT procedures and ensuring that the breeding occurs at the correct "time." Compete semen evaluation is recommended for the subfertile male dog. Ruling out underlying disease and prostatic disease is important. Both of these topics are addressed in other articles in this issue.

Pregnancy DiagnOSis, Peri parturient Care, and Cesarean Section

Pregnancy diagnosis can be performed accurately with ultrasonography.19 If a bitch has a history of suspected litter resorption, ultrasonography is the only method to monitor early gestation. Recommendations for using Whelpwise (Veterinary Perinatal Specialties, Wheat Ridge, CO) can be discussed, and availability for performing a cesarean section can be assessed. Details of this topic can be found in another article in thii ' U .

Troatmont of PYOITI trn flnd Metritis

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216 CAIN

treat-not only for the immediate health of the bitch but in terms of her future fertility when she produces a litter. Case selection must be considered carefully, because medical therapy should be reserved for animals that are medically stable and have future reproductive potential. Ovariohysterectomy, after appropriate medical stabilization, remains the treatment of choice for bitches over 7 years of age or if signs of systemic sepsis are present.

Many protocols have been proposed for the effective treatment of open-cervix pyometra and postpartum metritis using prostaglandin F2a (PGF2a).4 These protocols use the natural hormone dinoprost tromethamine, which is marketed as Lutalyse or Prostin (Pharmacia, Kalamazoo, MI). Dosage recommendations range from 0.1 to 0.2 mg/kg of body weight administered subcutaneously every 12 to 24 hours for 5 to 7 days. Some bitches require a longer duration of therapy to eliminate uterine luminal fluid as determined by ultrasonography. Concurrent administration of antimicrobial therapy, either broad-spectrum or based on the culture and sensitivity results from the cranial vagina, is indicated.

Alternatives to the Management of Mismating

Treatment with estrogen products, including diethylstilbestrol, is contraindicated for the management of misbreeding; other reliable and safe protocols are available. I ,16 Prostaglandin therapy early in diestrus can cause transient or permanent luteolysisand prevent continuation of pregnancy. Fetal contents are absorbed and outward signs of abortion are not detected when PGF2a is administered in early diestrus. In one ' controlled study, PGF2a was administered to bitches (0.25 mg/kg subcutaneously twice daily for 4 days) beginning between days 5 and 19 of diestrus.12 Pregnancy was not detected after therapy in 25 purposefully bred bitches. It is important to realize that this protocol uses PGF2a therapy before the detection of pregnancy. Because not all bred bitches become pregnant, some nonpregnant bitches would be unnecessarily treated with this regimen.

Owners may elect to wait until pregnancy can be diagnosed in their mismated bitches. After day 30 of gestation, PGF2a can be administered to induce abortion. Ultrasonography is performed to confirm the pregnancy and is repeated during the treatment period to determine the end point of therapy, because some bitches can partially abort their litters and carry remaining pups to term. The following protocol ha be n reliably successful: 0.1 mg/kg of PGF2a administ red sub utaneoll Iy three times daily for 2 days; then increase I'he dos to 0.2 n g/ kg administered subcutan OLl ly three l'iln '8 linil 1IIIIil tl horiiol1 ii' ('(lill plete.7 Admini stra tion or mi ,'opl'ol'ioi , II 111'1l11.1 1', llIlld lll I': 1'11 IIII HlIlilil , intravag in nll dnil l ( I :\ 11,/', / 11',) ,'!IIIi' IIIII 'IIII " IV III, 1111' II( :11", 1" 11 1111 '11 1 wn, ((lIIIHI 10 dl 'I 'I'I'I I II' 111" 11 1,,, 11111 ' 111 11"li lld 11\ I III I d ,, \ '11 11 ' l till


posed action of the misoprostol in this regimen is to soften and open the cervix, thus encouraging evacuation of uterine contents.

Another method of pregnancy termination in the bitch is to administer products that decrease prolactin production.16 Prolactin is luteotropic in the bitch, and decreased production of prolactin during the second half of pregnancy can induce luteolysis. Prolactin is under negative control by dopamine such that dopamine agonists decrease prolactin production. The dopaminergic products bromocriptine and cabergoline are luteolytic when administered after day 30 of gestation in the bitch. The use of bromocriptine failed to gain acceptance because it can induce protracted emesis at doses effective to induce abortion. The recent availability of cabergoline (Dostinex; Pharmacia) in the United States has rekindled interest in this method of pregnancy termination, because emesis is uncommonly induced. The use of cabergoline (5 J-1g/kg/ d for 5 days) after day 40 of gestation reliably terminated pregnancy in one preliminary studyF Results were less favorable when administration was begun after day 30 of gestation. Additional studies to determine optimum dosing of cabergoline are needed.

SUMMARY

A veterinarian desiring to increase his or her proficiency in canine reproduction needs to become competent in a variety of reproductive procedures. This article describes commonly performed procedures and gives an overview of how to develop a practice in canine reproduction. Once a veterinarian develops expertise in this area, the base of breeder clients in the practice should rapidly increase.

References

1. Bowen RA, Olson PN, Behrendt MD, et al: Efficacy and toxicity estrogens commonly used to terminate canine pregnancy. JAVMA 186:1467, 1985

2. Cain JL: Introduction [Section on Reproductive System]. In Morgan RV (ed): Handbook of Small Animal Practice, ed 3, Philadelphia, WB Saunders, 1997 p 579

3, Concannon PW, Hansel W, McEntee K: Changes in LH, progesterone and sexual beh avior associated with preovulatory luteinization in the bitch, BioI Reprod 17:604, 1977

4, David.s .n AP: M di cal b,'ea tment of pyometra with prostaglandin F2a in the dog and at, III l3onagllJ'i.1 JD (cd) : K irk 's lIrrent Veterinary Therapy XII, Small Animal Practice,

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218 CAIN

son of intravaginal and intrauterine deposition of semen. J Reprod Fertil Suppl 47:325, 1993

9. Johnson CA: Management of Brucella canis outbreaks in breeding kennels . In Bonagura JD (ed): Kirk's Current Veterinary Therapy XII. Small Animal Practice. Philadelphia, WE Saunders, 1995, p 1094 .

10. Johnson CA, Walker RD: Clinical signs and diagnosis of Brucella canis infection. Compend Contin Educ Pract Vet 14:763, 1992

11. Oettle EE: Sperm abnormalities and fertility in the dog. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XII. Small Animal Practice. Philadelphia, WB Saunders, 1995, p 1060

12. Romagnoli SE, Camillo F, Cela M, et al: Clinical use of prostaglandin F20

to induce early abortion in bitches: Serum progesterone, treatment outcome and interval to subsequent oestrus. J Reprod Fertil Suppl 47:425, 1993

13. Root MV, Johnston SD, Johnston GR: Vaginal septa in dogs: 15 cases (1983-1992). JAVMA 206:56,1995

14. Root Kustritz MV, Johnston SD: Artificial insemination in the bitch. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB Saunders, 2000, p 916

15. Silva LOV, Onelin K, Lejeune B, et al: Comparison of intravaginal and intrauterine insemination of bitches with fresh and frozen semen. Vet Rec 138:154, 1996

16. Verstegen, J: Overview of mismating regimens for the bitch. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB Saunders, 2000, p 947

17. Verstegen J, Onc!in K, Silva LDM, et al: Abortion induction in queens and bitches using cabergoline, a specific dopamine agonist. Ann Med Vet 137:251, 1993

18. Wykes PM, Soderberg SF: Congenital abnormalities of the canine vagina and vulva. J Am Anim Hosp Assoc 19:995, 1983

19. Yeager AE, Concannon PW: Ultrasonography of the reproductive tract of the female dog and cat. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XII. Small Animal Practice. Philadelphia, WB Saunders, 1995, p 1040

Address reprint requests to

Janice L. Cain, DVM Bishop Ranch Veterinary Center ~

2000 Bishop Drive San Ramon, CA 94583

CLINICAL THERlOGENOLOGY 0195-5616/01 $15.00 + .00

OVULATION TIMING Concepts and Controversies

Melissa Goodman, DVM

Left to their own behavior and responding to nature's signals, the majority of dogs will breed at a time appropriate to result in conception. Nevertheless, improper timing is the most common reas?n !hat bree~ings fail. 15, 32 This phenomenon is a result of two prope~tles mheren~ In

canine reproduction. The first is that the true fertl~e penod of th~ bItch is short, since mature, fertilizable ova are only VIable for a penod. of 48-72 hours.4,3O In addition, sperm longevity in the female reproductive tract is often extended (6-11 days),9, 10, 18 allowing breedings that occ~r considerably before the fertile period to pro.duce preg:r:ancy. However, If sperm longevity is compromised even slIghtly, or If the number of breedings is limited, matings timed by nature's signals alone ~ay ~~t result in live sperm present during this critic?l ~ime. As a resul~, .IdentlfIcation of the true fertile period will maXlffiIze the probabIlIty of a successful breeding.

INDICATIONS FOR OVULATION TIMING

Apparent Bitch Infertility

The most common cause of failure to conceive in the bitch is poor breeding management (lack of viable seI?en in the ?itch'.s .rep'roductive tract at a tirne that will support conceptIOn). Thus, IdentlfIca.tlOn of the fertile p riod will ensur that breedings occur at the proper hme.

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Abnormal Estrous Cycles

Many bitches ovulate normally, but variations in the estrous cycle sometimes make it difficult or even impossible to identify the correct time to breed by traditional means.

Split heats involve the onset of proestrus with accompanying vulvar swelling and vaginal discharge. Instead of progressing to estrus and standing heat, however, these signs abruptly stop, only to reappear in 2- 10 weeks. These shortened cycles may recur several times, and it is usually the last of these cycles that result in ovulation and fertilityY Ovulation timing procedures will identify the fertile period and the correct time to breed.

Early or late ovulation occurs frequently as a variation from the expecte.d norm. This is a common cause of apparent infertility. Although these bitches are fertile, breedings timed by traditional means will often miss the fertile period.

Silent heats occur when the observable signs of proestrus (e.g., swelling, discharge) are minimal or absent. Ovulation timing procedures will identify these cycles and indicate the correct time for breeding.

Nonovulatory cycles occur when a bitch has a rise in estrogen with all the accompanying signs of proestrus, but never has a luteinizing ~orm.one (LH) surge or rise in progesterone. Hormonal assays will identify those cycles and give the information needed to document the problemY

Breeding with Chilled or Frozen Semen

When performing breedings with chilled or frozen semen, it is imp?rtant to recognize that sperm longevity is compromised by processmgP, 23, 26 Thus, ovulation timing becomes crucially important to the success of these breedings. Inseminations must occur during the actual fertile period for conception to occur.

Breeding with a Subfertile Stud Dog

Often, a stud dog with reduced fertility is still desired for breeding. Accurate ovulation timing will maximize the number of viable sperm ~resent during the true fertile period and increase the chance of concephon.

Breeding with a Subfertile Bitch

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OVULATION TIMING 221

Limited Breeding Access

Occasionally, a stud dog is only available for one or two breedings. Since most bitches will allow mating at times other than the true fertile period,33 the successful accomplishment of one or two matings cannot be relied upon as an indicator that timing was correct. Ovulation timing will ensure that the breeding was accomplished at an optimal time to allow conception.

Disinterested Bitch and/or Stud

Many dogs are presented for artificial insemination because they would not voluntarily breed on their own, frequently because the attempt was either too early or too late. By identifying the fertile period, usually a natural breeding will occur.

Artificial Insemination with Fresh Semen

Artificial insemination is sometimes necessary for either physical or behavioral reasons. Ovulation timing will identify the best time to perform AI to give the best chance of conception.

Shipping Bitches for Breeding

There is some indication that the stress of shipping may cause a release of glucocorticoids. Since glucocorticOid administration has been shown to decrease the level of LH in the serum of dogs,2° it may be prudent to identify the LH surge and ship bitches only after the surge has occurred.

Predicting Whelping Date

Since gestation length is determined by the LH surge/ identification of th LH surge will allow accurate prediction of whelping date.

Owner Information

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222 GOODMAN

REPRODUCTIVE PHYSIOLOGY

The Estrous Cycle

The estrous cycle of the bitch consists of four stages (Fig. 1). Proestrus clinically begins with vulvar swelling and the onset of a bloody vaginal discharge. Endocrinologically, it is characterized by rising estrogen levels. This is the stage of the cycle that prepares the bitch's reproductive tract for the upcoming copulation and conception. Behaviorally, the bitch will attract males but refuse to let them mount. In estrus, bitch behavior will consist of full sexual receptivity. Endocrinologically, estrus begins with the LH surge and is characterized by rising progesterone and declining estrogen levels. This stage is when ovulation and conception occur. Diestrus begins 7-10 days after the LH surge18 and marks the end of standing heat. An abrupt decline in the percentage of cornified cells is seen on vaginal cytology, and progesterone levels remain elevated. In anestrus, progesterone levels drop, either abruptly just prior to parturition or gradually with corpora luteal regression in a nonpregnant bitch. Once considered a quiescent period, it has been shown that both the pituitary gland and the ovaries are active since fluctuations and small surges of follicle stimulating hormone (FSH) and estrogen occur throughout anestrus.S

Major Hormones Involved in the Estrous Cycle

Estrogen

During proestrus, developing ovarian follicles produce increasing amounts of estrogen, resulting in a slow rise in levels from a baseline of

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2-10 pg/ml over a 10- to 14-day period. Estrogen then peaks approximately 2-3 days before estrus, reaching levels of 50-120 pg/ml, followed by a rapid decline that begins about the time of the LH surge. The increase in estrogen causes the observable signs of proestrus, such as bloody vaginal discharge, vulvar swelling, and attraction of male dogs. In addition, increased estrogen causes an increased turnover rate of vaginal epithelial cells, resulting in the progressive cornification seen on vaginal cytology. Also seen is progressive edema of the vaginal mucosa, which can be visualized with endoscopic examination.S

Luteinizing Hormone

At the end of the follicular phase of the estrous cycle, a marked increase in LH over usual baseline values occurs over a 24- to 48-hour period, followed by a return to baseline values?· 27 This surge in LH is thought to take place in response to the decline in the estrogen:proge.ster~ one ratio that occurs as estrogen levels decrease and progesterone nses. The LH surge triggers ovulation and thus makes it the central endocrinologic event in the reproductive cycle of the bitch, wit~ all e~ents following being consistent between bitches? Therefore, dally sen~l measurement of LH to identify the exact date of the LH surge IS the most accurate diagnostic tool for timing breedings.

Progesterone

At the end of the follicular phase, progesterone-secreting corpora lutea are formed in the ovaries. Progesterone levels begin to rise at approximately the time of the LH surge (prior to ?vulation). and continue to increase during the first 15-30 days of gestation, reachmg a peak of 15-90 ng/ml. During the last third of pregnancy, progesterone levels slowly decrease to a plateau of 4-16 ng/ml which is maintained for 1-2 weeks and then drop abruptly to a value below 2 ng/ml 12-24 ~ours prior to whelping. Progesterone is needed to maintain pregnancy m the bitch, both by supporting development of the endometnum and placer:ta and by inhibiting uterine contractions. Rising progesterone acts syner~lstically with declining estrogen to reduce edema of the vulva and vagma, which can be appreciated on vaginoscopic examination. Other observable clinical signs are minimaI.S Serial blood samples perf~rm~d ~very 2-3 days may be used to identify the rise in progesterone whIch mdlcates that the LH surge has occurred; routine breedings may be timed by this para meter.

Ovulation and the Fertile Period

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224 GOODMAN

able ova then remain viable in the oviducts for only 2-3 days.8, 22, 30 Thus, the fertile period begins 4-5 days after the LH surge, when the ovocytes are mature, and terminates 6-8 days after the LH surge, when the ovocytes degrade (Fig. 2). Although a bitch is generally thought of being in season for a period of 3 weeks or longer, the true fertile period, when eggs can actually be fertilized by sperm, is actually quite short (only 3 days in duration).

Gestation Length

Normal parturition may occur anywhere from 56 to 69 days after a fertile mating. This large range exists because of the variability in longevity of sperm in the reproductive tract, allowing conception to occur significantly after the date of the breeding. In the bitch, gestation is 65 days (+ 1 day) from the LH surge.9 This is true regardless of what days the bitch is bred; thus, the most accurate way to predict whelping date is to know the date of the LH surge. This information is invaluable when planning an elective cesarean section, or when deciding if intervention in the whelping process is necessary.

DIAGNOSTIC PROCEDURES

As in any diagnostic procedure, as much information as possible should be gathered; no one test alone will pinpoint breeding times with 100% accuracy. In most cases, a single evaluation, whether it is an examination, a hormonal assay, or cytology, for example, will provide very limited information. Therefore, the bitch should be examined re- -peatedly.

Behavior and Observable Signs

Typically, the bitch will show willingness to accept copulation during estrus.6 Standing heat is caused by the combination of a peak and subsequent decline in estrogen levels acting synergistically with the

Start of

Heat

"

Estrogen Peak

" ~ From 3 to 28 Days

l progeste. rone I Rises and LHPeak

,, :

Ovulation Occurs

"

Fertile Period Begins

_"L

F ertile P eriod Ends

y

~ ~ 2 Dnyo -...-~ 3 OilY. ~ ___ ~ Cllty _

... II"""IIIIU )I"y. ___ +


preovulatory rise in progesterone. This behavior, however, is not directly correlated to the LH surge and so cannot be used to accurately indicate the fertile period.

Observation of vaginal discharge and vulvar turgidity may also be an aid to staging the cycle. Rising estrogen levels during proestrus cause the vulva to be swollen and tense, and vaginal discharge to be heavy and hemorrhagic. As estrogen decreases and progesterone rises with the occurrence of the LH surge, the vulva becomes soft and pliable; at the same time, the vaginal discharge may become scant and straw colored.13,30

While easy to identify in some bitches, in others these changes may be subtle. In addition, many bitches deviate from this typical pattern, showing the typical changes but at a time other than what is expected.

Exfoliative Vaginal Cytology

Examination of the cells on the surface of the vaginal epithelium will give information about the stage of the estrous cycle.2l, 28, 34 Under the influence of rising estrogen levels, the number of layers making up the vaginal epithelium increases dramatically, presumably to provide protection to the mucosa during copulation. Therefore, as estrogen rises during proestrus, the maturation rate of the epithelial cells increases, as does the number of keratinized, cornified epithelial cells seen on a vaginal smear.

Proper technique is important so that the cells obtained are representative of the hormonal changes occurring. The sample should be collected from the anterior vagina because cells from the clitoral fossa and/ or caudal vagina are not as indicative of the stage of the cycle. The slide should be prepared with minimal distortion to the cells, and stained with a modified Wright-Giemsa stain (Diff-Quik, American Scientific Products, McGraw, IL). Emphasis should be placed on determination of the percent cornified versus noncornified cells present; the presence of red blood cells, white blood cells, and bacteria may also be noted.

During early proestrus, when estrogen levels are low, a large number of immature vaginal epithelial cells are present (parabasal and intermediate cell types) . As estrogen levels rise during late proestrus, the cells cornify, becoming superficial epithelial cells. Full cornification is reached when greater than 80% of the cells present on the vaginal smear are cornified superficial epithelial cells. This coincides with peak estrogen levels, but is not related to the fertile period since ovulation is triggered by the LH surge, not an estrogen peak. Full cornification continues throughout estrus, until the "diestral shift" that occurs 7-10 days aft r the U-I su rg ,sign i fying the first day of di -strl.lS.'8 The vaginal 8m '£lr tiwn ch, n)!; 'H ()~ I' ll I II from filii corn iCi ' nli OI1 I'() 40- 60'X, immntur (I il r:lbilHnl nml illll 'I'II H'dill l l ') 1'1·11 \lVI')' II './1 to :16 hplir pl' ri nd . If vn)',i nnl I ' 1()ll l)', iii PI'I ' flll 'II Hld 11111 11 I I II' d I ' 111'.iI I il i l J/l III II II'I ' Ild , ,1 n ' II 'I )! 11II( ,tivl' d l lidY il l1 II I 11 11 ' 1.11 11 111 'f', " , 1l l' l d lllllll , 111111 I I I" 11 ' 111 (, I " ·dl"l W II 1,( ,

ll i li llll ild

226 GOODMAN

Hormonal Assays

Measurement of canine LH, available as an in-clinic assay (Status LH, Synbiotics Corp, San Diego, CA) identifies the preovulatory LH surge and thus, the time of ovulation and the true fertile period. This testing is the most accurate means of ovulation timing, and thus should be considered a "gold standard." Accurate identification of the LH surge is recommended in those instances where there are factors present that could adversely affect conception rates. These include chilled extended semen breedings, frozen semen breedings, breedings with bitches with a history of infertility, breedings with stud dogs with low semen quality, breedings with limited access to the stud dog, or breedings to heavily booked stud dogs. Knowledge of the LH surge will also allow accurate planning of an elective cesarean section. Samples must be drawn daily for LH testing, since the LH surge may have a duration of only 24 hours in many bitches and could be missed if one day was skipped?

Estrogen assays are performed by radioimmunoassay (RIA) by many laboratories. However, the information given is of little value for ovulation timing, since peak estrogen levels are variable from bitch to bitch, and even relative changes do not correlate to ovulation or the fertile period.s, 19

Progesterone assays focus on using changes in progesterone levels to identify the occurrence of the LH surge, ovulation, and the fertile period.6 Progesterone levels may be determined by RIA at many private laboratories; the clinician should verify in advance that the assay has been validated in the low range important for canine ovulation timing, and that the turnaround time for results is practical. When quantitative assays are not available, in-clinic semi-quantitative assays offer a reasonable alternative; several are currently available in the United States.n,17

Basal progesterone levels typically range from 0 to 1 ng/inl during anestrus and proestrus. At the time of the LH surge, serum progesterone rises rapidly (0.8-3.0 ng/mL), continues to rise at ovulation (1.0- 8.0 ng/ mL) and is even higher toward the end of the fertile period (4.0- 20.0 ng/mL).3 By day 21 post-LH surge, progesterone levels range from 15 to 50 ng/mL and should remain elevated for 2- 3 months in all normal bitches, whether pregnant or not.5, 19

By examination of the range and overlap of progesterone values at different points in female reproductive physiology, it becomes clear that no one absolute value of progesterone correlates to any particular stage of the cycle. However, if accurate serial quantitative progesterone assays are obtained, the LH surge may be estimated as the day a di tinct increase in progesterone level is seen . Although this will not be as accurate as actual identification of th ' Lli Sli I')\l' h II , '(' o f nn Lli nHsn , estimation by proges teron r sulC:-l iH slill 11 :-1(' flll 11111 1. nfll' lI II) OI'V widd available to th pra lili ol1('r who II pI '/ oV Id lil \( \l1 11111 II )', (l ll III ) 1H'l'lli 1011 ,11 ba 'i , Wlwn timin )', hnll·d lll )',:J II/li ll i', 11' 111 1 '11111111 1111 VI ' 11 1'11111 ' !' IlII',I ' I'('ron(' ,),14 .1 Il l, Ilid ,11'1)11 )',1 ' II I 11111)',1".11'111 11 1' 11111 01 11 Ill'd , \ It I'll IlI ld' l'l d il'fll 'llil III 11i '1'11I'11\1 ,1" tl l'IlIlI\ 1111'1 111\ 111 1IIi ' 11I1 ,till l !' II 1"Il' I',1'111 ' "ill" '


or the true fertile period. Therefore, these assays should only be used for routine breedings where a wider margin of error is acceptable. A safe rule of thumb to follow is that when testing indicates progesterone has risen above 2 ng/mL, breeding should begin. Regardless of which assay is used, an additional test should always be performed 2---4 days 11fter the first rise is detected to indicate that the cycle has progressed as expected, a functional corpus luteum has been formed, and ovulation has occurred.

When doing progesterone testing for ovulation timing, it is important to remember that at best, detection of changes in progesterone will give an estimation of the LH surge and the fertile period, and thus is not as accurate as actual identification of the LH surge with an Ll-:I assay.

Vaginoscopy

The vaginal mucosa, as a target organ for reproductive hormones, reflects changes in their levels as the estrous cycle progresses. The observation of these changes via vaginoscopy can be a quick, useful tool to t Ise in ovulation timing19, 24 but requires practice by the operator for correct it I terpretation of findings. As with vaginal cytology, the anterior vagina :_hould be examined to provide reliable information. However, it is not 11(, essary to enter the vaginal fornix (anterior to the dorsal fold) to adequately visualize these changes. A rigid endoscope is recommended, but Iwither fiberoptics nor a small diameter scope are required; a 10-inch WelshAllen juvenile proctoscope is ideal. Therefore, this procedure may be perlimned repeatedly without risk of trauma to the cervix or the introduction III potentially pathogenic bacteria into this area of the reproductive tract.

I n p roestrus, the vaginal mucosa becomes markedly edematous as "HI rogen levels increase. The vaginal lumen will be obliterated from Vil'W, and the mucosal surface is smooth and shiny. Vaginal folds are I Ii n k a nd billow out into the lumen as a result of fluid retention, As 1\1 1 I'll approaches, declining estrogen and rising progesterone levels 1', IIIS ' the edema to subside. The vaginal tissue, however, is stretched .Il1d ' 11 nnot r bound quickly enough to accommodate the loss of fluid. As ,I l'I'H ll lt, vaginal folds collap se, and subtle surface wrinkling/crenulation 1lI'l'o l11('s appa l' nl on the vaginal mucosa at the time of the LH surge. 'I'ltl' 11111 ('0:-;8 b om s progreSSively more crenulated, the lumen more dl :J lil)g ui:-l li nb l(', ond tb vaginal folds more flattened as the edema li lllil1i , lw8. Mn il1'1 nl 'ffe ts a rc n d ur ing the fertile period 4-7 days

,tlll'I' IIIl' I,ll , I II');\' . Il die's ITlI s, tlw tnll 0 50 i fl at and variegated . Since Iltl' 1 l'lIil'Vlivl' III v I'S ur \'pi ll w lillr11 IHlv(' di ll1iniHhed, I'h tnu osa is 1IIIiI,I,·, dl)t! 11 (1 11 Ik lll' /1 or Hlqw ri lrj, d 11(' 11111 1'1'1111)',1'. ' 11'( oflvll 14\,(' 1).

~; I' v l'l ',,1 htl d ll' l 11111 II III ' 1(l lI m"' I'" 11 11'(1 11 )',h II \(' 1'/l II '1) 1I1 I'Y I,II' ill 1l1'1I, '\' 1111 1111' 1" '111 '1 1111 11'1 II) )',11111 1'111 11 1"1 '111'1' II I V I) ',I IIII II'II I'V 'I'lli' Itl ll' dlll i 1' 11'111 II I \iI)',l llI d 111111 1),,1' ' 1'1'11\\, ,,1 \ tll\ 111'111' 1'1'111 111)', 1, 11 111111111 1, " '11 11 111 111111 11111111 ' 11 1111 11 11i\ 111 ' 111111 11'1 1111 ' III 111111 111 '1 III Ijl It ' III 1111'1 ' Il ld lll IIIIll r III 11·1 ill I ' " 1111111111 1'1 I 1","1" ,01111" I III )',1 I' ll II " lilllIJlloI lllIl1 \ ,111 ' 11 II I,d Ii' til l lIilllllll 111111 II I' 1IIIIII tl ii I,ll IPI

228 GOODMAN

Other Diagnostic Tools

Ultrasonography may be used to identify ovulation in the bitch. Early attempts were discouraging; the small size of the ovaries and their similarity to close structures make them difficult to visualize. However, recent reports have identified ovulation as occurring when a detectable decrease in the number of follicles is seen during serial imaging. The data have shown a close correlation to the ovulation time established by LH and progesterone levels.31,35 While additional research and refinement are necessary before this method of ovulation timing becomes practical, the results appear promising.

The measurement of glucose in vaginal secretions has been used as a crude guideline for timing breedings by many dog owners. Increased glucose has been identified in vaginal secretions as an inconsistent finding; it is thought to be a result of insulin antagonism that occurs due to altered hormone concentrations at the time of the progesterone rise. This finding is not reliable, however, and so is not recommended for ovulation timing.14

Measurement of electrical conductivity of vaginal mucus is used routinely to time breedings in foxes and has been studied in several other species, including the dog. It was found that electrical resistance increases as estrus approaches and then plateaus at a maximal level for several days, which has been proposed as a result of rising estrogen levels. While it appeared that ovulation occurred at some point during this period of maximum electrical resistance, it has not been shown to be correlated to the LH surge or the fertile period and so cannot be recommended for accurate ovulation timing.16,25

PROTOCOL FOR OVULATION TIMING

Remember that no one test will pinpoint breeding time with absolute accuracy; therefore, always utilize as many diagnostic tools as possible. It is also important to understand the benefits and limitations of each diagnostic tool; individually, the information they reveal is limited. Used in conjunction with each other, according to a diagnostic plan, they can accurately identify the fertile period of the bitch.

Ovulation timing should begin at the first observable signs of proestrus (e.g., vaginal discharge, vulvar swelling) (Table 1). At this time, a breeding history should be obtained and a prebreeding xamin.a hon should be performed. In addition, the pl ans fo r this pnrti ul nr br cding should be discussed to determin m die'll nnd / or Ingis li ';:) 1 fn tors that may influence the accura y of ()vlil nlion linli/I)', IIi 'V(' Hi ll' ii , w (' 1I :1/1 IIw choice of breeding dfl H. Pm (')o, lI1\l1lt ', . 1 1', ,(, '1,\ ' /1 " IIWII I l't·"dlll) ', w ill require th m Ol'l l (1('(' 111'111(' Id( ' 111 11, 111 1( 111 (I I 1111 ' 1"1 '/ 1( , 1"' 1' IHI , WIIt'I 'I 'Ii /

Sl'imnliOI1 of 1111 ' I ,ll 1111')',1' r I11I1 ( 11' ,d I,,, II I ," ,(.d 11 )', 11 1'1'1111'1" ' 1ll ltll ,y

11.11111'11/ rlt ' l l it · 1 ... 1, 1'1'1\ l "'II I " I 'lIlI llI t 111' , ·lv 11"1111 Ii li t II', 1111 " " 1IIIII'rl llll r

hllliloll ,tI d \II I II I I" ld ,.t! .iI Iit ' /l I I I II I ill l l 1\ 111 1 111 1', Il l d • \, 1111 "/ ',\ (1, '1 1 11 11 111

Table 1. OVULATION TIMING PROTOCOL

Pre-breeding examination first 5 days of heat onset Assess general and reproductive health

OVULATION TIMING

Determine degree of accuracy of ovulation timing desired Stage cycle with vaginal cytology + / - vaginoscopy Establish progesterone baseline

Re-examine every 2--4 days until approaching LH surge (> 70% cornification) Stage cycle with vaginal cytology + / - vaginoscopy

Begin hormonal testing

229

Every other day progesterone testing for routine breedings between normal dogs Daily LH testing for breedings requiring higher accuracy, plus progesterone assays

every third day Repeat vaginal cytology + / - vaginoscopy periodically

Identify or estimate LH surge and plan breeding days Check progesterone level 2--4 days after LH surge to document sustained rise Continue vaginal cytology to identify first day of diestrus, if possible

50% cornification) and a baseline progesterone level established (usually 0-1 ng/mL).

Vaginal cytology should be performed every 2---4 days until a significant progression in cornification is seen, usually above 70%. At that point, serial hormonal assays should begin. For routine breedings, progesterone testing may be done every other day, until a rise in progesterone above 2 ng/mL is identified. Breeding should then be done on an every-other-day basis for two or three breedings. When increased accuracy of ovulation timing is necessary (e.g., frozen or chilled semen breedings, infertility cases, breedings with sub fertile stud dogs), daily LH testing is recommended. Once the LH surge is identified, breeding days may be planned. It is useful to perform vaginal cytology each time a blood sample is obtained; cornification should progress to 80- 100%. This maximal cornification usually occurs prior to the fertile period is reached and continues until the onset of diestrus, which is usually a few days after the end of the fertile period. Vaginal cytology may be continued until the diestral shift is identified, which gives a retrospective evaluation of the breeding just completed. In addition, at least one progesteron assay should be performed after the LH surge/initial rise in proge terone i identified to document that levels continue to rise. 'I'hi illustrat ustained corpus luteum function and strongly suggests I'hat an ovule tory ycl has occurred.

V8gin Of-J 01 y may b p rformed throughout the cycle as an adjunct 10 vng lnnl c to logy and hormonal a says, especially when evaluating an 111)11, II nl l' c l(,. II(> i1n vior fi nd oth r ob ''rva tions hould also be made at (,. ll' I, ( . II II II Il .t l 1011, 11111 I('HH W(·i g hl should be put on th's paral11 et 1's.

TIMINe 1m DING.

111 111 11 1', 11 Ill l lll V " 11)1, IV 111 '1 ' 1III ,d 11 1111 '1 "dl y 1111111"1 11 )" III 11 11 1111 1"

'1',111 .1 1\1011 \ ' II III', I'I "I .,It ·1 hll\l ' 111 " "1 111 ,01 111 1"1111 It/ti l il 01"1',( \\ II

230 GOODMAN

be bred together and when. In most situations, the bitch is being transported to the stud dog, sometimes over long distances and at considerable expense. Often, the number of breedings that will be performed is limited, making it even more important that they take place on the correct days. Sometimes, the stud dog has several bitches to breed at the same time; correct information about which bitch to breed on which days will maximize the stud's sperm count and increase the chance of conception for the most females. Other times, a bitch will never show receptivity, or a stud will never voluntarily breed; it is crucial to know when to intervene and perform artificial insemination. In addition, there are bitches that are receptive for an extended period of time; when an unlimited number of breedings is not possible or will decrease the stud's sperm count, the fertile period must be narrowed down to achieve conception (Table 2) .

Semen quality can also determine the necessity for accurate ovulation timing. Since the true fertile period of the bitch is short (the last 2-3 days of the cycle), these are the only days that fertilization can take place. However, most breedings occur before that time; the bitches conceive because a young, healthy stud dog's sperm may live 6-11 days inside a healthy bitch's reproductive tract.lO Therefore, the sperm will still be viable during the fertile period even if the mating took place days previously. With poor quality sperm or low sperm numbers, properly timed breedings can enable an otherwise infertile dog to produce litters. Likewise, a bitch with a compromised reproductive tract might not support sperm for a sustained period of time, so that early breedings will not result in conception, but breedings during the fertile period will be successful.

Normal Stud/Normal Bitch

Efficiency of reproduction is high so little assistance is necessary. This is the only case in which vaginal cytology alone may be used 'as a

Table 2. INDICATIONS FOR OVULATION TIMING

Apparent bitch infertility Abnormal estrous cycles

Split heats Early or late ovulation Silent heats Nonovulatory cycles

Breeding with chilled or frozen semen Breeding with a subfertile s tud dog Breeding with a subfcrtil bi lch Limited br d il1!\ a ('H~ DiRinl' I'C'H I(·t1 I ii<'h tl l1d / 1lI' 11 111 , 1 Al'linl'i ld 1111 1" llI lIlI il l'l ll w illi 11I ' !I I I1I' II II "1 ~: I il l ' I Ii Iif'. I tilt 111'11 1111 1111 ' I '1IIII fl, 1'" ,,1 1, li lli ', \ '111 ' 11 dllf ', rI ,I I1 ' '" ' 111 '1 IliIl"III" I I'OII


general guideline; begin breeding when vaginal smears reach maximal cornification, then breed every 3 days until diestrus is identified. Since the stud is young and healthy, with good semen quality and normal sperm numbers, and the bitch has a healthy reproductive tract that will support sperm for several days, it is not necessary to breed more often than every 3 days. Avoid breeding before full cornification is seen; remember that the bitch's highest fertility is at the end of the cycle, and an excessive number of early breedings will reduce the stud's sperm count for the most fertile days.

Many clients will prefer to better identify the fertile period, whether for reasons of convenience or to increase the chances of conception and maximize litter size. Every other day progesterone testing can be used to estimate the LH surge, with breeding initiated when progesterone rises above baseline (usually greater than 2 ng / mL). Usually two or three breedings at 2- to 3-day intervals are performed.

Normal Stud/Bitch Who Will Not Allow Mating

The most common reason for a normal bitch to refuse to stand for breeding is that attempts are being made either too early or too late in her cycle. Ovulation timing techniques will identify this situation, and a natural breeding will often be accomplished at the appropriate time. There are, however, some bitches who will never show true estrous behavior, whether for an individual stud or in general, and artificial inseminations will need to be performed. Testing protocol and breeding 'chedules should be performed as above.

Disinterested Stud/Normal Bitch

The most common reason for a stud to show little or no interest in breeding a particular bitch is that attempts are being made either too l'ndy or too late. Some studs have poor libido in general and will never br' 'd on thei r own; they can usually be trained to accept semen colleclion and br 'd by artificial insemination. Occasionally, a stud will show d isin te rc l in an individ ual bitch alone, so that artificial insemination is I't'q llir d . 'lb Lin )' .is recommended using every-other-day progesterone I,, 'HA H, il l d il br cd ing schedule should be followed as above.

Bitch with n History of Apparent Infertility

'1'1\1' 11 \111 I 1'\1 11111\ \ 111 1'( '1\11 (\ 11 (0 1' l'Olh '(' pl io n f lilliI'l' i,' illli I"() p t' l' lill1in g (I I 1II'(",d (1) ',1 MII I I Y 11111 '111 111 lil li'lli' I II I I VI ' 11I 11'1\ 111'(,d I II 11 0 1'll ll ii ~ III " d ogM II' " " I II III I)', III" I II , ,t! III , I 111 1 \I " Ii Ii ,." I I Y 1111 ' III ( '( ,Ii , ' 1, w III II I ii I I I (' 1111 I I)',

1'11')', 11 11111 \' ' I 'lil ' I II 11 11)',1' 11111 \' I" ,,, 1111111111'" \ 1111 " \'1'1 \' '1 11 11 ' 1 li l l \, 1"(1) '," I II ·IIlIl, · I,· 1111 1', 111111 1111'10111 II 1'II .d III .dlll \ I '

232 GOODMAN

Bitch with True Infertility

Bitches that have not conceived after breedings to a fertile stud timed based on progesterone testing warrant further infertility investigation. This should include documentation of the LH surge and accurate identification of the fertile period. In some bitches, there may be a significant "mismatch" between the LH surge and expected progesterone changes that can result in inappropriate breeding times based on progesterone assays alone. In addition, certain medical conditions will warrant more accurate ovulation timing than provided with progesterone testing. In bitches with uterine disease, for example, the uterine environment may support sperm for only a short period of time. Therefore, accurate identification of the fertile period with LH testing is recommended, with breedings done during the true fertile period (days 4, 5, and 6 postLH surge).

Stud with Low Sperm Count but Normal Sperm Quality

Although the number of sperm necessary to impregnate a bitch has not been identified, it is generally believed that a minimum number exists, although this number is probably different for different breeds. Since normal sperm live for several days, breeding several days in a row will accumulate enough live sperm to reach this critical number. Early breedings should be avoided since they will only decrease an already compromised sperm count for the most fertile days. Accurate ovulation timing with LH testing is recommended with breedings done on days 4, 5 and 6 post LH surge.

Stud with Normal Sperm Count but Poor Semen Quality

The number of sperm is adequate, but their reduced vigor indicates decreased longevity. Therefore, early breedings prior to the true fertile period are not likely to be successful. Accurate ovulation timing with LH testing with breedings on days 4, 5, and 6 post LH surge should be performed.

Stud with Low Sperm Numbers and Poor Semen Quality

Accurate ovul ation l'iming willi 1.11 l v, (111 )', 11 111)11111 11( ' dUIII ', wi lh breed ings p 'rfornl('d Oil do 1 'I, 'I, dill! () I'ilil l 1.11 1111 1'1',1' , Wil li" lid I 1)(' or 1(\14 1 ill)', Hilol lld ,lid I II Ihl' I I 'I HI IIII IIII 11 11 11 1111 IIIV 1" ' 1111 1'1)1 1111 illd () w

'111.tlil y 11I 1I111I I y, 11\1 ' 11\1 ' 11' 11 11 ' 11\ I lI l lh 1"lti dl ' lll ( .11,1 ,1\, . I t l lll i II I"dl lll'd

, II Ii III I ' I Ii 11'1 I I I \ .I " II ii , I I" " I " " I, 'I I


Breeding with Chilled Extended Semen

Chilled semen is usually somewhat compromised in terms of motility quality and longevity as compared with a fresh semen sample from the same dog.26 In most cases, the sperm will live for 2-3 days after collection, with 1 day used for transport. Therefore, there is little room for error when timing inseminations. As a result, accurate ovulation timing with LH testing is suggested. Two inseminations are usually recommended to cover the fertile period effectively, performed on days 4 and 6 post LH surge.

Breeding with Frozen Semen

Frozen semen, once thawed, lives an even shorter period of time than chilled sperm12, 23, 26 (probably only a few hours) and so must be inseminated only when the ovocytes are mature and ready for fertilizalion. Accurate ovulation timing with LH testing should be done to identify the true fertile period. Inseminations should be performed during days 5 and/or 6 post LH surge, the period of highest fertility.

CONCLUSION

While the LH surge has long been accepted as the key event in the l's trous cycle of the bitch, historically there has been no practical way to identify it. In the past, the veterinary practitioner had to rely on general ,I nd/ or subjective information received from vaginal cytology, physical I ' nminations, and observations. With the recent development of in-clinic progesterone and LH assays, and the wider availability of laboratory qu antitative progesterone assays, the LH surge can either be identified directly or estimated by the detection of changes in progesterone. As a rvs ult, ovulation time can now be predicted with high accuracy in a pr ivate practice setting.

REFERENCES

I. And vl'Sll ll 1< : Arli fi ial in ~ mination and storage of carune semen. In Morrow DA (ed): ( '111'1'(' 111 '1'11 (' 1'11(1 in '1'11 riQI' n logy. Philadelphia, WB Saunders, 1980, pp 661-665

I, ( 'O') l '[IIII1() 1I PW: I)iolllg of gonndntrophin s r 't ion in adu lt and prepubertal female d" )" II, I 1{"p "(11 1 1i" I'l i l '17::1 7, 199:1 ('1 1111 '1 11 111 1>11 I 'W: A I'('v i('w 101' hl'I 'I'd i I1f\ l1l ,ll1l1 gl' nl ~' nl • n I arlifi cinl insC'mination w ith ,h l ll .. dl il I'<I",I'II III' II11 'II , I 'I'III ',' Ii'l'( ',II 1i 'II' M" I" S 111 (111l1 i II 111 1997:1 17, 1997 t 'II I I1 '1 1I1I111I1 I 'W: ('1111 III' 1' " 'I', III1I1" y ,, ",1 1" 11'111 1'11111 11 , V, 'I ( '1111 N, " 'I" A I11 1(, :'1:;. 117B, 11/11(,

I, 1'11 11 111 111 11111 I 'W 1'11 \',11111111 '.1' II I " 'i ,,".1 II I 111111 /1111 1111 1' '1'1 (1' ,1) , 'i lll ll il A I,(' I" II 1\1 '1"I,dllo' 111111 1111,( 11111'111111 \ l 'I ,( llIdl ,II.\II '1 11'" S, 111'11\ 1\1 '1 1'111( " I'I ' 'I '/'I

II I 1'1 1' "11111111 I ' 11 ,111 11 ,1 IV 1\ 1,111\11 ' I I 111 111 1',1'" III I II 1' " 11',1' 111'111 111 ' 1111,( ~' , 1I" li ,, '11 1I 1111 , III I,ll , .I \ 1111 I'" " 111 ,11 11 1 \ 1111, 111 1 ,dlll ll II lilt Idl> i l l ili d I', 1'1111 1 I 1,111 III \ 1'1

234 GOODMAN

7. Concannon PW, Hansel W, Visek WJ: The ovarian cycle of the bi.tch: Plasma estrogen, LH and progesterone. Bioi Reprod 13:112-121, 1975

8. Concannon PW, McCann JP, Temple M: Biology and endocrinology of ovulation, pregnancy and parturition in the dog. J Reprod Fertil 39 (suppl):3-25, 1989

9. Concannon PW, Whaley S, Lein D, et al: Canine gestation leng th: Variation related to time of mating and fertile life of sperm. Am J Vet Res 44:1819- 1921, 1983

10. Doak RL, Hall A, Dale HE: Longevity of spermatazoa in the reproductive tract of the bitch. J Reprod Fertil 13:51-58, 1967

11. Eckersall PD, Harvey MJA: The use of a bovine plasma progesterone ELISA kit to measure progesterone in equine, ovine and canine plasmas. Vet Rec 120:5-8, 1987

12. Farstad W: Bitch fertility after natural mating and after artificial insemination with fresh or frozen semen. J Small Anim Pract 25:561-565, 1984

13. Feldman EC, Nelson RW: Canine female reproduction. In Canine and Feline Endocrinology and Reproduction. Philadelphia, WB Saunders, 1987, pp 421-422.

14. Feldman EC, Nelson RW: Canine female reproduction. In Canine and Feline Endocrinology and Reproduction. Philadelphia, WB Saunders, 1987, p 423

15. Freshman JL: Clinical approach to infertility in the cycling bitch. Vet Clin North Am 21:427-435, 1991

16. Gunzel AR, Koivisto P, Fougner JA: Electrical resistance of vaginal secretion in the bitch. Theriogenology 25:559-570, 1986

17. Hegstad RL, Johnston SD: Use of a rapid, qualitative ELISA technique to determine serum progesterone concentrations in the bitch. Proc Soc Theriogenol 277-287, 1989

18. Holst PA, Phemister RD: Onset of diestrus in the Beagle bitch: Definition and significance. J Vet Res 35:401-406, 1974

19. Jeffcoate IA, Lindsay FEF: Ovulation detection and timing of insemination based on hormone concentrations, vaginal cytology and the endoscopic appearance of the vagina in domestic bitches. J Reprod Fertil 39 (suppl):277- 287, 1989

20. Kemppainen RI, Thompson FN, Lorenz MD, et al: Effects of prednisone on thyrOid and gonadal endocrine function in dogs. J Endocrinol 96:293-302, 1983

21. Linde C, Karlsson I: The correlation between the cytology of the vaginal smear and the time of ovulation in the bitch. J Small Anim Pract 25:77-82, 1984

22. Linde-Forsberg C: Achieving canine pregnancy by using frozen or chilled extended semen. Vet Clin North Am 21:467-485, 1991

23. Linde-Forsberg C, Forsberg M: Fertility in dogs in relation to semen quality and the time and site of insemination with fresh and frozen semen. J Reprod Fertil 39(suppl):299- 310, 1989 .

24. Lindsay FEF: The normal endoscopic appearance of the caudal reproductive tract of the cyclic and non-cyclic bitch: post-uterine endoscopy. J Small Anim Pract 24:1-15, 1983

25. Lofstedt R, Richardson G, Gilbert R, etal: Examination of vaginal mucus in mammals. Therio Handbook 1991.

26. Morton DB, Bruce SG: Semen evaluation, cryoperservation and factors relevant to the use of frozen semen in dogs. J Reprod Fertil 39 (suppl):311-316, 1989

27. Nett TM, Akbar AM, Phemister RD, et al: Levels of luteinizing hormone, etradiol and progesterone in serum during the estrous cycle and pregnancy in the beagle bitch. Proc Soc Exp Bioi Med 148:134-139, 1975

28. Olson PN, Thrall MA, Wykes PM, et al: Vaginal cytology. Part I. A useful tool for staging the canine estrous cycle. Compend Contin Educ Pract Vet 6:288- 297, 1984

29. Phemister RS, Holst PA, Spano JS, et al: Time of ovulation in the b eagle bitch. Bio i Repro 8:74-82, 1973

30. Tsutsui T: Gamete physiology and timing of ov ula tion and fe rtili zation in dogs. J Reprod Fertil 39 (suppl):269- 275, 1989

31. Wallace SS, Mahaffey MB, Miller DM, t a l: Ul tras() nog " I1 J1hi (~ "I IW'"",lI1L'I' of 111(' OV(1l< i( '~ of dogs during the fo lli ula r ~nd ["' I'nl ph"H('H of II ". ,·,11""11" I'y,'I. " 1\ ," 1 VI' I 1{ I 'il

53:209- 215,1 992 32. Van li n, fl 'l'n II, ni"I i" ' '' '" 1:1, ()I. I " II" /I I " ,'I il l '1'1" 11 ,1 /,, 11 1, , 1111111 111', " I d"I'i' I'" IIII' I," /ii i'

of hiliod 1" 'II)',I'liI, " ' "'' ' ' " ,11 "11 1, "111111 V,'I Il", ",I, ' I 1, '(, 1' 1/111 'I:\, Wl ldl 1)1 (, ( '1", 1, "1'" ,1 \' 1'1 1'11 11 1" lV II, , 1 ,1\ p , 111 1111 1, 111 1' II I " ' I,,", Ii I, I( .· 111 ,1,01 ,1, 11


serum luteinizing hormone and time of ovulation in the bitch. Bio Reprod 18:561-570, 1978

34. Wright PI, Parry BW: Cytology of the canine reproductive system. Vet Clin North Am 19:862- 874, 1989

35. Yeager AE, Concannon PW: Association between the preovulatory LH surge and the early ultrasonographic detection of pregnancy and fetal heart beats in beagle dogs. Theriogenology 34:655-665, 1990


Melissa Goodman, DVM Veterinary Referral Center

9 Coffman Street Frazer, PA 19355

e-mail: [email protected]

CLINICAL THERIOGENOLOGY 0195- 5616/01 $15.00 + .00

A LOGICAL APPROACH TO INFERTILITY IN THE BITCH

Janice L. Cain, DVM

Most discussions of infertility in the bitch describe differential diagnoses considering the classification of the estrous cycle as follows: (1) normal estrous cycle, (2) abnormal estrous cycle (abnormal interestrous interval, persistent anestrus, or prolonged estrus), and (3) failure to breed.2,5, 10 The approach to infertility in the bitch presented here differs by describing what diagnostic procedures are performed and what lhought processes are considered at different phases of the estrous cycle, Some breeders contact the veterinarian months in advance of the next estrus, and a prebreeding consultation can be arranged, Other times, the veterinarian is not consulted until the bitch is entering her peak fertile period during estrus, For some bitches, the first indication of infertility is apparent at the time of pregnancy diagnosis, The goal of this article is to help the veterinarian approach the problem of infertility in the hi tch by describing what steps are taken at different stages of the l's trous cycle. After initial presentation, the bitch is evaluated through subsequent phases of her estrous cycle to optimally manage her fertility.

Regardless of which estrous cycle phase the bitch is in at presentat ion, a thorough medical and reproductive history is obtained and a co mplete physical examination is performed. A detailed medical history \' i1 n help to any reveal medical illness that might be an underlying cause of infertility. Important reproductive history information to consider in ' Iu des e trous cycle data such as age at puberty, interestrous interval, ,l ppl'oximate length of proestrus and estrus, and whether the bitch I I ti nil y has signs of p udo yesis. Additionally, for any bitch in which bl'Vl'din g h. s b 'en a tt mpt 'd, inf rma tion hould be obtained on (1)

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238 CAIN

fertility of stud dog(s) used, (2) prior breeding management and ovulation timing (OT), (3) details of individual breedings (i.e., natural or artificial insemination [AI], shipment of the bitch), and (4) diagnostic method used to detect pregnancy (i.e., ultrasonography, palpation, radiography).

A general physical examination is essential before breeding. Bitches with an ongoing significant illness may not be suitable candidates for breeding. The breeding examination also includes digital vaginal palpation and vaginoscopy. Vaginoscopy is performed on nonsedated bitches with a rigid pediatric sigmoidoscope. Vaginoscopy can be performed adequately with an otoscope only in bitches weighing less than 5 kg. Vaginal palpation and vaginoscopy can detect vulvar and vaginovestibular junctional strictures or septa, which can interfere with natural breeding or whelping. IS. 18 Strictures are annular rings of tissue, and septa attached in a dorsal-to-ventral plane can range from thin friable bands of 1 mm in length to a nearly complete wall dividing the vaginal canal. Confirmation of a significant annular strictur,e of the vulva or vaginovestibular junction is made by subsequent examination during the next estrus; hormonal influences of estrus allow many of these narrowed areas to "relax." If a vaginal septum is found, surgical correction is best attempted during anestrus.

PRESENTATION DURING ANESTRUS

It is ideal to have a bitch in anestrus presented for a prebreeding examination. This allows time for a thorough evaluation of previous breeding attempts, and the breeder can be advised of the best breeding plan for the next estrus. There is also time to have the potential stud dog evaluated, and genetic screening tests can be perfonned.

History and Physical Examination

These procedures can be 'performed optimally during anestrus. If the bitch has been unable to breed because of a vaginal anomaly, anestrus is the time during which to consider surgical correction. For the bitch with persistent anestrus, underlying medical illness is considered. Primary anestrus is suspected in a bitch over 2 years of age that has failed to exhibit a pubertal estrus. For this situation, karyotyping to ru l out an intersex condition is advised. 13 Some normal f rt il b it heR an have irregular and infrequent es trou y I 'So Be c lI SC 1'1, I' ~ ii-! no sn Fe and reliable method to indu (,HITIIH in n hil e\) will ) P" I\ L 11'(1 1 11 1)( ' Ii'lL , there is no spe ifi thcr" p In rl'('0I1 111 11'11(1. II In illIPI)1'11I 111 II) d l ' lt- l'lllill l '

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INFERTILITY IN THE BITCH 239

curring. If persistent anestrus is confirmed, possible ovarian disease should be evaluated by abdominal ultrasonography and possibly an exploratory laparotomy.

Genetic Screening and Population Management

Anestrus is the ideal phase of the estrous cycle during which to perform genetic screening tests pertinent to the particular breed. Also, if a "pet quality" bitch is presented for a prebreeding examination, the veterinarian can advise the client of the pet overpopulation disaster in I he United States.

Laboratory Evaluation

A minimal database (complete blood cell count, serum biochemistry profile, and urinalysis) is suggested for any bitch before breeding. Breedi ng is not recommended for any bitch with significant medical problems. /\. screening test for Brucella canis is also obtained.

Abdominal Ultrasonography

Examination of the ovaries and uterus can be performed.19 This I' valuation is strongly recommended in bitches with an abnormal inter('strous interval «4.5 months or >10 months), persistent proestrus or ,'s trus lasting longer than 23 days, a clinical history of abnormal vulvar d ischarges, or fetal resorption. Abnormalities, including ovarian cysts, Ill'op lasia, and uterine disease, can be identified. Normal structures are (J ft n not identifiable during anestrus.

Planning the Breeding

Advice is given regarding stud dog selection and whether natural hI" '(.'d ing or an assisted reproductive procedure is recommended. It is Illl portant to bre d aU bitches with questionable fertility to a known Ivrlilc s tud log that ha had a recent semen evaluation. If any question o ( 11 1nlc fe rti lily xis ts, <'mo th r tu d do i recommended.

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240 CAIN

Shipping the Bitch for Breeding

It is not unusual for owners to "ship" their bitch to be bred via the airlines. This is often stressful for the bitch and can interrupt her proestrus or estrus. If a bitch has been bred and apparently failed to conceive in the past, it is not recommended to ship her for subsequent breedings. The owners should also avoid boarding the bitch at the stud dog's kennel if she is stressed by being away from her home environment, even if she is driven rather than shipped to the location.

Natural Breeding

Natural breeding of the bitch to a known fertile male remains the best chance for fertility. Breedings are planned for days 2, 4, and 6 after the LH peak (which is assigned day 0). If the pair cannot complete t?e breeding event and achieve a successful "inside" tie, fresh semen artIflcial insemination (AI) is recommended.

Fresh Semen Artificial Insemination

If natural breeding does not occur by day 3 after the LH peak, AI is recommended to ensure delivery of semen to the cranial vagina. When performed correctly, fresh semen AI has conception rates comparable to those of natural breeding. Semen is collected from the male dog, evaluated briefly, and immediately inseminated into the bitch.16 This allows examination of semen at the time of breeding, which is helpful if any question of male fertility exists .. If semen l~~ks optimal quality, the addition of a semen extender can Improve motilIty (Fresh Express semen extender; Synbiotics Corporation, San Diego, CA). Ideally, ~o improve the chance of fertility, an alternative male dog that can provIde normal semen is selected.

Chilled-Extended or Frozen Semen Artificial Insemination

If a bitch has a history of questionable fertility and does not seem to conceive, the use of chilled-extended or frozen semen is not recommended. Breeders often choose this breeding method because of stud dog selection even though they realize that ~he chance. of conception is decreased. Conversely, if a bitch has been shipped prevlOus.ly for .bre~ding and has failed to conceive, keeping her .at home and ~nseml11 ~ tmg with chilled-extended semen can be a smtable alternatIve. hlll dextended inseminations are typically performed 0 1 days 4 and t1 afte r the LH peak, and frozen sem 11 is in s min, I'l' d on 1<1 t' 5 (l nt! ) .

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chilled-extended semen on apparently infertile bitches and when using frozen semen. Breeding by lUI is also recommended when using fresh s men for a bitch with no explainable cause of infertility when other breeding methods have failed. Two methods are available for lUI in the bitch: laparotomy and transcervical insemination. (For details on the Hurgical method of lUI, the reader is referred to the overview of canine reproduction in this issue. For a discussion of transcervical insemination, the reader is referred to other articles in this issue.)

PRESENTATION DURING PROESTRUS OR ESTRUS

Initial Evaluation

Often, the bitch is already in proestrus at the time of initial evaluaI ion. This typically removes the veterinarian from the decision-making process of planning the breeding; there is generally not enough time to :dter the breeder's own plan. Hopefully, the appropriate genetic screenII1g tests have been completed before this presentation; if not, it is prudent to advise the owner to wait and breed the bitch at a subseq uent estrus.

At this time, procedures similar to those performed in the bitch pr sented in anestrus include obtaining a complete medical and reproductive history; complete physical examination, including digital vaginal pa lpation and vaginoscopy; minimal database; and B. canis screen. Ex.lInination of the vaginal canal by vaginoscopy at this phase of the ('sl rous cycle is obscured by vaginal edema but can rule out significant olhnormalities, and examination of the vaginal mucosa aids OT.12

Ovulation Timing

l3reeding management error is the most common, and correctable, 1 'il LI se of app~rent infertility in the bitch. The life span of sperm after IlollLlral br dmg can be up to 6 days.4 This is not depended on, however, wh n man aging a bitch for optimal fertility. To ensure the highest 1'011 'p tion rate, the bitch should be bred when mature ova are available lilI' fer ti liza ti on, whi. hi referred to as the fertile period. The fertile period I. dC'l' rmin 'd by T.

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242 CAIN

bitch far pregnancy diagnasis via ultrasanagraphy approximately 21 ta 25 days after breeding.

PRESENTATION DURING DIESTRUS

Initial Evaluation

If the initial examinatian is during the bitch's diestrus phase, it is advised ta evaluate far pregnancy by ultrasanagraphy. Owners wha suspect that their bitch is nat pregnant and realize that they need help .often request ultrasanagraphy. Pregnancy diagnasis and manitaring are alsa advised in the seemingly p regnant bitch ta evaluate far fetal demise and ta ensure that the pregnancy pragresses narmally. A minimal database is .obtained, and breeding management is evaluated retraspectively far the nanpregnant bitch.

Pregnancy Diagnosis

Early pregnancy detectian with ultrasanagraphy is impartant? An indicatian .of litter size and fetal well-being can be determined. Ultrasanagraphy is the .only methad by which ta accurately dacument fetal resarptian. If the bitch is pregnant and has a histary .of fetal resarptian, ultrasanagraphy can be repeated every 1 ta 3 weeks thraughaut gestatian. If the bitch is nat pregnant, ultrasanagraphy is impartant ta help diagnase uterine and .ovarian disease as a cause. Beyand.50 days .of gestatian, radiagraphy is helpful ta caunt fetal skele~ans: ThIS p'raced~re is nat entirely accurate but can give a reasanable estlmatlan .of htter Size. Radiagraphs .obtained after day 55 .of gestatian can be more 'accurate far caunting. Knawing the expected size .of the litter can aid in m.anageI?-ent of whelping and thereby decrease neanatallass. Pregnancy dIagnasis by palpatian alane is nat recammended to manage the bitch far .optimal fertility. It is impassible to detect fetal demise in mast cases when pregnancy diagnasis relies an palpatian.

Fetal Resorption and Spontaneous Abortion

Diagnosing the cause .of fetal resorptian and abartian is the Ina t difficult challenge in evaluating a bitch for infertility. Cause af.f tal resarptian and abartian include uterine diseas ; ath r "m at rnnl fa tors" such as underlying illness, stress, traum a, or toxin eX I OSlIr('; f ' L< I <1110 111 (l

lies; infectious diseas (i . . , B, en /liR, nnill\' IlV"l1L'I-lV i I'll , \<'1 IV\); il llll , IL ,'< ' cOlnmon1.y, lut -,d inRlIffici('l1l' , wlddl 1'1111/11'/ 11) llIllI'lII IIl I' IlI'O)',('/1 ("I'UI)i' S rction .'" I\, I,' S('l'olo)',h ' 1' '1 .11111 \111 11111 1111 11111 11111 111' 1(1 /I 1'l/l/ i:1 11\11 ( 'II V i 1'l'I 'OIIlIIlI 'l ldI 1d , 1111.1 vii II IIIIil l1l11111 1111 ( ' II V 111 1111 II ' '' )', III1t1 I IY II II 111 11 II. ' '11I1 'IIIIII I.d }', II " "I".! \ .tI •• 11 II" , ' 1III dl" , I}',I III I 111 11 III ' ' lil lIl lllll '"


for bacterial culture, althaugh it is difficult to determine pathogens from narmal flara,u Fartunately, bitches that experience lass .of the entire litter during gestatian can have a successful pregnancy with the next attempt even when the cause .of fetal lass is nat determined.

Progesterone Measurement

Serum progesterone cancentration can be assessed during nanpregnant diestrus ta determine if luteal functian is adequate and ta canfirm that avulatian has accurred.3 The detectian .of functianal carp .ora lutea does nat prove that narmal ova were physically .ovulated, hawever. It is possible that if fetal resorptian is detected and a law serum progesterone concentratian is faund (i.e., < 2 ng/mL), the low progesterone secretion did nat cause the fetal loss. It is often difficult to determine which came first, the low progesterone or the fetal compromise. If a low progesterone 'oncentratian is detected at diestrus and fetal viability is confirmed, lreatment with progesterone in ail injected intramuscularly (3 mg/kg) can be attempted to maintain serum pragesterone secretians above 5 ng/mLY Same bitches require daily administratian, although .others I' 'quire treatment every 2 to 3 days. There is concern that inappropriate administration .of progesterone during pregnancy can induce fetal developmental abnormalities; as a result, progesterone supplementatian is not recammended unless it is dacumented ta be necessary.

If the bitch has a low serum progesterone cancentration within S 'veral weeks of breeding, .ovulation failure can be the cause. The bitch hn preovulatory luteinization of follicles, which causes progesterone /'l 'cretian in advance of .ovulation. Measuring progesterone production li S done during OT can detect this. If the progesterone is then measured dgain several weeks later at the time .of pregnancy diagnosis and is at Iwsal levels (i.e., <2 ng/mL), ovulatary failure is suspected. The bitch ('; 111 be experiencing a "split-heat" and may re-enter proestrus or estrus /'loon, when ovulation can .occur. This is not uncammon in young puber-1.11 bitches. Careful monitoring with serum progesterone concentrations hdore and after breeding can be helpful to detect ovulatory failure. '1'1' 'a tment is difficult. The administration of human chorianic gonadatropi n (1000 JU daily intramuscularly [IM] for 2 days) or ganadotropinI'd 'I) ' i n h nnone (50 f.Lg 1M) can be considered.! Success rates using ('i lher p rodu t to treat ovulatary failure have nat been reported. Addilipn; II I innpi ropriat ad illini tration of human chorionic gonadotropin I II' gOll fldoll'tl1 in-rc lc:1 s i ng hormone an a Li e avula tory failure .

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244 CAIN

health of the bitch as well as to offer advice for whelping management. Monitoring of the periparturient bitch is recommended via the Whelpwise system (Veterinary Perinatal Specialties, Wheat Ridge, CO). An elective cesarean section can be planned if advised because of the breed or previous history of the bitch. The expected whelping date is 65 days (± 1 day) after the preovulatory LH surge as determined by OT,3 and an elective cesarean section can be planned for 1 day earlier than the whelping date. Also, if the Whelpwise system is used, the onset of labor can be determined, and a cesarean section can be performed at that time. Either of these methods is far superior to monitoring rectal temperature or counting days from breeding dates.

Future Plans

The first step is to analyze the previous breeding attempt and look for possible errors. Were the appropriate prebreeding evaluations performed? Was underlying disease missed? Was OT performed properly? Did the bitch have a normal estrous cycle? Was the bitch bred naturally to a known fertile stud dog? Was the bitch examined with ultrasonography during early diestrus to diagnose pregnancy? Were appropriate measures taken to ensure that neonatal loss did not occur in the periparturient period? If the answer to any of these questions is no, the entire process can be repeated for another estrous cycle. Also, a different male dog can be used for a subsequent breeding. If either chilled-extended or frozen semen was used, the bitch should be bred naturally to a proven fertile stud dog at the next estrus. Also, IUI with fresh semen should be considered.

When it seems as though everything was done correctly and the bitch apparently failed to conceive or repeatedly loses the litter during gestation, an additional diagnostic evaluation can be considered. During anestrus, uterine biopsies and cultures of the uterine lumen can be obtained via laparotomy or transcervical catheterization. This evaluation can diagnose cystic endometrial hyperplasia or low-grade chronic metritis.9 Persistent degenerative changes to the endometrium are not likely reversible.

As is the case with other species, some bitches remain infertile despite an aggressive logical approach to fertility management. Fortunately, many seemingly infertile bitches can be managed; the v terinarian can either find an underlying cause why the bitch houid not b

,bred or affect a change with a positive outcome.

SUMMARY

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References

1. Cain JL: The use and misuse of reproductive hormones in canine reproduction. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XII. Small Animal Practice. Philadelphia, WB Saunders, 1995, p 1069

2. Cain JL, Davidson AP, Wallace MS, et al: Disorders of canine reproduction. In Morgan RV (ed): Handbook of Small Animal Practice, ed 3. Philadelphia, WB Saunders, 1997, p 627

3. Concannon PW: Clinical and endocrine correlates of canine ovarian cycles and pregnancy. In Kirk RW (ed): Current Veterinary Therapy IX. Small Animal Practice. Philadelphia, WB Saunders, 1986, p 1214

4. Concannon PW, Whaley S, Lein D, et al: Canine gestation length: Variation related to time of mating and fertile life of sperm. Am J Vet Res 44:1819, 1983

5. Feldman EC, Nelson RW: Canine and Feline Endocrinology and Reproduction, ed 2, Philadelphia, WB Saunders, 1996

6, Freshman JL: Current therapeutic recommendations for pregnant dogs. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB Saunders, 2000, p 931

7. Gradil CM, Yeager AE, Concannon PW: Pregnancy diagnosis in the bitch. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB Saunders, 2000, p 918

8. Hashimoto A, Hirai K: Canine herpesvirus infection. In Morrow DA (ed): Current Therapy in Theriogenology, ed 2. Philadelphia, WB Saunders, 1986, p 516

9. Johnson CA: Cystic endometrial hyperplasia, pyometra, and infertility. In Ettinger SW, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders, 1992, p 954

10, Johnston SD: Infertility in the bitch. In Kirk RW, Bonagura JD (eds): Kirk's Current Veterinary Therapy XI. Small Animal Practice. Philadelphia, WB Saunders, 1992, p954

1'1. Linde-Forsberg A, Bolske G: Canine genital mycoplasmas and ureaplasmas, In Bonagura JD (ed): Kirk's Current Veterinary Therapy XII. Small Animal Practice. Philadelphia, WB Saunders, 1995, p 1090

12. Lindsay FEF: Postuterine endoscopy in the bitch. In Tams TR (ed): Small Animal Endoscopy. St Louis, CV Mosby, 1990, P 327

13. Meyers-Wallen VN: CVT update: Inherited disorders of the reproductive tract in dogs and cats. In Bonagura JD (ed): Kirk's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB Saunders, 2000, p 904

14, Purswell BT: Differential diagnosis of canine abortion. In Kirk RW, Bonagura JD (eds): Kirk's Current Veterinary Therapy XI. Small Animal Practice. Philadelphia, WB Smmders, 1992, p 925

. Root MV, Johnston SD, Johnston GR: Vaginal septa in dogs: 15 cases (1983-1992). JAVMA 206:56, 1995

16. Root Kustritz MV, Johnston SD: Artificial insemination in the bitch. In Bonagura JD (ed): KiJ:k's Current Veterinary Therapy XIII. Small Animal Practice. Philadelphia, WB a unders, 2000, p 916

17. S ott-Moncrieff JC, Nelson RW, Bill RL, et al: Serum disposition of exogenous proges,. ronc a ftcr intramuscular adm.inistration in bitches. Am J Vet Res 51:893, 199

I fl. Wyk s PM , od rberg SF: ongenital abnormalities of the canine vagina and vulva. J Am Ani", Il osp Asso J9:995,1983

II) , YCllg<' " AI\, 'on onnon PW: Ultrasonography of the reproductive tract of the female dn!) I1 lld Cil i. III Ih'n(lg rrra )1 (eu): Kirk's l ilT nt V teri nary Th rapy XII, Small Animal I" ',II' I!, '" . 1'IIII II dl'lp lrl.l , WII ,'ll rr"li l' rN, 199'i, p I O~()

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CLINICAL THERIOGENOLOGY 0195-5616/01 $15.00 + .00

DISORDERS OF THE CANINE PENIS

Margaret V. Root Kustritz, DVM, PhD

NORMAL ANATOMY AND PHYSIOLOGY OF THE CANINE PENIS

The canine penis is made up of the root, body, and glans (Fig. 1). The root, or crura penis, is composed of the corpus cavernosum, covered by a thick tunica albuginea, and the ischiocavernosus muscle. It is adhered to the ischial arch between the ischial tuberosities.16 The body, or corpus penis, is made up of two separate erectile bodies separated by a connective tissue septum. The urethra lies ventrally within the body of the penis, enwrapped by the corpus spongiosum; the two sides of the penile body fuse at the base of the os penis.16 The glans of the penis is made up of the bulbus glandis, a globoid or barrel-shaped expansion of the corpus spongiosum, and the pars longa glandis, which contains the os penis overlying the penile urethra. 16, 40 The major vessels supplying l"il.e penis are the internal pudendal and perineal arteries, and venous return is by the internal and external pudendal veins and the dorsal v 'in of the penis. Parasympathetic innervation, via the pelvic nerve, and :-;Yl1l.pathetic innervation, via the hypogastric nerve, are present,

Erection of the penis is mediated by the pelvic nerve and primarily nrfects the glans penis.lo Parasympathetic stimulation causes relaxation of month muscle fibers in the corpus cavernosum, with subsequent \ I . r ased intracavernosal resistance, Arterial flow is increased as a result or ompr sion of the root of the penis and bulbus glandis by the i. 'd io a v rn su and bulbospongiosus muscles, respectively. Erection is ('(lInpl ,t cI by 0 lusion o f v nou outflow by obstruction of the venous

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248 ROOT KUSTRITZ

, " A

Bulbospong;osus m.

" Bul b of penis

" Urethra

.r~ r Retractor penis m.

I Corpus spongiosum penis

I Corpus cavernosum penis

" I Bulbus glandis

I I lPrepuce , f

I I : Pars longa gland;s

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• I Fibrocartilaginous end , of os penis

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Figure 1. Parasagittal section of the canine penis. (From Christensen GC: Angioarchitecture of the canine penis and its role in the process of erection. PhD Thesis, Cornell University, Ithaca, NY, 1953: with permission.) .

lumen at the tunica albuginea and compression by the ischiocavernosus muscle.lO, 42, 63 The pars longa glandis doubles in diameter and elongates. The bulbus glandis doubles in thickness and triples in width when erection is complete.20 Detumescence of the penis is mediated by the hypogastric nerve, which increases arterial resistance, causing a decrease in corpus cavernosal pressure.10 Smooth muscle contraction in sinusoidal walls of the corpus cavernosum permits venous outflow.63

Ejaculation of semen through the penile urethra is mediated by the sympathetic nervous system. Stimulation of the hypogastric nerve causes emission, movement of spermatozoa and seminal fluid into the prostatic urethra, and closure of the neck of the urinary bladder.3, 19, 62 Rhythmic propulSion of semen through the penile urethra is facilitated by contraction of the bulbocavernosus and ischiocavernosus muscles, which are innervated by the somatic pudendal nerve.62

FUNCTIONAL ABNORMALITIES OF THE CANINE PENIS

Erection Failure

Erection failure in dogs m ay be the r u lt of b hnv iora l or rhysi a l causes. Intact male dog that onsis t 'n tl h flw hl'\ '11 dl i'ld l ~ lil1 vd for mounting behavior a r unlil c' l In Wi llil1) ily 11('1'1\ 11'111 Ih h I H 11' 11 11\ I \l1'(1('d ing b ·h avio r on COlIl ll) lIl1d . ~1 1i1l1ld H I I i' 1\\ il l' li ll i',1 II) .IY ihl tlll W 11 11'1', III den n\1l-;! I'I III ' 111 11'11 11 11 I lI " 'I ,ti iI I)', /11 ,1111 ,, \11 1 111111 ' 1' 11 " 1'1111 ' III I I 11 111i, ' dp)', Ill ' 1111111 11 11 i ll ' It ,)" Il lI' v 1'1' 11 '1' \ " 1111,, ' , llI llIll lI llilllI 11111 11111 ,1111 '1 111 " 1" I'Ii "'"

DISORDERS OF THE CANINE PENIS 249

,1 bitch they 'perc~ive to be dominant. Finally, unwillingness to breed Inay b~ seen If a bltc~ has been aggressive toward the male dog, as may () cur If t~e dogs are mtroduced too early in the bitch's season .

~hysl~a.l causes of erection failure in dogs include pain and andror~n msuf~Clen~y. Pain at. the time of mounting and thrusting caused by I~'~nt or. spI~al mflammatl~~ may p revent n?rmal erection in male dogs. I I ostatI~ dIsease ~nd .orchitIs may cause pam at the time of ejaculation; (togs WIth chrome dIsease become unwilling to breed after repeated pCl inful episodes.

Androgen insufficiency is an uncommon cause of erection failure in dogs. The author has never demonstrated decreased serum testosterone concentrations in dogs with abnormal breeding behavior. Normal intact l11ale dogs may have nondetectable concentrations of testosterone in Hc rum; challenge testing is rec?n:mende~ (gonadotropin-releasing hormone [GnRH]; 2 /-Lg/kg admmistered mtramuscularly, with a blood f; <l mple drawn 1 hour later). Normal intact male dogs have a serum ll'st?sterone concentration of greater than 3 ng/mL 1 hour after adminisI rA tIOn of Gn~.~9 Anecd~tal reports exist of castrated male dogs being l\ lpable.of achlevmg erection and a copulatory lock with estrous bitches, H l~ggestmg that el~vated serum androgen concentrations may not be Ilc.cessary for erection. and ~~pulation to occur in all cases. Male dogs lI 1<lY have androgen msuffiClency secondary to testicular atrophy, inI('rsex states, or hypopituitarism.

Di~gnosis of the cause of erection failure requires observation of , ' ()pUI~tIOn ?r seme~ c~llection by manual ejaculation. If the dog seems III be m pam, locahz~tlOn. of the pain response is indicated. If the dog ,toes not seem to be m pam, semen collection in a comfortable environment and in the presence of an estrous bitch is recommended.

Ejaculation Failure

Ejaculation failure in dogs, also called anejaculation or aspermia, l11ay be caus.ed by .lack of sexual maturity, pain, psychologic factors, or !"l liro rade eJaculatIOn. Young male dogs that have not reached sexual lIla lurity may not ejaculate even if capable of normal erection of the jl(' I1I S. l11all -bre d dogs generally reach sexual maturity earlier than I.ll'g '- or giant-br d dogs.

Pilin., .'sP.' ially. that call d by contraction of an infected prostate, 1I 1l ! Inhlb ll' ('1<1 ill ation. III th dog.',o. 65 Joint or spinal pain may prevent 1I 1" ll' dog,' from l11 ountll1g 's lrOliS bit he and howin normal thrusting '"Id ('j'II 'lil ll lio" ,

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250 ROOT KUSTRITZ

may cause incomplete ejaculation include too much activity or too many people in the room, presence of an owner that the dog views as dominant, absence of the owner with a dog that is used to breeding with the owner's assistance, fear of the veterinary environment, and wearing of white laboratory coats. If a negative environmental stimulus is present, the situation in which semen collection is attempted should be changed, and the circumstances in which semen collection is successful should be recorded in the dog's chart for future reference. In dogs with incomplete ejaculation that do not respond to a change in environment, ejaculation may be effected by treatment with GnRH (1- 2 J.Lg / kg administered subcutaneously 2-3 hours once before attempting collection or once weekly for a month before collection or attempted breeding).51 GnRH causes synthesis and release of endogenous luteinizing hormone, with subsequent release of testosterone. This method should not be used routinely in valuable stud dogs; frequent artificially enhanced serum testosterone concentrations may exert negative feedback on the pituitary, which may cause an eventual decline in serum testosterone concentrations and decreased spermatogenesis.

Retrograde ejaculation is flow of semen into the urinary bladder, w ith a significantly decreased semen volume and total number of spermatozoa in the antegrade ejaculate. Retrograde ejaculation has been reported to occur in the dog, but the cause of this condition has not been defined.47, 52 Diagnosis requires collection of a urine sample by cystocentesis after semen collection and comparison of the number of spermatozoa in the antegrade ejaculate and urine sediment. Similarly, urine can be collected by cystocentesis before and after semen collection, with the number of spermatozoa in the urine sediment compared between the two samples. Normal intact male dogs have a few spermatozoa in the urine sediment; dogs with retrograde ejaculation have many spermatozoa in the urine sediment. Treatment with sympathomimetic drugs may effect antegrade ejaculation. Possible therapies include phenylpropanolamine (3 mg/kg twice daily per os) or pseudoephedrine (4-5 mg/kg three times daily or 1 and 3 hours before semen collection or attempted breeding per OS).52

PHYSICAL ABNORMALITIES OF THE CANINE PENIS

Congenital Abnormalities

Penile congenital anomalies described in the dog in lude d ipha lli ,31, 49,67 penile frenulum,s, 6, 26, 32, 55, 57 hypospad ias,l , I ~ p n ile hYI 01 los io,l , :17, 11(, and penile immaturity. 50, SR

Diphallia, or d li p li cCl lio l1 of [I l(' 11' I)i H, hoi 1 111 '1'1) l'I'PI )I·t('li ill 1111'('1' dog in' the vc l'(' rin nl' 1111 '1'1 1111 1'\ ,.11 1'1,1.'/ 1\ 11 1I IId ('01 11'11 1'1'(' 1)1 ,11 11 )01'1 11 111 1111' of l'll(' gl 'IJiI( III l'i II III 'Y li'I II '1 I ill 'll ') di lldll 'llI lll ll II I IIII' 1111 11 111 Y 1,1111 1111'1, "11[11 1I 'dlllll) 1)1 lit l' 111 '111 111 11 ', III 11'11111 11 1' 11t 'ld ll ' II ) " 11 '111'1111 111', 11'."1 II I dll' lllI ll J, I \\'1'11' 1, ,11'111 1011 ' III 111l ' 111111111\ 11 111 1 Il1ld 111 111I11 ,tI III ·ill.l111 1 ,I,


pollakiuria, and inappropriate urination. Diagnosis is by visual inspection .

A penile frenulum is a band of connective tissue joining the ventral portion of the pars longa glandis to either the corpus of the penis or the prepuce.5, 6, 25, 32 It is formed by incomplete dissolution of the androgendependent balanopreputial fold. 25 Dogs with a penile frenulum may be asymptomatic or may present with excessive licking of the penis and prepuce, dermatitis between the rear limbs, phallocampsis (curvature of the penis when erect), and pain when breeding with inability to achieve a copulatory 10ck.6, 26, 32, 55, 57 Diagnosis is by visual inspection. Treatment in symptomatic dogs or those intended for breeding is transection of the frenulum.

Hypospadias is abnormal termination of the penile urethra along the ventral surface of the penis proximal to the normal urethral opening.1, 25 It is classified as glandular, penile, scrotal, or perineal, with increased severity associated with proximal location of the urethral opening. Concurrent genitourinary defects reported include cryptorchid ism, penile hypoplasia, ventral deviation of the penis, and abnormal development of the ventral prepuce.1, 22 Dogs with hypospadias may be dsymptomatic or may present with urinary incontinence and associated inguinal dermatitis.25 Diagnosis is by visual inspection. Treatment varies with location of the urethral opening; glandular hypospadias may require surgical repair of the defect only, penile hypospadias may require partial amputation of the penis and urethra to the level of the urethral orifice, and scrotal and perineal hypospadias necessitate scrotal or periIlea 1 urethrostomy, which may be accompanied by penile amputation. 1, 25

Penile hypoplasia, or abnormal shortening of the glans penis, often is seen in intersex dogs and may be seen concurrent with cryptorchid ism" l, 37, 46 Penile immaturity, also called infantile penis or micropenis, iH the presence of an abnormally small penis relative to the size of the I log.50 A decrease in penile size may be acquired; in a study comparing !,l'n il size in 13- to 15-month-old mixed-breed dogs that had been g()nadectomized at 7 w eeks or 7 months of age or left intact, it was 1'('1 ort d that those dogs gonadectomized at 7 weeks of age had immaIII r' g nitalia characterized by significantly smaller penile diameter, ti('erc s'd ize and radiodensity of the os penis, and immaturity of the III'('PUC ompa red with male dogs gonadectomized at 7 months of age (II' Idt Intel t.0ll The linical significance of acquired penile immaturity 1\1 11'1 II () I bet' n r ' por t d .

'I' ll!' o('cM,ioll ol 111 , I dog has an apparently normal penis that does 1101 1H'(,()I11L' VII );{ )I 'M\' r! Huffi i ' n tly to a ll ow form ation of the copulatory IIH 'I , () I' Iii' , it) wh ich 11ll' engo l');('d bltl bus g lZl nd is is augh t within the I [III II" tl ](' vlil v,1 IIi' II IV ,'HII'OII fl' ll ll ll l " i)1Iri ng th ' 'op ulato r 10 k, 11111 '1,1111 i'\ [l lil l Ili l (I I WI I 1'1 II I 1II'Ili ll.l lll' lii tid hy IIH ' 11 )<) 11 ' dpg I1 llli 11)1 111 '.11 '111111 Iii 11 Jt' VIII', hll t! IIII HIo 'ltl l!l III 'I' 1')1 tl 1l' hill'l l I' I'I) II) () I!' ,'I'l lltill l 11111 \1 /'1111'111 III 11j'I '1I1 1 11 11 '/ 111 IV III II III I' 1111 11'/ " 'I"IIi II Ii 'll vl' 11 ,11 I 1'1"", IloI li' \' 1111 1'1'111 11 11 '\,1'" \\'1 11 11111 1 Ilill lltlll ll lllilllll ' 1111'I il lll1lll' 1111 11 1, 11 '1 101 11,11111111.111 1111111' 11'1'111111 11 11 11 11 1 1l1l1l htld \' II IIII' 11' 1/"1 Id II 11.1111111 1

252 ROOT KUSTRITZ

variation in relative penile and vulvar size in these animals. Artificial insemination can be used to ensure deposition of semen within the bitch's reproductive tract.

Phimosis and Paraphimosis

Phimosis is inability of the male dog to extrude the penis from the prepuce. It may be congenital or acquired, with inflammation, edema, neoplasia, or cicatricial constriction after wound healing causing a stricture at the preputial orifice.4• 27. 30, 50 Diagnosis is by visual inspection. Treatment is surgical enlargement of the preputial orifice.

Paraphimosis is inability of the intact or castrated male dog to retract the nonerect extruded penis into the preputial sheath. Causes include sexual arousal without erection, neurologic disease (encephalitis, intervertebral disk disease), fracture of the os penis, balanoposthitis, constriction at the preputial orifice by a hair ring or scar tissue, abnormal penile swelling (trauma, neoplasia, malicious strangulation), and entrapment of the penis outside the prepuce during penile detumescence. 15, 30, 35 The exposed penile tissue undergoes ischemia, drying, and excoriation, and it is increasingly compromised with prolongation of paraphimosis. Diagnosis is by visual inspection. Conservative forms of therapy, which are most appropriate when the tissue is not severely compromised, include lubrication and replacement of the penis within the prepuce by digital pressure and isolation of the male dog from estrous female dogs or other causes of sexual excitement. Paraphimosis may occur as a learned behavior secondary to penile licking; owners should be cautious not to correct the dog excessively so as not to promote parap'himosis by positive reinforcement (P. Mertens, DVM, MS, personal communication, 2000). Treatment of castrated male dogs with progestogens may alleviate recurrence of the problem. Progestogen therapies recommended include megestrol acetate (Ovaban; Schering: 0.5 mg/ kg once daily per os for a maximum of 30 days or 2.0 mg/ kg once daily per os for 8 days), medroxyprogesterone acetate (2.5 mg/kg subcutaneously every 5 months for a maximum total length of treatment of 1 year), and proligestone (10 mg/kg subcutaneously with a 3-month interval between the first and second doses, a 4-month interval between the second and third doses, and then every 5 months for a maximum total length of trea tment of 1 year) (S. Romagnoli, DVM, MS, personal communication, 2000). General side effects reported with long-term proge togen therapy include temperament changes, increased thir t or t ppclit , 111 , 111111 (1 1' enlargement or lactation, Ii tle n Sfl, Fi n I fl rn llwgn l . Slirgic;)1 Ilwn1 pil 's that may be requir d in Iml l' wid Vllill l', o r Il l<' pi"l'Ilill i,iI (lrin! ,,' r(l r d()g:1 with a gros Iy norl1l ;lI IWlli :1 111 ,11 , '1 11111 ,,1 lli' 1"'ld lll 'Jld III IIII' I Irl'\ 1I 1('1' Ily d igita l I n'S,' III '(' dlHI IlI' ldl(' 11111 1111 11 1 (III II11 dill',' willi ' I'V.·II ' 11 1111111 11 11\ ' ,1I ' jpl'ili'llril ' .1 11111 11)'," 1,1 1111' 1'1 '111 , 1111'1


Persistent Erection (Priapism)

. Persistent penile erection, or priapism, is prolonged penile erection WIthout sexual arousal, causing discomfort and difficult urination.66 Priapism may occur secondary to prolonged or excessive parasympathetic stimulation or as the result of decreased venous outflow from an occlusive thromboembolism or mass lesion.66 Stagnation of blood with subsequent low oxygen and high carbon dioxide concentrations within the corpus cavernosum penis causes edema with further venous occlusion and eventual irreversible fibrosis in the main venous outflow tracts of the penis.66 Ischemic necrosis of the penis results. Reported causes in the d~g m~lude trauma :vhile .mating, chronic distemper encephalomyelitis WIth dIstemper-assocIated mflammatory lesions in the spinal cord, penile thromboembolism, administration of amphetamines, and apparent decreased venous outflow after castration (J. Winsor, DVM, A. Valenti, DVM, personal communication, 1999).17, 18 There is one report of idiopathic priapis~ in the dog.53 Di~gnosis is by visual inspection. Diagnosis of the underlymg cause of the dIsorder may require extensive evaluation of the animal, including assessment of general health with a complete blood cell count, serum chemistry profile, and coagulation profile; complete evaluation of the genitourinary tract with urinalysis, aerobic urine ulture, and radiography or ultrasound; and assessment for mass lesions

in the caudal abdomen. The workup must also be. timely, because treatment options become limited as the penis undergoes progressive ischefmc change. In the dog, the underlying cause of persistent penile erection may not be identified, and the penis usually is irreparably damaged by lhe time of presentation. Castration usually is not effective as a sole Ireatment. Reported treatments include re-establishment of venous outflow by removal of sutures left in the vaginal tunica at castration (J. Winsor, pVM, A. Valenti, DVM, personal communication, 1999), incising I he pems over the bulbus giandis and pars longa glandis through the 1,lInica albuginea and applying pressure to expel free blood and thrombi I rom the corpus cavernosum penis,44 and penile amputation and perineal 1I r throstomy.s3

Balanoposthitis

l3a lanop sthiti is inflammation of the glans penis (balanitis) with l'Il ll o l11itnnt inflamm ation of the preputial mucosa (posthitis). The re-1\()I'lc'(\ ~ ; lLJ S' of bFl IAnoposthiti s in th dog j opportunistic infection with 111 1,'II' ri li l or vil'nl ngl'nts I'hnl 1I1 n or may not b normal preputial flora. 2,

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254 ROOT KUSTRITZ

Klebsiella Sp.28 All these bacteria are normal preputial flora. Mycoplasmas and ureaplasmas have been cultured from the prepuce of dogs with balanoposthitis.14, 34, 54 Mycoplasmas and ureaplasmas also are normal flora of the preputial mucosa of dogs,54 confounding the ability to definitively diagnose these organisms as causative of balanoposthitis in a given animal. In two surveys, Mycoplasma species were cultured from the prepuce in a significantly larger percentage of dogs with balanoposthitis (92%- 95%) than from reproductively normal dogs (64%-70%).14, 54 Mycoplasma canis is the most common isolate.14,34 The significance of ureaplasmas as a cause of balanoposthitis is less well defined; in the one study reported, Ureaplasma species were cultured from 69% of dogs with balanoposthitis and 70% of reproductively normal dogs.54 Reported viral causes of balanoposthitis in dogs are canine herpesvirus (CHVY 21, 23, 49 and, more rarely, calicivirus.12

The predominant clinical sign of balanoposthitis caused by infection with aerobic bacteria or Mycoplasma species in the dog is preputial discharge, which varies in character from purulent , to sanguinopurulent,14,41 The discharge may have a fetid odor.41 The penile and preputial mucosa is erythematous and may be ulcerated or covered with caseous material. Penile lymphoid follicles may be prominent.41 Viral balanoposthitis is characterized by the presence of vesicular or lymphoid nodular lesions on the preputial mucosa and near the preputial reflection on the penis.2, 12, 21, 23, 48 The penile mucosa may be hyperemic, and petechial or submucosal hemorrhage may be presenU,23

Dogs with balanoposthitis as a component of atopic dermatitis may show concurrent pruritus of the feet, ears, and ventrum or may present with excessive licking of the penis as their only sign. The penile and preputial mucosa is erythematous, and penile lymphoid follicles may be prominent. The author is aware of one case of balanoposthitis caused by behavioral self-mutilation; the penile and preputial mucosa was severely erythematous, and the dog had chewed away a portiori. of the ventral surface of the penis.

Diagnosis of balanoposthitis is by visual inspection. Aerobic and Mycoplasma cultures of the preputial and penile mucosa should be performed. Mycoplasma species and many aerobic bacteria, including E. coli, Pasteurella multocida, and l3-hemolytic Streptococcus species are normal flora of the preputial mucosa; thus, culture results should be evaluated with caution.8 CHV is a poor antigen that does not produce long-lasting antibody titers after infection. Definitive diagnosis of CHV requires demonstration of a change in titers in paired serum samples or virus isolation.

Treatment of bacterial or mycoplasmal balan.opo thiti in ludes ad ministration of systemic or topical antibio tics bos I on dtur' nnd sensitivity testing. Enrofloxa in is the nnliilioli(' or clloic(' for Ir(',)llll '111 of Mycoplas1'l'W infc t:ion . nX ( 1 ('~~ iv(' di ~ I< ' h.\I· ~ ', I· iI\(lIlid 1)( ' 1,11'1111\ '(\ frllll) III\" p ni and II'('!'I II'I' h flII H ldll~'1 1111111 ' 1'11 '1"1< '1' 1\1 III WIIIIII Wrl ll"I', Wlilill ~nljn(', (\1 ' lii !IIII 'd lli' l.lcllllI l III ,lilllIll" Itl llllIl 111 111111 1111 Illd.l ll ll l'll 1111 11 11 1'IIII III,d I,v 111 1'1 11 1 " " 1111111 11 11 10 1\ 111 ' 11 1'1 11 1·<1 \ 11 11 cl ltilil ll lllll il lI (I Iii , 1111


costf~roids. Behavioral self-mutilation may be controlled by detecting and eliminating the trigger for the behavior or may require therapy with antianxiety drugs.

Urethral Prolapse

Prolapse of the distal urethra may be idiopathic or may occur secondary to sexual excitement or urethral infection in the dog.n,60 The most common presenting clinical sign is intermittent bleeding from the penis,u, 24, 38, 60 The prolapsed urethral mucosa usually has a pathognomonic "red pea" appearance at the tip of the penis, which allows ready differentiation of urethral prolapse from fracture of the os penis, urethral stricture or calculi, and persistent penile frenulum. 60 The prolapse may occur only when the penis is erect.38 Conservative treatment with tranquilizers, isolation from estrous female dogs or other causes of sexual excitement, cage rest, and antibiotics usually do not effect a cure. Surgical replacement or removal of the prolapsed tissue is the treatment of choice.60 Efficacy of concurrent castration as a means to prevent recurrence is equivoca1.6o Intact dogs with urethral prolapse that respond well to surgical treatment may be used for breeding successfully.u

Fracture of the Os Penis

Fracture of the os penis in the dog is uncommon. Occasionally, the dog may present with a history of known trauma, but the cause is most often unknown.29 Dogs may present with clinical signs either at the time of the fracture or months to years later after nonunion healing of the rrG cture or excessive callus or fibrous tissue formation at the fracture site hfl s exacerbated displacement of fracture fragments or caused urethral obstruction.9, 29, 33, 56, 61 Clinical signs of an acute os penis fracture vary with degree of the fracture (simple or comminuted) and extent of soft I issue injury, and they include obvious ventral deviation of the penis, dysuria and hematuria, pain and crepitus on penile manipulation, disIl' ntion of the urinary bladder, and abdominal pain.29, 30, 56,61 Clinical , ign referable to excessive callus or fibrous tissue formation at the site of fl h aled os perils fracture include dysuria, distention of the urinary bl.ldd r, and ventral deviation of the penis?' 9, 33, 61 Postrenal azotemia 11111 he PI' 'S 'nl: s condary to urin ary tract obstruction.9, 41 Definitive di llg ll (ls is o( rra lure of I·h · os I ' ni s i ~ by rad io raphy.9, 29, 63 Treatment Iii : 11I'~ 'l i r r d r(·du cli!lIl o ( III(' (1'1Iv l II 1'(' ,

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256 ROOT KUSTRITZ

recognizing that the penis is a well-vascularized tissue. With deep penile lacerations, reconstructive surgery or penile amputation may be required if cavernous tissue spaces have been invaded.

Penile Neoplasia

The most common penile neoplasm worldwide is the transmissible venereal tumor (TVT).36,41 Other penile neoplasms described include squamous cell carcinoma of the penile or preputial mucosa, squamous cell carcinoma of the penile urethral mucosa, malignant mast cell tumor of the penis, and chondrosarcoma of the os penis.45,64 Preliminary diagnosis is by visual inspection; definitive diagnosis requires biopsy or conclusive cytology. Treatment options for TVT include surgical removal of the mass; if the mass is inoperable or surgery is undesirable, chemotherapy with vincristine alone or in combination with cyclophosphamide and methotrexate has been reported as a successful treatment for TVT as have radiation therapy and cryotherapy. Therapeutic options for other types of penile neoplasia depend on the tumor type and location.

References

1. Ader PL, Hobson HP: Hypospadias: A review of the veterinary literature and a report of three cases in the dog. J Am Anim Hosp Assoc 14:721, 1978

2. Anvik JO: Clinical considerations of canine herpesvirus infection. Vet Med (Praha) 86:394, 1991

3. Arver S, Sjostrand NO: Functions of adrenergic and cholinergic nerves in canine effectors of seminal emission. Acta Physiol Scand 115:67, 1982

4. Axelson RD: Pseudohermaphroditism in a dog. JAVMA 172:584,1978 5. Balke J: Persistent penile frenulum in a Cocker Spaniel. Vet Med ' Small Anim Clin

76:988, 1981 6. Belkin PB: Persistence of penile frenulum in a dog. Mod Vet Pract 50:80, 1969 7. Bennett D, Baughan J, Murphy F: Wedge osteotomy of the os penis to correct penile

deviation. J Small Anim Pract 27:379, 1986 8. Bjurstrom L, Linde-Forsberg C: Long-term study of aerobic bacteria of the genital tract

in stud dogs. Am J Vet Res 53:670, 1992 9. Bradley RL: Complete urethral obstruction secondary to fracture of the os p enis in a

dog. Compend Contin Educ Pract Vet 7:759, 1985 10. Carati CJ, Creed KE, Keogh EJ: Vascular changes during penile erection in the d og. J

Physiol (Lond) 400:75, 1988 11. Copland MD: Prolapse of the penile urethra in a dog. NZ Vet J 23:180, 1975 12. Crandall RA: Isolation and characterization of caliciviruses from dogs w ith ves icul a r

, genital disease. Arch Virol 98:65, 1988 13. Croshaw JE, Brodey RS: Failure of preputia l cl osure in a d og. JtWM A '1' 6:45(), 1960 14. Doig PA, Ruhnke HL, Bosu WTK: The geni ta l 111 co pl l" 111 11 Il nd III 'I'n p l n ~m ,l 1"1111'11 Dr

healthy and diseased dogs. (l 11 adiiln JOlirillllll r CIl l1IP,II'li llvl' M"d l .. i lll ' 11!'i: :1,, 1<) 11 1 15. Elkins AD: a nin ' 1 (1 1'01 hlmOfl lH o r Ilil il I1tl Wll l' lllI llI)W' A "lill i' 1'1'1" 11'1. VI ' I Mild (1' ,'1111 ,,)

79:638, '191\11, 'l(i. liv ll l1 H Ill i, C' 1t 1'l ,, 1i '11I1t '11 1;1 ' 'I'll. ' 1I 11 1}',1 ' , il lliI 1\'111' 111 11/ 1' \· " ,11 III ' (" tI ) tvl 11 ,'1'1 1\ " ,, 111111 \'

Il l' 111I' I III)'. 1'111 11111 ,, 11 ,111 11, WII' I II II II I Jl I ~ 1'111 I I' " , I 1'1 1:"11 ,, ,,1 WI , 11111\ \' I ll ' 11 111111 1 111' 11 111 1" ,, 11 111111111 11111" ," 111111 \ 11111 111 11' 11 '111 1'


and priapism associated with multifocal distemper encephalomyelitis in a dog. JAVMA 197:90, 1990

18. Gunn-Moore DA, Brown DJ, Holt PE, et all Priapism in seven cats. J Small Anim Pract 36:262, 1995

19. Gunzel-Apel A-R,. S~hne~ C, Krause D: Investigations of ejaculatory processes in the dog after admInistration of an a-receptor blocking agent. J Reprod Fertil Suppl 39:328, 1989

2? Grandage J: The ere~t dog penis: A paradox of flexible rigidity. Vet Rec 91:141, 1972 21. Hashimoto A, Hirai K: Canme herpesvirus infection. In Morrow DA (ed): Current

Therapy in Th~riogenology. Philadelphia, WB Saunders, 1986, p 516 22. Hayes HM, Wilson GP: Hospital incidence of hypospadias in dogs in North America.

Vet Rec 118:605, 1986 23. Hill H, Mare CJ: Genital disease in dogs caused by canine herpesvirus. Am J Vet Res

35:669, 1974 24. Hobson HP, Heller RA: Surgical correction of prolapse of the male urethra. Vet Med

Small Anim Clin 66:1177, 1971 25. Howard PE, Bjorling DE: The intersexual animal: Associated problems. Probl Vet Med

1:74, 1989 26. Hutchison JA: Persistence of the penile frenulum in dogs. Can Vet J 14:71, 1973 27. Jacobs D, Baughman GL: Preputial defect in a puppy. Mod Vet Pract 58:522, 1977 28. Janza. F, ~zemeredi G, Szenci 0, et al: Aetiological studies and therapy of genital

mfection m male dogs. Magyar Allatorvosok Lapja 43:733, 1988 29. Jeffery KL: Fracture of the os penis in a dog. J Am Anim Hosp Assoc 10:41, 1974 :10. Johnston DE: Repairing lesions of the canine penis and prepuce. Mod Vet Pract

46:39,1965 • I. Johnston SD, Bailie NC, Hayden DW, et all Diphallia in a mixed-breed dog with

m ultiple anomalies. Theriogenology 31:1253, 1989 :12. Joshua JO: Persistence of the penile frenulum in a dog. Vet Rec 74:1550, 1962 :13. Kelly SE, Clark WT: Surgical repair of fracture of the os penis in a dog. J Small Anim

Pract 36:507, 1995 :14. Laszlo Z, Laszlo S, Thuroczy J, et all Isolation of mycoplasmas from the genital organs

of healthy dogs and from those showing reproductive failures. Magyar Allatrovosok Lap ja 48:356, 1993

:lfi. Lee J: Paraphimosis in a pseudohermaphrodite dog. Vet Med Small Anim Clin 71:1076, 1976

,16. Mad ewell B~, Theil~n GH: Tumors of the urogenital tract. In Veterinary Cancer Medlcme. Philadelphia, Lea & Febiger, 1987, p 567

\'7. Mantri MB, Vishwasrao SV: Pseudo-hermaphroditism in a German Shepherd dog-A ase report. Indian J Vet Surg 15:98, 1994

,Ill . McDonald RK: Urethral prolapse in a Yorkshire Terrier. Compend Contin Educ Pract V t 11:682, 1989

III , M yers-Wallen VN: Clinical approach to infertile male dogs with sperm in the ejacu-la t '. Ve t Clin North Am Small Anim Pract 21:609, 1991

dO, Mis k NA, A h med IH, Ismail SF: Os penis in dogs. Assiut Vet Med 35:115, 1996 II. N? "·ltLi. : Le 1011S of the canine penis and prepuce. Mod Vet Pract 60:712,1979 I'J, N: I OI;n 'Y<l J I, r:ra i<mn ma T, Niizuma I, et all Penile vascular system of the dog. An

1'1je ' II On-co rroSlO n an d histological s tudy. Jpn J Vet Sci 51:765,1989 d I, t ,) IHOn I' N, Wri ~J y RH., Thrall NA, e t a1: Disorders of the canine prostate gland:

I I"IJ \lgl' lI t'H IH, d18gnOH1R, a n I 111 'd l , I th ·rapy. Compend Contin Educ Pract Vet 9:613 1 ~7 '

1,1. ( )I'I 11I 11 II , ' 1l1l 11 :~ lIi ' I ~ Wnl l '1; ,'I ItI : SIII')\ Il'll 1 Irl' lIlll'le nl o f I ri np is l11 obs rved in a dog III \d ,I I 'II L 11 \11 1 Vl'I .ol'i ti l :1 .'// IIiIN

1' 1 1'11 11 1111 " 1\ 1 I 1\11 ,,,111 111 11'11 1 1' 1 ~ Y.llwl ,. I )1\ : ' I VII ,'11111 '/1 \If 1'1,,, illl' 111' 11 111' Iw o pl nAI1l : , q Lln-111111 1/1 ,',·11 "111, 1'1 11 11 111 ,,, "l '''!'IIi 'II I·lt VI,, " 1 1'IIII"tll 'litl llI"'11I 11,1 , I 1\ '1 1 1\ 111 111 1i0li P I\ H,'I(11' 'd:oI l1, I, 11"111

If I 1'1 " 11 1" ' 1',1111 'I \AI 11 11 I 'll I l tv! I " \' Id ,, " 111 .1 111 111 ' " 11 1 " " ,111'.1 .1 1'1", Iii III " ' 1/ \11 /11""1 " 11111 1111 \11111 11 11 1,11 11 11 11,' W Iii 111 11 11 11'111 111\ 111 \1' I I' tI / 111'1,

258 ROOT KUSTRITZ

47. Post K, Barth AD, Kiefer UT, et al: Retrograde ejaculation in a Shetland sheepdog. Can Vet J 33:53, 1992

48. Poste G, King N: Isolation of a herpesvirus from the canine genital tract: Association with infertility, abortion and stillbirths. Vet Rec 88:229, 1971

49. Potena A, Greco G, Lorizio R: Su di una rarissima difallia in un cane. Acta Med Vet 20:125, 1974

50. Proescholdt TA, DeYoung DW, Evans LE: Preputial reconstruction for phimosis and infantile penis. J Am Anim Hosp Assoc 13:725, 1977

51. Purswell BJ: Pharmaceuticals used in canine reproduction. Semin Vet Med Surg 9:54, 1994

52. Root MV, Johnston SD, Olson PN: Concurrent retrograde ejaculation and hypothyroidism in a dog: Case report. Theriogenology 41:593, 1994

53. Root Kustritz MV, Olson PN: Theriogenology question of the month [idiopathic priapism in a dog]. JAVMA 214:1483, 1999

54. Rosendal S: Canine mycoplasmas: Their ecologic niche and role in disease. JAVMA 180:1212, 1982

55. Ryer KA: Persistent penile frenulum in a Cocker SpanieL Vet Med Small Anim Clin 74:688, 1979

56. Ryer KA: What is your diagnosis? [Fracture of the os penis in a dog]. JAVMA 177:177, 1980

57. Sahay PN, Dass LL, Mukherjee R, et al: Phallocampsis due to p~rsistent frenulum in a dog. Indian Vet J 64:524, 1987

58. Salmeri KR, Bloomberg MS, Scruggs SL, et al: Gonadectomy in immature dogs: Effects on skeletal, physical, and behavioral development. JAVMA 198:1193, 1991

59. Singh M, Singh D, Mathur BB: Surgical management of paraphimosis in a cryptorchid dog. Indian J Vet Surg 2:36, 1981

60. Sinibaldi KR, Green RW: Surgical correction of prolapse of the male urethra in three English Bulldogs. J Am Anim Hosp Assoc 9:450, 1973

61. Stead AC: Fracture of the os penis in the dog-Two case reports. J Small Anim Pract 13:19,1972

62. Thomas AJ: Ejaculatory dysfunction. Fertil Steril 39:445, 1983 63. Valji K, Bookstein JJ: The veno-occlusive mechanism of the canine corpus cavemosum:

Angiographic and pharmacologic studies. J Urol 138:1467, 1987 64. Wakui S, Furusato M, Nomura Y, et al: Testicular epidermoid cyst and penile squamous

cell carcinoma in a dog. Vet Pathol 29:543, 1992 65. Wallace MS: The diagnosis of infertility and subfertility secondary to prqstatic disease

in the dog. In Proceedings of the Annual Meeting of the Society for Theriogenology, San Diego, 1991, p 229

66. Winter Cc, McDowell G: Experience with 105 patients with priapism: Update revi,ew of all aspects. J Urol 140:980, 1988

67. Zucker SA, Root MV, Johnston SD: Diphallia and polymelia in a dog. Canine Pract 18:15, 1993

Send reprint reques ts to

Margaret V. Root Kustritz, DVM, PhD Department of Small Animal Clinical Sciences

C339 VTE 1352 Boyd Avenue St Pau l, MN 55108

'-m ni l : 1"(l\l I:kOO'1 tc. 1 1111 11. ·tllI


CLINICAL MANAGEMENT OF THE SUBFERTILE STUD DOG

Joni L. Freshman, DVM, MS

Sub fertility is defined as "the state of being less than normally fertile." This may result from a variety of abnormalities: lack of libido, inability to perform the breeding, and abnormalities of the semen. Subfertility may be suspected if a stud dog fails to produce litters in over 75% of breedings when bred to normal bitches using adequate breeding management protocols.s This situation is frustrating and costly to breed('r~ , who typically have invested a great deal of time and money to jll"oduce, campaign, and advertise their stud dog. Inability to consistently l)f'oduce litters can be terminal for a dog's breeding career.

Evaluation and management of sub fertility begins with identifying (h • stage of breeding wherein the problem exists. Further diagnostics dnd management are based on this underlying identification.

LACK OF LIBIDO BUT NORMAL EJACULATE

Libido may be subnormal or completely lacking. A complete history Ilould be obtained, with particular attention to the dog's breeding

I' pCl" ience and how his sexual behavior during puberty was managed. ( )( )gs that are harshly disciplined for inappropriate mounting may later I' hib it a lack of libido in desired breeding situations. With a specific 11(% li bido m.ay either be enhanced or inhibited by the owner's presence. ~: () 11l C log have pronounced mate preferences.23 These dogs can have '11'1 1)('1) 0 11 · ted LI ' in a preferred teaser; the chosen bitch is then artifi-1 I. il ly insul11 inut -d . Rstrus wab that have been previously frozen and

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260 FRESHMAN

thawed for use can provide the scent cue when applied to or held near the teaser's vulva.

Young or aged dogs may have inadequate libido. Underlying medical conditions that affect the dog's energy level and attitude can produce a secondary lack of libido. A complete blood cell count (CBC): bioche~istry profile, and urinalysis should be performed for s~r~enmg of d~seases. Because hypothyroidism can produce a lack of lIbIdo, a thyroId profile to include free T4 by equilibrium ~ial'y~is and canine thyro.idstimulating hormone should be evaluated. DImInIshed olfactory functIOn may inhibit libido by altering the dog's perception of pheromones. Canine parainfluenza virus has been shown to negatively affect olfactory functionP Return to normal function ultimately occurs.

Some dogs require repeated exposures to positive breeding situations with willing estrous bitches to exhibit normal libido. Some dogs may be reassured by having the bitch manually restrained, alth?ugh others prefer a minimum of human assistance. An adverse expenence such as being bitten in a first breeding exposure may have serious effects on a dog's libido. Anecdotally, gonadotropin-releasing' hormone (GnRH) injections can be given to increase libido.16 This stimulates luteinizing hormone (LH) release from the anterior pituitary, which, in turn, causes testosterone release from the Leydig cells in the testes. Injections of GnRH (3.3 /-Lg/kg intramuscularly) are given once weekly for 1 month before breeding.16 Different formulations of GnRH are available, and t~e choice of product is apparently important. In one study, gonadorelin hydrochloride (Factrel; Fort Dodge Animal Health, Fort Dodge, IA) resulted in an initial rise in serum testosterone followed by a 3- to 4-day trend of decreased testosterone, although gonadorelin diacetate tetrahydrate (Cystorelin; Merial, Iselin, NJ) resulted in elevated serum testosterone for 5 days.16 Gonadorelin diacetate tetrahydrate would thus be the preferred product. Testosterone and related androgenic drugs should never be given to a breeding male dog because of their negat~ve feedback effect on the pituitary, resulting in decreased LH productIon and decreased intratesticular testosterone production, leading to decreased sperm production.20

INABLITY TO PERFORM BREEDING BUT NORMAL EJACULATE

Dogs with significant systemic disease or a variety of orthop~dic and neurologic abnormalities may be unable to m ount, thrust, or a In v and maintain intromission. A complete history of any PI' vi o us no 'd i al problems and injuries is imp ortan t. A B, l~ i ()cI~c n iSlry I ro Cil c, n.nd urinalysis are p erform d to v, Ili a lt' for H 101 1('1111< ' <l ira'll. I' . /\ 1) I' hUlI . ll v\, orthopedic and n Ll ro l og i ~ I'vn ill nli,)l l : III HlIti III' 1'1'1'II)I'IIII 'ti , wil h p.lI 'li, · l.l lar a ttention til 11)(' 111 '1 '1, /I11t '1" 1IIId 1'\'1 11' II')', I ,I Ilid 111/ dl 'l,d d 111'1 1/11', s\'ven' 14 1111(111 ), 11 1111: , 1/ "1'," 11"1111 VI' 111111 " 11 ', 111 ' III 1111 ' Idl ll II I ' 111 ,,/, Ili id IIlld llll', llIl/ I.1i ,11 111'11111 ' 11 11 ,11 1' l illI/Ii iI' 1111 ' ,"1 1111 111 11 11I 11 11111I ·dll "1111 ' 1'

CLlNlCAL MANAGEMENT OF THE SUBFERTILE sTUD DOG 261

for inability to breed. Partially protruding intervertebral disks and degenerative myelopathy should be searched for in the neurologic examination. Prostatic disease can cause pain with ejaculation and should be evaluated for by m eans of a rectal examination and prostatic ultrasonography.

Should the underlying orthopedic or neurologic problem not be correctable, semen can be collected with the dog placed in a comfortable standing position, and the semen can be used via artificial insemination. Consideration of the heritability of the underlying condition should be part of the decision with regard to use of the stud dog.

ABNORMALITIES OF THE SEMEN

Semen abnormalities frequently result in sub fertility. To appreciate abnormal semen, it is necessary to be familiar with normal semen quality. Proper collection of semen is necessary to obtain a representative sample to evaluate.

Semen Collection

Before collection, the dog should be allowed and encouraged to 'mpty his bladder, as urine contamination of the semen is detrimental 1'0 motility. The presence of a friendly teaser bitch in estrus is of great h lp in obtaining a complete ejaculate. In lieu of an estrous bitch, a bitch the dog likes is used in conjunction with thawed estrous swabs.

The bitch should be held in a standing position, with the handler on her right, to keep her standing and restrain her head. Ideally, an II ggressive bitch should not be used; if this is unavoidable, a muzzle HI ould be applied. If the dog is nervous or reluctant and the bitch is friendly, they may be allowed to play before collection.

A quiet location with excellent footing is necessary. Ideally, a room I h' dog does not associate with other veterinary procedures is used. If physical examination, venipuncture, or other diagnostics are to be pI' rf nned the sam e day, semen collection should be performed first. I' ~J1'loval of the white laboratory coat or other "doctor" signals can help to Ket th dog at ease. Excellent footing for the dog can be ensured with lil t' 11 :4 of a ru bb r-backed m at of appropriate size. Over time, a mat III ('li fo r t r c ling d 'v lops a c n t that also acts as a cue and stimulant 1M lli l' dog. , (,'m ' 11 frOI1l toy brC'd thnt a r u ed to being bred on a 11 \1/, ' Il UI lWKI l)(' co ll ('clt'd on II ruhlw r-mn lt'd g rooming table. Any l'q ll ipllll ' lll 11 )(' dOl) 01 1-1 , Ild,ll t'1l w illi hn '(·d ing ,' ''ould lw I rOllght by the IIW IIl' I' In 11i ·1" 1'1 , 1,1\ " 'Id I'lli' Ih, ' .1(1 )" . 1,111 11'11 '. 11 11 1)', 1,'lI y (I Y; Itl llll H(111 nnd /11 1111 /11111 ( '11 1111 '1 111 , Nt·w 1IIIi llll Wl, I. , Nil 11 II ld l'I'I'II IIIII \(' IHI, .d , Ill' 1II 'I.d l'tI , .1 111/111', \ ,, 11 "1 11, 111 II I 11 11 ' , '1111 111 1111 ' f\ 11I 1111 \' It! 11 ' 11 \1 '11 II ' 11 1" '1 1I ,Iy 1III "I 'I"d \\'11 /1 1I 1'111 11 111 I lil li" II I I', III 1111 1" , IV III 11 11 ' ,.11 \ II

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262 FRESHMAN

(canine artificial vagina; Synbiotics, San Diego, CA) and clear 15-mL centrifuge tubes. The first tube should have a small hole in the side near the top to prevent vacuum formation. Tubes can be changed between fractions; if this is done, the subsequent tubes do not have vent holes, and the tip of the AV is inserted into the top of the centrifuge tube. For a right-handed collector, the AV is held in the left hand and the cuff is folded over the hand to create the appropriate size AV for the patient. The AV is held at the tip of the prepuce while the right hand massages the penis within the prepuce. As the bulbus glandis begins to enlarge, the AV is pushed up over the penis, pushing the prepuce behind the bulbus glandis. Once in this position, the left hand is held tightly over and behind the bulbus glandis to simulate a tie while the right hand continues to stimulate as needed. Should the bulbus enlarge too quickly to allow the prepuce to be pushed behind it, simply stop the collection process, walk the dog to allow his erection to subside, and begin again. Complete erection and ejaculation with the bulbus inside the prepuce is painful and may result in an incomplete collection a~d dislike of the collection process.

Canine semen is ejaculated in three fractions . The first is a relatively clear presperm fraction, which can be 0.5 to many milliliters in volume. The second sperm-rich fraction is normally milky white and approximately 0.5 to 2 mL in volume. The third prostatic fraction is again normally clear and can be a few to many milliliters in volume depending on the length of time that pressure on the penis is maintained. Aged or insecure dogs may not have easily defined fractionation of their semen. Once semen collection is complete, walk the dog away from the teaser. A cool compress or lubricating jelly placed at the junction of the penis and the prepuce may be helpful to ease retraction of the penis into the prepuce. Care must be taken in long-haired dogs that no hair is wrapped around the penis or trapped inside the prepuce. The dog should not be kenneled or placed with other dogs until his penis is completely back within the prepuce.

Semen Evaluation

Initial evaluation of semen consists of recording the volume and color of each fraction. A yellow color indicates urine contamination, and red blood cells may indicate prostatic disease.

Motility

Motility is immedi atly ass ssvti ~ ()h~('I"vin )', n d rop of seillen, preferably from th spcrm-ril' h fl":1 (' lioll wi lhol ll IlI 'O:: lldll ' 1III Id I'()llldild nation, pIa 'd on [) . 7"(' WIII'II)('tI II d t', ( ' \I V' 'I" ,Ii w illi II I '(lVI'I'H111" ,llld

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CLINICAL MANAGEMENT OF THE SUBFERTILE STUD DOG 263

buffered saline (7.5 pH) to allow visualization of motility. Normal semen should show at least 70% progressive motility, with spermatozoa moving rapidly across the field of view.18 Normal spermatozoa maintain motility for hours; rapid loss of motility is associated with poor fertility.4 Serial evaluation of motility can be performed by repeating this procedure at varied time intervals.

Concentration

Concentration of spermatozoa is measured with the use of a hemocytometer and a Unopette (Becton-Dickinson, Rutherford, NJ) counting system for white blood cells.18 The sperm-rich fraction is gently agitated and then drawn into the Unopette capillary tube (0.02 mL), dispensed into a diluent chamber (1.98 mL), and mixed. The diluent-semen mixture is loaded into the hemocytometer and allowed to settle for a few minutes. Because the spermatozoa are no longer motile, they are readily counted. The number of spermatozoa in one of the nine primary squares in the hemocytometer grid is counted. Counting and averaging the spermatozoa in three squares can improve accuracy. This number equals the number of spermatozoa in millions per milliliter of semen. This number is multiplied by the total milliliters of sperm-rich fraction collected to give the total spermatozoa in the ejaculate. On average, a dog should have at least 250 million spermatozoa in the ejaculate, although this number can be several billion.18 Various factors may affect the number of spermatozoa per ejaculate, including age, degree of arousal, testicular size, and frequency of ejaculation. The number of spermatozoa produced by a normal dog is directly related to the weight of the testes.3

This, in turn, can be estimated by measuring total scrotal width (TSW). This can be performed using calipers, pressing the testes down into the s ' rotum, and holding them parallel to each other without altering their shape. Three to five measurements are taken and averaged; the testes should be repositioned between each measuremenP As a general rule, lIormal dogs with a body weight of 10 to 34 Ib should have a TSW of Ilpproximately 36 mm, dogs with a body weight of 35 to 39 Ib should have a TSW of approximately 50 mm, and dogs with a body weight of ( () to 84 lb should have a TSW of approximately 56 mm.3 Toy-breed dog ' m y hay normal ejaculates with less than 250 million spermato!',on. I og with less than 200 million spermatozoa per ejaculate after Ht·Xllf.l l resl' may b subfertile when used for breedingY Total scrotal circumference nn b tn asured Similarly with a tape measure to monitor .1 111 1 for a Irl'llll of dC('I"('8s ing t 'sl'iular s ize, whi.ch may be associated wi lli "q~( ' I h'n li vl' prot' .. ,' l" '.

1'1'1 ' ,\11 ( ' 11 1' Il l' ('i.l clll ril ioli ,11'1'1 '1'1. Ihl' Iltllnhvl' or Hp el'rn 8t07.0fi in th 1'/,, 1',11 ,111 ' , III d O)',1 1'1'11 111 wld,' 11 It'll 11'1 I 1/ l'OIl I' I' It'd d,li l , 11ll' Illlilliw l' or 1'1'1 ' 1'111 11111 '1,( 111 III lil (· 1'1111" ,11 ('1'111 " V ill i /1 "11j1l '1l 1I1 1!I , ' ly '.111% 1(,IItI Ihnil

11 11 1 I ' II lill y II ' 111 ,d (I, '/ tI ,IV ) d" f', I Wil li 11111 1'. 111( ' l l' lil ll III'i W(\(' 11 (' /111 '111 11 11t1l1 , 1/11 ' j\ 111 11 \' 111 dll( Ir 11'111 1111111 11 "11. Ititl"1 ' 1'1' 111 11 1111 ( 11 1 ( 11 1' 1' 1II ,II(.d III IIII' 1111111 ' , I III " 1(.11" 1 111111 lOll • " "' II I 1111 - III 11 11 I ' I 11 11 11 1((11111 tl l llI \

264 FRESHMAN

sperm output; this is what the dog produces on a daily basis and is over 80% correlated with body weight in a normal dog.3 Determination of daily sperm output may be helpful in a heavily used stud dog to determine the frequency of breeding that still provides an adequate concentration of spermatozoa. Healthy dogs caged in new surroundings may show a transitory drop in spermatozoa per ejaculate, possibly a result of the adverse effect of increased endogenous glucocorticoid secretion.4 This seems to be reversed after 6 months.4

Dogs with good ejaculatory behavior but no sperm in the ejaculate should be evaluated for retrograde ejaculation. This can be done by collecting urine before and after ejaculation and examining it ~nd.e~ the microscope with the condenser on low for the presence of a sIgruficant number of spermatozoa in the postsample ejaculate as compared with the presample ejaculate.

Morphology

Semen morphology is evaluated by placing a drop of eosin-nigrosin stain on a glass slide, adding a drop of semen, smearing the drops, and examining the stained semen at X 100 magnification under oiU8

Alternatively, a Wright-Giemsa type stain can be used (Harle co Hemacolor; EM Diagnostic Systems, Gibbstown, NJ).19 One hundred sperm are evaluated for primary and secondary defects (Table 1). Primary defects represent abnormalities in formation of the sper~atozoa and ~re consi~ered more serious than secondary defects, whIch occur durmg transIt through the ductal system, collection, or processing of the semen. Dogs that have been sexually rested for over 10 days may have an increase in detached heads and distal droplets as a result of prolonged storage.14

Secondary defects may also result from trauma or glucocorticoid administration.7

Normal semen should have at least 70% morphologically normal spermatozoa.4 Abnormal morphology greater than 2?% can result in subfertility.4 Calculating the total number of morphologIcally normal and motile sperm per ejaculate can assist the clinician in assessing fertility.

Table 1. SPERMATOZOAL DEFECTS

Primary

Abnormal head shape Abnormal mid piece

Double Swollen

Coiled ta il DO~lhl C" I'n il l'roxinlll l l 'y ll ll"" l lI l iI. "" 'I<iI'1

Secondary

Detached heads Bent mi Ipic ' Bonl I:n il l ) i:41111 ,'y l()p ldHlll k "" 01'1"1 I{,' II II I /It'd 11\ I t 1111 11111 1


Additional Evaluation

The number of white blood cells in the semen can also be determined using a hemocytometer and Unopette .system: The count s~ould be performed on the sperm-rich and prostatic fractIOns. To obtam the count, white blood cells are counted in the four corner primary squares of the hemocytometer and the total number is multiplied by 250 to equal the number of white blood cells per cubic millimeter.13 Normal values are less than or equal to 2000 per cubic millimeter.

The pH of each fraction can be measured with pH tape. Normal pH is 6.3 to 6.7.7 A drop of semen should be pipetted from the sample onto lhe pH tape, because inunersion of pH tape into the sample may adversely affect motility.

Cytology of each fraction should be evaluated using a smeared drop stained with a Wright-Giemsa rapid stain. The presence of red blood cells, epithelial cells, or any other abnormalities should be recorded:

No dog should be diagnosed with abnormal semen on the baSIS of f1 Single collection. Multiple collections on different days may be needed 10 obtain an accurate assessment of a dog's semen quality.

Management of Dogs with Abnormal Semen

Depending on the underlying cause of the problem, many dogs with abnormal semen can be successfully used for breeding. An effort 'i1 ould be made to determine and correct underlying causes. Additional d iagnostics appropriate for this e.valuat~on ,include a C~C; chemistry profile; urinalysis (including after ejaculation m azoospermIc dogs); prosIo\ ti c ultrasonography; cultures of semen and prostatic samples for bacterin, Mycoplasma, and Ureaplasma; and hormonal evaluation.

M dication and Environment

1\ number of drugs can affect spermatozoal production and reproII (Ictive function, including prednisone, betamethasone, methyltestoster-111$', imetidine, clomipramine, and ketoconazole.9, 19 These drugs sh~uld 1)(' el iminated, and semen should be evaluated 3 months after cessation. VI' I(' rina rian working with stud dogs should use caution in administerIll)' m 'd i a li on to th e dogs, Testicular degeneration can occur secondI II ' I In (' l1vironm ntal temperature (e.g., dog sitting on hot surface), III'I IV III ,till s, ml'r uria l ompounds, and other toxins.2 The owner ,llllI ild Iw qUl'. ' lioncd <1 bout [he dog's hOllsing and any environmental III ill: lit,11 ('(lIild lw pres(' l)[ I Vl'.lll. 'l' of Inndfills, h mical plants, well w I I I ' I ~ $ 1' (l ili l' !' ilulil slri,iI J1 () llllI ll nl ~.

111 111 11 )',11 111'011', 11' 1,111 ' 1' 111 11' 11 11 1 ,iI II 1111111 11 1' 101 111',1', lil l '\' 1\',1111 I IllI illll i' 1, ·\, ,·1 I ii 1" ' 11 1111111 1111 111 ' \ I Jill 11 111 \1' tI I I, I II 111 11 1111 11111 I tl ' 11',1' I

266 FRESHMAN

Large- or giant-breed dogs may reasonably reach this level at an older age. For a young sub fertile dog with no other problems, time may be the best treatment.

Testicular degeneration also occurs with age. Senile atrophy is unlikely to respond to treatment. Older dogs with low sperm numbers are best managed by conserving their spermatozoal reserves. Bitches to be bred should undergo accurate ovulation timing. Insertion of the semen directly into the uterus using a surgical or transcervical technique may also be indicated in cases with low numbers or poor motility.

Retrograde Ejaculation

Male dogs that are azoospermic but have a large number of spermatozoa in the postejaculate urine can be treated successfully. At 1 and 3 hours before collection or breeding, they are given pseudoephedrine (4 mg/kg orally).15

Testicular Hypoplasia

Although no experimental data have been published, anecdot~l reports indicate that gonadotropins may be helpful as symptomatic treatment. Human chorionic gonadotropin (hCG; 500 IU subcutaneously) is given twice weekly.2 Caution is indicated in the use of hCG; in other species, abnormal testicular steroidogenesis has been present for 10 days after injection.3 GnRH (125-250 ng/kg) may be tried in place of hCG.3 Testosterone or other anabolic steroids should not be used for reasons previously noted.

Normal endocrine function can be evaluated using a GnRH stimulation test. GnRH is given (1 J.Lg/lb intravenously), and samples are taken immediately and 1 to 3 hours later.I,B Baseline serum testosterone values are 0.4 to 10 ng/mL (average, 1-4 ng/mL), with a 100% increase after stimulation in a normal male dog.l Serum testosterone and LH values can be measured via the GnRH stimulation test; because of their episodic release, resting levels are quite variable.3

Prostatic Disease

Approximately 80% of intact male dogs over the age of 5 years h ave some level of benign prostatic hypertrophy or hyperplasia. Thi incr ases

, the risk of prostatic infection, particularly chronic p rostatitis. M~ny d~ with chronic prostatitis exhibit no overt clinical igns; how 'v ' r, Inf ' tlo n in the prostate readily extend to th p id id rniti <'s nnd I l'S tt ,S ." Nor11lfl l prostatic fluid tran sp o rts sp rmnto:t;oCl fi nd ,' I iJ III iI (I 1(", HI ll" 1"11\11l 0 Y. ll, d I) )()tility. Abnorm al Fro, lil li e flllid ('I II) .. d vl'rfll 'ly IJlII '!'1 !ll ll lilily: ' II, I!'I!) I", inv o lv(1 I in Ih (" i1 d v l 'l'~ iI ' ,,1'1 1·, '1 111 1 1111 11 II 111\ 111 .1. , .11'1'1'1'1 1 •• d 1111 1\ 1 H·,'I'I' li lln, illt ' I'I 'IIH'" 1I " 'II1I.1 I1 I \, il l ' I I 'I 1/ 1I1 1'1!1 ' II I I.l I Il IlIi I , 111 1' 11 ' l lil ' lll l h l, 'I I ' ll n ,

01 11.11 '" ' 1\ '1 1"" I ii 1111111'111 11111 111111 ,111\111 111 111 \ .1. ,1'111" '11\1' 111111t .11 111" 1' 1"1)1 1 '


sees older dogs with spermatozoa that have poor initial motility or normal motility with rapid deterioration secondary to chronic prostatitis.

Diagnosis of chronic prostatitis is best made by a combination of semen evaluation, urinalysis, cultures of prostatic samples, prostatic ultrasound, and possibly fine needle aspiration or biopsy. Semen evaluation often reveals abnormal motility, an increased number of white blood cells, epithelial cells, and increased secondary defects. Results of a CBC are usually normal. Bacterial cystitis is a common finding.

Various opinions exist on the ideal method for obtaining accurate material for culturing of the prostate, One method is to collect an ejaculate as previously described and then to collect a small amount of prostatic fluid directly into a sterile vial for culturing. IS The sample ~hould be submitted in appropriate m edia and in a timely manner for detection of bacteria, Mycoplasma, and Ureaplasma. Bacteria and Mycoplasma may be p resent in the urethra of a normal dog. Greater than 105

olony-forming units per milliliter or heavy growth of a single organism from a sample with an increased number of white blood cells is suggestive of infection.21 Alternatively, fine needle aspirates or tissue biopsies of the prostate can be submitted for culturing. Quantitative cultures of the semen and urethra can be performed. A greater than 3 log increase in the number of bacteria isolated from the semen as compared with the II rethra indicates a significant infection as opposed to normal flora .

Treatment of chronic prostatitis in an intact male dog is a long-term process . Antibiotics should be chosen based on their ability to penetrate into the prostate and the pH of prostatic fluid as well as on sensitivity Il'sting. The pH of the blood and interstitium is 7.4, and that of the 110rmal prostate is acidic.6 This can change with infection, but in the ,HI thor 's experience, most dogs with chronic prostatitis have acidic prosl.1l ic pH. Good antibiotic choices for acidic pH include erythromycin oI nd trimethoprim-sulfa combinations.6 Trimethoprim-sulfa combinations ,I\, ' not an ideal choice for long-term use because of the risk of keratocon-11111 tivitis sicca and polyarthritis. Frequent m onitoring of tear production IS indicated if this drug is used. Chloramphenicol and fluoroquinolones " I'l' good ch oices because they penetrate the prostate well regardless of pi 1." Fluoroquinolones are commonly used because of their excellent Ill'Os ta ti p en etration and spectrum of activ ity. Appropriate antibiotics ' ilo u ld b g iv n for 6 to 9 weeks, and the p rostate should then be I'pn tllu r d w itho u t cessation of antibioticsY Mean duration of antibiotic 1I\I'I'il py to on troJbronic b acterial p rostatitis in intact dogs is 9.5 wl'I'b; ." On " I'hl' inf ' ti on is controlled, long-term low-dose antibiotic Ihl' I'. )1' i,' in ilinl.l' I w il'h one thi rd of th tota l d aily therapeutic dose 1',1 ,' II in Il l\' ('ve il ing ufll ' l' voidi ng ,l) This is conlinued for at lea t 6 to I I Il\Jl lilli H, III Il il l ,! IIIIH) I"" (1' 111'1'11'1)('(', long l(' rn low-dose th ' rapy i 1>1 1"11 1'I'Ipdl'C'd 111 1' I l l1' 1'1 '111 .1 Ih ll'l' 0111 11 ' do)'. ' illlll\'l lil'l ' 10 Il Hl inl'n in

• ' 1\ )1 '1 I tj II , " II II ILIII I ' 1"1' 111111 I II II~ 111 ' 1l" lldl ll 11 d ll)',' \ 111 1 1111111 '111 ' 11 110 11 11 /,11,"

111. ,1 1111\ l il li / lId 11\ 1111 1 111 111 I III "1' 11 111 1' 1111 ' 1" '111 11 11 1'1 1.1 111 111 1 11 11 ' 1"11 !.lI ll 1111 01 I )11 11 11 1', 1,, 11 "1 11111 1 " II " ,1111 111 11 I,, · 111 1, II 111'11 11 ,·, I II 111 11.,

268 FRESHMAN

of the prostatic fluid as possible. The sperm-rich fraction is then gently layered on top of 1 mL of a semen-separating solution (Semen Separating Solution; Synbiotics, San Diego, CA) and centrifuged at low speed (100-50 G) for 5 minutes in a round-bottomed centrifuge tube. Most of the supernatant is carefully removed and discarded. The remaining soft pellet of spermatozoa is resuspended in the small amount of supernatant, and a semen buffer (for fresh or chilled semen; Synbiotics) is added at a 1:2 to 1:4 ratio depending on the concentration of spermatozoa and the method of insemination. This frequently results in improved and prolonged motility in vitro; similar results are anticipated in vivo, but controlled studies have not been performed.

SUMMARY

Many subfertile stud dogs can sire pups with appropriate management. Determination of the area of the problem (libido, ability to breed, semen quality) is the first step. Each of these areas can often be improved or managed. A complete history, physical examination, and semen evaluation should be performed on every patient. In specific cases, additional diagnostics may be helpful, including a CBC, biochemistry profile, urinalysis, semen cultures, ultrasonography, and biopsy. Management of breeding, including ovulation timing and intrauterine insemination, can be vital in dogs with low spermatozoal numbers or motility.

Treatment of underlying prostatic disease can dramatically improve semen quality and fertility.

References

1. Amann RP: Reproductive physiology and endocrinology of the dog. In Morrow D (ed): Current Therapy in Theriogenology 2. Philadelphia, WB Saunders, 1986, p 532

2. Barsanti I, Finco D: Canine prostatic diseases. In Morrow D (ed): Current Therapy in Theriogenology 2. Philadelphia, WB Saunders, 1986, p 544

3. Beach FA: Coital behavior in dogs: 8. Social affinity, dominance and sexual preference in the bitch. Behavior 36:131, 1970

4. Cowan LA, Barsanti JA, Corwell W, et al: Effects of castration on chronic bacterial prostatitis in dogs. JAVMA 199:3, 1991

5. Dorland's Illustrated Medical Dictionary, ed 25. Philadelphia, WB Saunders 1974, p 1487

6. Eilts BE: The canine breeding soundness examination form: Its practical role in your clinic. In American College of Theriogenology and Society for Theriogenology, Proceedings of Canine Male Symposium, Montreal, Canada, ] 997, p 37

7. Fayrer-Hoskin R, Smith F: Infertility, male-dogs. (II Til l Y LP, l1lith FW ( Is): '1'11(' 5 Minute Veterinary Consult Canine and Fl in . l3o llil1lo l'L', Wi lli :lIIlH & Will in H, 1997, p 90

8. Feldman Ee, Nlson RW: linicnl 11 1111 .i illr, llI lllI h' " Vl d'l il llil ll " I III" lli .d,· I'1' jll'IHhl l'il vl' tract. In anine And IIl,lIlll' 1': lld 'II 'I'llllli lll 'ol' iliid 1{I'IIII ,dlll 'II" " , ".I ' I l'ldl lld l·lldllll , WII

Dl lI1d\'I'H, 1'1'16, J11' 1t7 \ (,1 10 II, 1I" I'li lllll,l'III ' I 111I}',I1 1111 1" 11 111', 1'<11 1111 , 11\ lit , l' I,d, .IIII'. 1/1 1 111 ("d) \ " " 'III V,'II< I 111 ,11 I'

'1'111'1 11 1 ' I' 1'ldlll'! " lloI l1l1 lV II ' "Ililll l, I 1"" '1 I' I ' ' I


10. Freshman JL: Effects of drugs and environmental agents on fertility in the stud dog. In Society for Theriogenology Proceedings of the Annual Meeting, San Diego, 1991, p 226

n , Freshman JL, Amann RA, Soderberg SF: Clinical evaluation of infertility in dogs. Compend Contin Educ Pract Vet 10:4, 1988

]2. Freshman JL, Olson PN, Amann RP, et al: The effects of methyltestosterone in male greyhounds. Theriogenology 33, 1990

13. Johnston SD: Performing a complete canine semen evaluation in a small animal hospitaL Vet Clin North Am Small Anim Pract 21:3, 1991

14. Johnston SD: Reproduction case workups in the male dog and cat. In Society for Theriogenology Proceedings of the Annual Meeting, Kansas City, 1994, P 190

15. Larsen, R: Testicular degeneration and hypoplasia. In Tilley LP, Smith FW (eds): The 5 Minute Veterinary Consult Canine and Feline. Baltimore, Williams & Wilkins, 1997, p 1094

16. Ling GV: Diagnosis and medical management of prostatic infections in dogs. In Society for Theriogenology, Proceedings of the Annual Meeting, Toronto, 1990, p 255

17. Meyers-Wallen V: Clinical approach to infertile male dogs with sperm in the ejaculate. Vet Clin North Am Small Anim Pract 21:3,1991

I . Meyers-Wallen V: Diagnostic approach to infertility in the stud dog. In Society for Theriogenology, Proceedings of the Annual Meeting, Coeur d 'Alene, 1989, p 327

19. Myers LI, Nusbaum KE, Swango LI, et al: Dysfunction of sense of smell caused by canine parainfluenza virus infection in dogs. Am J Vet Res 49, 1988, P 188

2(). Purswell BJ: Pharmaceuticals used in canine theriogenology. In Society for Theriogenology, Proceedings of the Annual Meeting, Baltimore, 1998, p 92

21. Purswell BI, Wilcke JR: Use of GnRH in the intact male dog. In Society for Theriogenology, Proceedings of the Annual Meeting, San Antonio, 1992, p 140

21, Soderberg S: Infertility in the male dog. In Morrow D (ed): Current Therapy in Theriogenology 2. Philadelphia, WB Saunders, 1986, p 544

2. . Wallace MS: The diagnosis of infertility and subfertility secondary to prostatic disease In the dog. In Society for Theriogenology, Proceedings of the Annual Meeting, San Diego, 1991, p 229


Joni L. Freshman, DVM, MS Canine Consultations

3060 Woodview Court Colorado Springs, CO 80918

CLINlCAL THERIOGENOLOGY 0195-5616/01 $15,00 + ,00

SURGERY OF THE CANINE VAGINA AND VULVA

Kyle G. Mathews, DVM, MS

Surgically treatable conditions of the canine vagina and vulva have n biphasic age distribution. Conditions that primarily affect younger dogs include perivulvar dermatitis, rectovaginal fistula, anovulvar cleft, vaginal edema or prolapse, and vaginal stenosis or stricture. Older dogs ,1 re primarily presented for diagnosis and treatment of vaginal neoplasia. Surgical management of these conditions often results in resolution of clinical signs and can be simple or extremely complex. This article d 'scribes the approaches and specific techniques required for management of these conditions.

SURGICAL APPROACHES TO THE CANINE VAGINA

Most vaginal surgeries are performed via a caudal approach. EpisiI,[omy is frequently required to improve exposure of vaginal or vestibu-1.11' abnormalities. The caudal approach to the vagina requires the followIi 19 preparatory steps:

1. Consideration should be given to placement of a transdermal fentanyl patch or epidural anesthesia. IS If elected, an appropriately sized fentanyl patch (4 /-Lg/kg/h) should be applied the day before surgery.

2. A purse-string suture (2-0 to 3-0 nylon) is placed around the anus to prevent intraoperative fecal contamination. A sign (white tape) is placed on the dog's head with the words "purse-string" clearly v.i s i.bl (Fig. 1). This is to remind the surgeon and anesthetist to

Jilll ll\ II I\' 1)"I ' III'II\1I' ,I( of' (, lll1i ('1I 1 ,'d,'<1e('II, 'oll !')\l' or V"i('l'ina I'Y M eli ine, North Carolina ::1111 " lIlil l/ "" li l l y, 1\l rl l'I)'. I1 , N(I ,'lil l " 1" 01111 11

\ ' 1 111 ' 114 I ' \ I tr W ' 111 114111' 1 II ',1\ 1 II M Wvl i\ 1 I 'I ' !\ I ' III 'I(

I II I I~ II II ' t JlI~1 1 1I (J ' . ~ II, I I '1111 1

272 MATHEWS

Figure 1. A piece of white tape placed in a highly visible location is used to remind the surgeon to remove the circumanal purse-string suture and rectal sponges at completion of the procedure.

remove the suture at the end of the procedure. Preoperative enemas should be avoided, as this increases the likelihood of contamination by liquid feces .

3. The perineum, ventral surface of the tail base, and perivulvar region are liberally clipped and then scrubbed with povidone-iodine (Fig. 2). . .

4. The dog is placed with its pelvic limbs hanging over the edge of the surgical table. The edge of the table is well padded to prevent ischemic or neurologic injury (Fig. 3).

5. The dog's thorax is placed in a padded trough or held in place with tape to prevent rotation. The table is tilted 30° (head down) and then elevated so that the vulva is at a comfortable working height. Because of the head-down position, these animals are at increased risk of regurgitation and subsequent aspiration . The stomach must be empty (a minimum of 12 hours off feed). A cuffed endotracheal tube should be used to prevent asp iration. Finally, the pharynx should be examined a t the end of th pr -dure and suctioned if needed before r Coy ry from nn slh 'sia.

6. The tail is taped forw ard ov ' r the lon.;n l micllin ' .

EPISIOTOMY (CAUDAL APPROACII)

1111 1' 1111 "III II ii' Il lIlI I 1'1 11' 11 11, 11 II' 111 11 1 , 111 1 l ' I'lidll l lll l! \, II It 'IJIIi II.d III

11!J illl\" I' I " HI IIII ' ,01 II" . \" I lillll 111111 \ ,1) ', 1111 1111111 ' 1/ ' \ 1111111 1111 I'

SURGERY OF THE CANINE VAGINA AND VULVA 273

Figure 2. Following placement of the purse-string suture, the perineum and perivulvar skin Is liberally clipped and scrubbed in preparation for surgery. Note the infantile vulva.

1llIlIlh 'l 11 111 1111 1111111' 1II11 I 1111'"11 IIllWlll oi IIVill 11111 til II 1111 1111111111 11 111 I II Il il ll l 11110111 I IIII III IIi," I, 1111111 1, 111101 I" willi I If II IlIlIiI fI 111111111 I IlIh'lllIl 111 11 11 lillil l I II 111 1 III Illilvillil 11,,1111111111

274 MATHEWS

made in a dorsoventral direction ventral to the anal sphincter through the dorsal vestibular mucosa.8, 28

Placing a flat instrument such as a scalpel handle in the vestibule while the incision is made helps to stabilize the tissues (Fig. 4). If the surgeon plans to resect any ventral vaginal tissues, the urethra must be catheterized to prevent iatrogenic urethral damage. Hemorrhage is controlled with electrocautery and ligation of larger vessels such as the dorsal labial branches of the perineal artery. As is the case with any perineal surgery, hemorrhage can be profuse. Exposure is improved with Gelpi perineal retractors or by placing stay sutures on either side of the incision. Vaginal surgery in general is greatly facilitated by using an assistant, who can provide retraction, cauterize, and handle a suction tip while the surgeon proceeds unencumbered. An instrument holster decreases the risk of dropping the electrocautery and suction tips. A sterile 60-mL syringe case with umbilical tape threaded through a hole near the mouth makes an excellent holster. The umbilical tape is clamped to the surgical drape lateral to the field. Hoses and cords are draped over the dorsal aspect of the patient to keep them sterile and out of the way. Closure of the episiotomy is performed in three to four layers depending on the size of the dog (Fig. 5) . Mucosal apposition is achieved with either simple interrupted or continuous 3-0 to 4-0 absorbable su-


Figure 5; The episiotomy is continued into the lumen of the vestibule/vagina. The dorsal vaginal mucosa (arrow) is closed first. A three- to four-layer closure is recommended .

tures. In smaller dogs, the subcutaneous closure is combined with the mucosal closure in the same suture pattern. Interrupted nylon skin utures are then placed. To prevent postoperative licking and premature

suture removal, an Elizabethan collar is placed. As previously mentioned, postoperative pain relief can be greatly enhanced with a fentanyl patch or epidural anesthesia before recovery.

VENTRAL APPROACH

A v ntral approach to the canine vagina is required less frequently. Il may b n cary, and is sometimes combined with an episiotomy, for lot<l l vl.lg in' tomy (e .. , vagin.al neoplasia and strictures that are not 11111 'nab l ' to 1'1'1 ' allda l app roC1 h). Th ventral approach has also been 11 ,' t'd 10 I l'rf()f"n l colOl l' y and cyS I()~ cxy in addi.tion to ovariohysterec-1(11)) il) .l ('; 1, I ' pf vi. 'vv l'o ll hVI'Ili.ll ion 1l ,,,'oci8tccl wi th vaginal prolapse.19

'I' ld,1 i, II 11, 11 1l 1. 11'd VI'I III ',1i Ilddl! II I' '11)1)[ 'I1IIl 'h l l'rfol'l1wtl jLls l' n'8 ni al to IIII' 1'1'1 1111. 11 111'1 II ' 1'1 11 1. '1'111 ' 1ili lilil 'V 11111"111 '1' iH I'vll'Il II I'wd 1)[1 1 of 1'11<'

111'1111111 ii i 111 '11 lill ' ,11 '1'1'/11 1111 111 ' VII)" 1111 ( ', 111 ' III 111'1'11 ti l " V()l tll 'XI'I'HI Iv(' d il/ III I I) II I ii II I " 11111"11111 Iii 11)1' 111 '11111I 'llll ld II I \'1 11 ', 11 11 1 11111 11 11 '1, wiJ l'iI III I\, I I ' Iill III III 1I111 \' III <1111 111 1'111 11 1'111 111111111 1 I.d I' 11<1 1111' II I 1111'1 '111 111 '

276 MATHEWS

vagina and urethra, pelvic osteotomy may be performed.2 The ventral incision is extended caudally over the pelvic symphysis. The adductor muscles are freed at their origins with a periosteal elevator to expose the pubic and ischial rami (Fig. 6). Holes are drilled on either side of the four proposed osteotomies. Additional holes are created so that the musculature may be sutured to the pelvis at the completion of the procedure. The obturator nerves are identified and protected. An osteotomy is made in the pubic and ischial rami, thus freeing up the floor of the pelvis. The osteotomies are created with a Gigli wire, rotating burr, or sagittal saw. The origin of the left internal obturator muscle is cleared from this pelvic segment with an elevator. The surgeon can then swing the pelvic floor out of the way to expose the entire pelvic canal. After vaginectomy, the pelvic floor is wired back into position (18- to 20-gauge

Figure 6. Ventral approach to the female urogenital system vi p Ivle t t my. (D 9 I In dorsal recumbency.) Ventral musculature I I vat d I I'omlly (1\); 11 t1 1< , Ir pl'oc ll'lll( LI III the pubis and ischium and will act a an h r p In It; 10 1' Olll' 11[J1l Will i II HI t 111111 111 (II), I hI pelvic symphysi I I votod (Inti rool(O(I 1111 1 II,IIV (G) II I I II IIIIIIV" lI)( jlll 111 /1 pi 111/ 1 iI<llvh, canal. (From All n , W, , IOWI II WA' VIIIIII II 11j1i11 11 11l1J III 111 11 !,,,lvl, IHIII II iii 11 \1 1 /111 11 !I II do J. VI)I lli n ;' () : II II 1: ' 1, 111 11 willi 11111 111 11111


stainless-steel cerclage wire) using the predrilled holes. Adductor muscle fascia from either side is sutured to its contralateral partner. The rest of the closure is routine. Exercise restriction for a minimum of 4 months is recommended to promote healing at the osteotomy sites.

SPECIFIC PROCEDURES

Vulvoplasty (Episioplasty)

Recurrent urinary tract infection (UTI) has been associated with perivulvar dermatitis. Overweight bitches with infantile vulvae may develop perivulvar skin folds that are prone to urine trapping and subsequent dermatitis.24 Concurrent abnormalities such as vaginal stricture should be ruled out before surgery. Preparation is identical to that for episiotomy. The amount of skin to be removed should be estimated and outlined with a sterile marker before excision. Two inverted Ushaped incisions are made lateral and dorsal to the vulva. A horseshoeshaped section of skin is removed, often along with extensive amounts of subcutaneous fat (Fig. 7). If complete elimination of skin folds is not achieved when the skin edges are apposed, more skin is trimmed away. A double layer of interrupted sutures is then placed for closure (absorbable sutures subcutaneously and nylon sutures in the skin).

Closure of an Anovulvar Cleft

This is a rare congenital anomaly in which a trough exists between the ventral anus and the dorsal vulva. The defect results in fecal contamination of the vestibule and is corrected by creating either an H-shaped or inverted V-shaped incision between the anus and vulva. The dorsal vulva or vestibule is then closed in multiple layers similar to the closure of an episiotomy. This completely separates the anus and vulva.6, 27

Rectovaginal Fistula Closure

omll1LU'lications between the rectum and vagina are rare; when p r'~ nt, they a r usually associated with atresia anP, 7, 17, 20 Puppies with 1\ re tov gin al fi stul a pass feces from the vaginal orifice, The location i\ l)d Hi:;: ' of th ' fistuln ar dctcnn ined by vaginography or a barium 1'1)(' 11) 11 . ' 0 1' 1'('('1 ion on(oJ it'! tH of 1m ) I i ng an incision between the anus (if IllI'l 'I ' j !lilt') ilnd /11(' don'Hd v tll va l' ('ommi SflUI' '. Blunt di ection is , ' II'I 'II'd otll III Ill(' Ivvl'l pi IIH' 11 11 1,lil . ( 'r ""l'I('ri :;:nlion of fhe fis tLil a may ,.id 1\ il t Id, 'ltl lli, ',Jfllll\, ')'il, ' l it Iitl il 111,l lil"I' li l '"lIl 'd Ill' l'I 'I'('I ' It ' t! , rllll ()w('ci Ily 1'1'1'11111 11 '11 1'1111111111111' .I111 'll ti wil li II I 11\1' v , I),, 1111I IllId IIII' "1111 ' Ii 1'I'I' fIHIl .

II Itll l 'l li 1111 1'1 II I/I I I /111 '11' 111 / 11 11 / / 11 ' / 111 Ii .d II 11\111 II )" It II 1111 / 1,,11 IIVI ' I'

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278 MATHEWS

Figure 7. A, Typical appearance of a hooded vulva. B nd C, P rlvulvar I<ln nnel f t I excised dorsally and laterally until elimin ti n of p I'lv~ilvn r lll<ln f I II III n 1110v d,


tion is continued around the distal (blind) end of the rectum, which is grasped and pulled caudally. The rectum is then incised and sutured to the skin incision (anal orifice).

Resection of Edematous Vaginal Mucosa (Vaginal Edema, Type 1-11 Vaginal Prolapse), or Pedunculated Vaginal Masses

After episiotomy and urethral catheterization, the mass or edematous or redundant mucosa is isolated, and a fusiform incision is made around its base (Figs. 8 and 9).28 The base of this edematous tissue originates from the floor of the vagina just cranial to the urethral papilla. Partial-thickness incisions and single-layer closure are performed if resecting edematous vaginal mucosa. Electrocautery is quite useful when performing this procedure (see Fig. 9C). The urethral orifice is easily visualized for catheterization by elevating the protruding tissue. Pedun-

c

I I lure II. I\, I IIlIIn IIIl" V 1111 11 II II II( plllllll llill ( Iypo II vnnlnol prolnpfl ) Ihrougl, the Vil lvil l 11111 11 /11\1111 C, II llilil II Y 111111 11111" I j pllllllll i wl ll ll il 1110 '" 01'111'11 VI Ill! II 10 IiH It11 10 Pi/ IVIII II I il l II 1111111 11 1111 "1 11 III Il llI 11I 'l lilf ll l I' lIplllll 111111111 tlX1l1 I"" (lJ) (/ fIJI/I Wyllll, I'M, (I I II II I'N V I Jlrll , VI IIIIIlI lIlI llIl vi llvll 111' 1111111'1 11(111 1) JIIXll ll HII II I ' llI dl llllllllll l l ll'l JIII V, " d " l 'ldh,d rl lldl lll , Will 111 1111 111/1, 1111 11, " " 1 11111 Il lf'l wilIi IH'1I1I1 111 11 )

280 MATHEWS

Figure 9. A, Edematous vaginal tissue protrudes (Type II vaginal prolapse) through the vulvar cleft. A urinary catheter (c) is placed within the urethra ventral to the mass (8) to prevent iatrogenic trauma to the urethral papilla during excision (C). Electrocautery facilitates the excision of the highly vascular vaginal tissues. (Courtesy of E.A. Stone, DVM, MS, North Carolina State University, College of Veterinary Medicine, Raleigh, NC.)

culated vaginal tumors are remov I with full - I'hi el n'SN in iHiolls fo llowed by a double-lay rlosurc. M0f4 1 b 'ni gn (IIII1\)I'S lH' vn, il i!i'('('HHi ble with th aid f nn LI i,' in lom l 10 iIi,! roVl ' 1''< 1'1 1/ 1111"[ ' , 1\1'(lll d Ild ll('"

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(kl ('ndill )', OIl Il lI'i l I II" III '11 '11', II

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in young intact bitches during proestrus or estrus.28 Large and brachycephalic breeds are frequently reported with this condition. It may also occur late in pregnancy or during parturition. Edema in the submucosal tissues at the floor of the vagina just cranial to the urethral papilla results in elevation and stretching of the overlying mucosa. In mild cases, the tissue does not protrude through the vulvar cleft, and treatment is usually not required. This is referred to as type I vaginal prolapse by some authors.13,23 Vaginal edema regresses at the end of estrus, however, and the recurrence rate is high. When the pear-shaped mass of tissue protrudes through the vulvar cleft (type II vaginal prolapse; see Figs. 8 and 9), it is prone to trauma and self-mutilation. Dysuria may also be reported. Conservative management consists of placing an Elizabethan collar on the dog and keeping the tissues lubricated until they regress after estrus. Hypertonic solutions can also be applied (e.g., 50% dextrose) in an attempt to shrink the tissues to some degree. Hormonal therapy may also be attempted.13, 28 Ovariohysterectomy is curative and should be considered to prevent recurrence. If the dog is intended for breeding or if the tissues are traumatized, surgical excision is recommended. In severe cases, there is circumferential involvement of the vaginal mucosa with protrusion of a ring of tissue through the vulvar cleft. This is r 'ferred to as vaginal prolapse or type III vaginal prolapse (Fig. 10).13, '1, 28 Although the vaginal lumen lies dorsal to the mass of tissue in dogs with less severe forms of vaginal edema (type I-II vaginal prolapse), the vaginal lumen of dogs with type III vaginal prolapse lies within the t' 'nter of the mass of tissue. Resection of this edematous ring of tissue lhus requires a different technique.

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282 MATHEWS

Thankfully, tumors of the vulva or vagina are uncommon (2%-3% of canine neoplasms), and most are benign and pedunculated.S, 26 Bitches with vulvovaginal neoplasia frequently are presented with a history of vulvar discharge or because the owner noticed the mass protruding between the labia. Other clinical signs such as dysuria, stranguria, pollakiuria, tenesmus, and vaginal bleeding occur less frequently.

Before tumor excision, either incisional or needle (Tru-Cut; Travenol Laboratories, Deerfield, IL) biopsy should be strongly considered. A complete workup should be completed, including urinalysis (with culturing if suggestive of a UTI), digital rectal and vaginal examination, vaginoscopy, abdominal palpation, and palpation of regional lymph nodes. Thoracic and abdominal radiography and abdominal ultrasonography should be considered to look for evidence of metastases. Exfoliative cytology may aid in the diagnosis of transitional cell carcinomas or transmissible venereal tumors. In addition, vaginourethrography may aid in preoperative planning. 1, 11, 12 Pneumovaginographyl has been described, but positive-contrast vaginography is performed more commonly.lO, 12 This technique is also useful when evaluati'ng incontinent dogs with potential ureteral ectopia, vaginal strictures, or pelvic bladder. General anesthesia is required. A Foley catheter filled with iodinated water-soluble contrast media is inserted into the vestibule, and its bulb is inflated. Contrast media is infused while the vulvar labia are held shut with sponge forceps or Allis tissue forceps. A total volume of 1.0 to 1.5 mL/kg is typically used.lO, 12 This process is aided by the use of fluoroscopy if available.

Brodey and Rosze15 retrospectively evaluated 96 uterine, vaginal, and vulvar tumors in dogs. Thacher and Bradley26 evaluated 99 vaginal and vulvar tumors. The mean age of the dogs at the time of diagnosis was 10.8 years for both reports. Results from these studies showed that most tumors in the female canine reproductive tract (ovarian and mammary neoplasia excluded) are benign (73%-84%). Leiomyomas occur most frequently and originate from smooth muscle layers within the wall of the vagina or vestibule.s, 14,26 Multiple leiomyomas may occur in the same . animaP, 14, 26 Leiomyomas may develop intraluminally, in which case, they are usually pedunculated and originate from the wall of the vestibule.s Extraluminal leiomyomas are much less common, usually originate from the dorsal vestibule, and present as a firm perineal swelling.s Leiomyomas seem to be endocrine dependent. 14 Dogs with vaginal or uterine leiomyomas may have concurrent ovarian follicular cysts, estrogen-secreting tumors, endometrial hyp rp lasia, o r mammary hyperplasia or neoplasia.14 Bi tches thGll" GI l" spay 'd 'ti dy in li fe 10 not seem to develop genital I iOI11 YOI11 C1K .II Ovol"iohys lvrl'l'i OIll 111:1y result in tum.or sbri nkag,.I'1 Pibrol11Zl S, p()1 I H, Hild lipnlll ll , 11 \[1' :lI lm occur in thi a l" 1:'1. Su rgic: 1I l' (' i, iO I\ in IIHtl dll y' 'liI'lI llvl' If' 111(' 11 11 1, H I b n ign. Mnli gn,JIlI Vlil vl)Vd)', li lld 11I 111lI l'/ (I I"" 1'1"11 ) 11, 11'1' 111 10 IWI' II 1'\'

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amount to approximately 10% of the tumors in this region, should also be considered as a differential diagnosis.s,26 TVTs may be removed surgically, but are highly responsive to radio- and chemotherapy.21,2s Spontaneous remission of TVTs may also occur. Transitional cell carcinoma originating from either the bladder or urethra results in typical urinary tract signs (e.g., stranguria, pollakiuria) and may progress distally to form a palpable vaginal mass. I8

Partial Vaginectomy for Necrotic or Traumatized Vaginal Prolapse

In cases of long-standing 3600 (type III) vaginal prolapse, damage to the vagina may be too severe to allow more conservative management (i.e., cleansing with hypertonic solutions, replacement and temporary suture closure of the dorsal vulvar commissure) (see Fig. 10).13,28 Preparation for this procedure is similar to that for episiotomy. As is the case with any procedure requiring vaginal resection, the urethra should be catheterized first. The prolapsed vaginal tissue needs to be elevated to visualize the urethral papilla. An episiotomy may aid this process. Partial vaginectomy as described here is analogous to the technique used for rectal resection after rectal prolapse. The procedure involves the removal of a "donut" or collar of traumatized tissue. The vaginal lumen is in the center of this tissue. Placing a sterile lubricated syringe case into the vaginal lumen helps to orient the surgeon and allows the surgeon to apply counterpressure during excision. The initial mucosal incision is made dorsally proximal to any damaged mucosa. The scalpel blade passes through the muscular and outer connective tissue layers of the everted vagina. The blade then passes through the layers of the noneverted portion of the vagina in reverse order, finally coming to rest on the intraluminal syringe case. If a circumferential incision is made to 1'l'1110Ve the damaged tissue, the cranial vagina retracts into the pelvic I'[l nat where it is difficult to retrieve. For this reason, the incision is 1l18de in a staged manner. Starting dorsally, no more than one fourth of I ht' ircumference is incised . A two-layer closure of this section is performe I. with absorbable suture material. This process is repeated until I hr 'n ti re ring has been resected. The suture line is then allowed to 1'('\ nl \ into the pelvic canal.

Correction of Vaginal Septa, Bands, Strictures, and t no os

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MA'I'III (WS

A

Figure 11. Some of the more common forms of congenital vaginal anomalies include vaginal bands (A), vaginal septa (B), annular strictures just cranial to the urethral papilla (C), and vaginal hypoplasia/stenosis just cranial to the urethral papilla (0). (From Wykes PM, Olson PN: Vagina, vestibule and vulva. In Slatter D (ed): Textbook of Small Animal Surgery, ed 2. Philadelphia, WB Saunders, 1993, pp 1308-1316; with permission.)

or dystociaY· 16. 22, 28 Urinary incontinence may also be reported and may be true incontinence as a result of coexisting congenital abnormalities such as ureteral ectopia or pelvic bladder. On further questioning, it may become clear that the dog is not truly incontinent but dribbles urine when lying down, presumably as a result of passive release of a pool of urine that has collected cranial to a strictureY·28 It is this pooling of urine and vaginal secretions cranial to the stricture that thEwretically predisposes these animals to UTI. A complete workup should include a digital vaginal examination, vaginoscopy, and vaginourethrocystography (see section on diagnostics for vaginal masses). Other congenital anomalies (e.g., ureteral ectopia, pelvic bladder) should be ruled out. A urethral pressure profile should be considered.

Vaginal septa are the result of incomplete medial fusion of the Mullerian ducts. They run parallel to the long access of the vagina and may extend from the vestibulovaginal junction to the cervix. Septa may be incomplete or may form a blind-ended pouch (double vagina).22. 28 Episiotomy is generally required to gain adequate access for sep tal resection. The septum is excised from the floor and roof of the vagin a. The vaginal mucosa is then sutured to prevent adh ion or slri tur ' formation. Long-term follow-up da ta on dogs [l rh.: r S(' I 1'<-1 1 C ision , rl' lacking.

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examination, vaginoscopy, or contrast radiography may reveal a circumferential narrow fibrous ring of tissue in this region (Fig, 12), Vertical bands are also caused by incomplete perforation of the hymen but are easier to treat (Fig. 13). Resection of single vertical bands may be accomplished with the aid of a vaginal speculum. Under general anesthesia, the band is stabilized and retracted caudally with a spay hook or long forceps. The band is then transected with Metzenbaum scissors. If the band cannot be adequately visualized, an episiotomy is required. Further examination of the vagina cranial to the band is then performed before recovery from anesthesia. Vaginal hypoplasia results in a broader area of narrowing than that caused by an imperforate hymen and is generally referred to as vaginal or vestibulovaginal stenosis.n, 28

Simple bougienage of vaginal strictures or stenoses has met with little success as the tissue healsY· 16 Dilatation of a simple stricture or persistent hymen is easily performed at the time of diagnosis and results in success in some cases. Dorsal incision of strictures or stenoses via an episiotomy followed by a T-shaped closure (vaginoplasty) to increase the vaginal diameter has also met with generally unfavorable results.n, 16

Good results have been reported for a few cases with complete ring resection. This technique involves episiotomy followed by urethral catheterization and 3600 dissection of the stricture or stenosis. Resection of a vaginal stenosis is technically more difficult than resection of a stricture or persistent hymen because of the amount of tissue that must be I' 'moved. Two circumferential incisions are made, one cranial to and one

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1'16 M i\'J'IIIiWS

Figure 13. A vertical vaginal band (within the circle) as viewed through a vaginal speculum. (Courtesy of E.A. Stone, DVM, MS, North Carolina State University, College of Veterinary Medicine, Raleigh , NC.)

caudal to the stricture or stenosis. Resection of the submucosal fibrous ring of a persistent hymen does not require a full-thickness i~cisior:' and the mucosa is easily sutured so that none of the deeper vagmal tIssues are exposed to the lumen. Full-thickness excision of vaginal stenoses is required. Catheterization and protection of the urethra are of t~e ~tmost importance during this technically demanding procedure: LIgatIon of vessels on the external surface of the vagina may be necessary. Once the ring of tissue has been resected, end-to-end anastomosis of the vaginal segments is performed (Fig. 14). Vaginectomy is the final option ~or correction of problematic vaginal stenoses in bitches that are not mtended for breeding. Results with this technique seem to be favorable . Complete vaginectomy with removal of the stenosis can be performed via a caudal approach in spayed bitches or combined with a standard ventral midline ovariohysterectomy.16 Partial vaginectomy v ia a a Llda I ventral midline approach may also be performed, II Th vagina is li gat d and resected as close to th stenosis a possibl' I:(J jirnini :-; h I'he poss ibi lity of urine pooling. O f '10 clogs Ir 'ai'ccl w ilh Ihi !> k chniqlll', 7 lind 'ood results.·11

Complete Vonln ctomy

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Figure 14. Circumferential excision of a vaginal stenosis has been completed. Urethral catheter (c), and circumferential interrupted mucosal sutures at the level of excIsion (arrow· heads).

The best exposure is gained via the ventral pelvic osteotomy previou~ly discussed. After careful dissection, clamps are placed across the vagma just cranial to the urethrovaginal connection, the vaginal vessels are ligated, and the vagina is transected. A Parker-~err ove~sew or other inverting suture pattern is used to close the .v~gma. VaglI~ectomy can olso be performed via the caudal approach (epISIOtomy reqUlred), !" fullthickness circumferential incision is made caudal to the stenOSIS and vranial to the catheterized urethral papilla. The vaginal vessels are IiI' a ted, and cranial dissection continues along the. outer surface of the l'I'o nial vagina and cervix ';lntil the uterine. stu~p IS ~ee and resectable, 'I'b caudal vaginal lumen IS then closed WIth slffipl~ ~terrup.ted absorbdb l . sutures cranial to the urethral papilla. The epISIOtomy IS closed as I'rav iOLl ly discussed. In sexually intact female dogs, a combination of lilt' lwo (v ntral midline and caudal episiotomy) approaches may be 1I1'l('d flO tha t i t11ultaneous ovariohysterectomy may be performed.

Vulvovaglnectomy with Perineal Urethrostomy

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1'1'1 ,111 ,\ I II 11\1 ' ,I,) )" II II I' II ,tll illld"I , IlV,\ I'lllh YH II'I'I 'I'III I)) In PI ' r\tlrt)I( ' ti \ ,,01 I.llIti ,"d I'I' III" ,t! 1'1 '1'"1011 II '1'1" , ,I, I)', III IIii'll 1'1.11 " ',1 III 1, ' 111 ,11 11'1 111111 '1 ' 111 \ III 1II I' I 'I\'Idlllll I," 11 11'1, 111 11.11 ' '1 '1111 111 1,1, ' II II' d ll "', Ih 'll II '

2/lH MA'J'I IEW '

quired for this procedure is somewhat analogous to that performed for a rectal pull-through (Fig. 15). A fusiform incision is made around the labia. Dissection continues along the external surface of the vagina. The urethra is catheterized and dissected free, clamped, and transected from the vagina. In spayed bitches, the cervix and uterine stump are also removed. Once the vulvovagina has been removed, the defect is closed. The urethra is incorporated in the closure to create a perineal urethrostomy. Survival times in these three dogs were 9 weeks (transitional cell carcinoma, died of unspecified causes, no necropsy), 7 months (fibroleiomyoma, euthanatized because of metastatic mammary carcinoma, no local tumor regrowth at necropsy), and 10 months (anaplastic spindle cell sarcoma, euthanatized because of tumor regrowth first noted at 7 months after surgery). Postoperative complications were minimal and incl~ded (one examp~e of each) mild urine scalding, transient stranguria, parhal stomal necrosIs, UTI, and mild stress incontinence. Because large numbers of dogs have not been evaluated with this technique, owners

B

stay sutures on urethra

ligated branches of vaginal a. & v.

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should be warned of all possible complications associated with aggressive surgery in this area.

SUMMARY

Accurate diagnosis of canine vaginal abnormalities often requires general anesthesia, vaginoscopy, and contrast radiography. Abdominal ultrasonography, thoracic radiography, computed tomography, and histopathology may also be advised for the workup of mass lesions before surgery. Many procedures such as episioplasty and resection of pedunculated vaginal masses or edematous tissue are easily performed with proper planning and equipment (e.g., electrocautery). Consideration should be given to referring more complicated procedures such as reseclion of large vaginal masses or vaginal stenoses to a board-certified Hurgeon. Finally, preoperative placement of a fentanyl patch and preor postoperative epidural analgesia are highly recommended for any vulvovaginal surgical procedure.

References

I , Adams WM, Biery DN, Millar NC: Pneumovaginography in the dog. A case report. J Am Vet Radiol Soc 19:80- 82, 1978

", A llen SW, Crowell WA: Ventral approach to the pelvic canal in the female dog, Vet UL'g 20:118- 121, 1991

I, Amand WB: Nonneurogenic disorders of the anus and rectum. Vet Clin North Am mall Anim Pract 4:535-550, 1974

'I. Uilbrey SA, Withrow SJ, Klein MK, et al: Vulvovaginectomy and perineal urethrostomy fo r neoplasms of the vulva and vagina. Vet Surg 18:450-453, 1989

r" Brodey RS, Roszel JF: Neoplasms of the canine uterus, vagina, and vulva: A clinicopa thologic survey, 90 cases. JAVMA 151:1294-1307, 1967

II. Burke TJ, Smith CW: Vulvo-vaginal cleft in a dog, J Am Anim Hosp Assoc 11:774-777, 1975

'I, ( :1' ' in r TP: Surgery of the rectum and anus. Vet Clin North Am Small Anim Pract :'167- 180, 1972

K, Ilnr Ii EM: S lected surgeries of the male and female reproductive tracts, Vet Clin NOI'th Am mall Anim Pract 14:109-122, 1984

" Il l'l1drix PK, Raff MR, Robinson EP, et al: Epidural administration of bupivacaine, Ill orphin " or th ' ir combination for postoperative analgesia in dogs. JAVMA 209:598-W7, 1996

III 1111 11 1'1\: l'OHIli v'- onlros t vaginourethrography for diagnosis of lower urinary tract d IH\','H\' , 1/1 Kirk I{W (<' eI ): IIrr 'nl' V t ' rinary Therapy X- Small Animal Practice. 1'ldll1d" lph l,i , Wil S1l 11i111v1'H, 19K'!, I P 1142 1'145

II I lnll 1'1\, Sily ll' 1\: ( '()n)jt'nll il l vl'Hllbldn vngln.II ~ l ' n o~ i ~ in th' bit h. J Small Anim Pract 1" 1177'" 1'/11 1

I ' llidl 1'1\, (; 11 ,1111 ( ', 1"IIIi" I'1 " A ll "", III"ll itll l II I jloli ll vl' \'I II II",iHI V' \I\I 'HIIII'(' lh l'ng l'a phy 111' 11 d lllH l lllldl. "I d III 1111 ' " Iii Ii / il lll l"l 111 1111 '1'11, '1 '11,,'1 ' \1 ',,1'1 , 1'111"

1\ /,,1'11 11111 '1 ': 11 VI I)II II II II 'III I' II 'III ' 11/ I " I 'W ("d ) 1 11111 '111 VI, I,,, III I1 I Y '1'ItI '" '1 ly \ :: 111 11 11 11 11'1 11 1 I 'll" I 'I ' l 'hll llll " I/ " "" IVII ' II lIlll dl I ~ 111(\'1 I II ' I III ' I 1111,

II /11 111, I VI' I 1'11 111 '" '' 1'1 1'11 111111 N (, Ii ) I ',d/IIIIII)\ \' " I II " 1 11l1l1I '~ 1I1 \ 111 ,,,, ,,,, l ,tI I \ " I \ 'I" , I I 111')',11 \, 111/' l ill, I 'll I 'll/ \ ,"d

290 MATHEWS

15. Kyles AE, Papich M, Hardie EM: Disposition of transdermally administered fentanyl in dogs. Am J Vet Res 57:715-719, 1996

16. Kyles AE, Vaden S, Hardie EM, et al: Vestibulovaginal stenosis in dogs: 18 cases (1987-1995). JAVMA 209:1889-1893, 1996

17. Louw GI, Van Schouwenburg SJEM: The surgical repair of atresia ani in a Doberman bitch. J S Afr Vet Assoc 53:119-120, 1982

18. Magne ML, Hoopes PI, Kainer RA, et al: Urinary tract carcinomas involving the canine vagina and vestibule. J Am Anim Hosp Assoc 21:767-772, 1985

19. McNamara PS, Harvey HI, Dykes N: Chronic vaginocervical prolapse with visceral incarceration in the dog. J Am Anim Hosp Assoc 33:533-536, 1997

20. Rawlings CA, Capps WF, Jr: Rectovaginal fistula and imperforate anus in a dog. JAVMA 159:320-326,1971

21. Rogers KS, Walker MA, Dillon HB: Transmissible venereal tumor: A retrospective study of 29 cases. J Am Anim Hosp Assoc 34:463-470, 1998

22. Root MV, Johnston SD, Johnston GR: Vaginal septa in dogs: 15 cases (1983--1992). JAVMA 206:56--58, 1995

23. Schutte AP: Vaginal prolapse in the bitch. J S Afr Vet Med Assoc 38:197-203, 1967 24. Scott DW, Miller WH, Griffin CE: Muller and Kirk's Small Animal Dermatology, ed 5.

Philadelphia, WB Saunders, 1995, p 887 25. Singh I, Rana JS, Sood N, et al: Clinico-pathological studies on the effect of different

anti-neoplastic chemotherapy regimens on transmissible venereal tumours in dogs. Vet Res Commun 20:71-81,1996

26. Thacher C, Bradley RL: Vulvar and vaginal tumors in the dog: A retrospective study. JAVMA 183:690-692, 1983

27. Wilson CF, Clifford DH: Perineoplasty for anovaginal cleft in a dog. JAVMA 159:871-875,1971

28. Wykes PM, Olson PN: Vagina, vestibule and vulva. In Slatter D (ed): Textbook of Small Animal Surgery, ed 2. Philadelphia, WB Saunders, 1993, pp 1308-1316


Kyle G. Mathews, DVM, MS North Carolina State University College of Veterinary Medicine

4700 Hillsborough Street Raleigh, NC 27606

;

j

CLINICAL THERIOGENOLOGY 0195-5616/ 01 $15.00 + .00

TRANSCERVICAL INSEMINATION TECHNIQUES IN THE BITCH

Marion S. Wilson, BVMS, MVSc, MRCVS

The technology to freeze and inseminate frozen semen has been ilround for over 30 years, but it is only relatively recently that there has heen an upsurge in its use as breeders take advantage of the benefits it offers to their breeding programs. This increased use is mainly because of the improved conception rates now being achieved as a result of Il ctermining the critical factors for success. Defining the optimum time 1'01' insemination and developing methods for determining this critical I i me have had a significant impact on improving the success rate; also Important has been the recognition that thawed semen should be deposItl'd by intrauterine means rather than vaginally. 1, 2, 4, 10 This overcomes I he effect that processing has on the ability of the sperm to migrate Ihrough the cervix and reduces the sperm dose perceived as required 11\ ' 1' bitch.

The options to achieve intrauterine semen deposition are by surgical I II' transcervical insemination (TCI). In many parts of the world, the 'tiI rg ical option is the method of choice because it is easy to perform and II ,IS no major learning period. Surgical insemination has some drawI'dei " in.eluding the risk associated with general anesthesia and surgery oIl ld the fac t tha t only a single insemination is realistic (and ethically 111 '('( ' 1 table). Many owners and veterinarians prefer a nonsurgical trans-1 l' l'v ica l opti.on; in some countries, it is considered ethically unacceptable II I Iwrform intra uterine insemination surgically. Previous reports have Ill tli( 'i ll'cci th , t T T is not possible or that it is feasible only in the lilli' 11H'li zc I bil: 'h. Mol" recn tly, techniques that contradict these opin-

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292 WILSON

ions have been developed.ll The problems faced in any attempt to catheterize the canine cervix relate to its relative inaccessibility.

In addition to frozen semen insemination, the ability to catheterize the cervix in the bitch provides clinicians with the opportunity to access the intrauterine environment without the need for surgery. This means that an extended range of procedures can be performed and that they can be done routinely and repeatedly if necessary, without undue stress to the bitch.

ANATOMY OF THE CANINE REPRODUCTIVE TRACT

To catheterize the cervix, it is essential to be familiar with the anatomy of the reproductive tract of the bitch and the features preventing routine access using standard equipment.

Length of Vagina

The vagina of the bitch is comparatively longer than that of most species; the total length from cervix to vulva, including the vestibule, has been reported to be 10 to 14 cm in an ll-kg bitchY

The practical significance of this distance to the cervix means that relatively long equipment is required; in large breeds such as the Saint Bernard and Newfoundland, this length can be up to 29 cm.

Paracervix and Dorsal Median Fold

The cranial vagina, described as the paracervix/ is dominated by a well-defined fold, the dorsal median fold (DMF) (Figs. 1 and 2). The DMF extends caudally from the vaginal portion of the cervix, which

cranial

o

dorsal

ventra l

vaginal lumen

Figure 1. The anatomy 01' 111 11 p/ll /ltll ll VI I I ll IWlll l ll ll i dill 11 1111111 11111 1 rilid (I IMI ) 1111 11111111 111 1 caudAlly In tl1 fllUHl ll llill lt lll lli (I I), 11 111 Vl li llt ll ll i ll illllill " I II IIII IIIvl III IIIIIVIIlIl II IlIiIll IlI" ( ,) wi ll i Vllll l1 /llll li llll ll ll lVlllll l 'l I I) 111111111" 111 1111- (I )

TRANSCERVICAL INSEMINATION TECHNIQUES IN THE BITCH 293

Figure 2. Ventrolateral view of the paracervix. This anestrous reproductive tract illustrates the position of the dorsal median fold (arrow), cervical tubercle (C) and extemal cervical as (0). During estrus the dorsal median fold undergoes marked enlargement and the caudal tubercle becomes more pronounced.

l'xists as a distinct tubercle, and then ends in a smaller caudal tubercle. When viewed through a speculum, the caudal tubercle and narrow crescentic vaginal lumen have been described as giving the misleading nppearance of the vaginal portion of the cervix and external uterine ostium. When insemination catheters are introduced into this area, there is often some resistance and then a distinct "give," which may explain why some clinicians believe they do intrauterine inseminations routinely wh n, in fact, they are only inseminating into the paracervical area; the I rue cervix is to be found approximately 2.5 cm cranial to this pseudocervix. Cranially, the paracervix is limited by the fornix, a slit-like space CI'< nioventral to the vaginal cervix, which appears as a blind end when v il'wed through the endoscope.

The paracervix has particular relevance to cervical catheterization, 1 H.' <l LlSe reduction of the vaginal lumen by the DMF limits the size of t' lj uipment that can be passed through this area. The size of the lumen vdri' m.arkedly between bitches and is not directly related to the size 01 lh bi tch; it tends to be narrower in maiden bitches and in certain lin' ,ti s o r lin within breeds.

C nine Cervix

'l'lw 1'l' l'vi li ('. di agonnll n ross th Lit rova inal junction, with the , ,11 11 11, 11 II 1\' , '( ' I' i \ d ln,('\('d t'I'III )i()dors. lI y from the Vc gin, to th uterus ( 11(' 1111 '" I ) ( '( III III " l' lI'llIl y, II I" IIlI I' I'lln l O l'i ri {' l ' or I'Iw t\' I'Vi l ' lI I I'n nni fn s l il lI l(I /1 1 d l l 'I 'I '11 d,,, di y, w lll'i " 11I 1111 ' I ' I t'l' lidl lll'i ri ,'" Iii d in ','l t'd I II 11 11'

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II I I I! ' " " 111' 1 I" " I II 1' 11 , " I 1III I I II ' II I 1111 I1I I II 11'1 I" (II 1'1 ' I " I II I \ )

294 WILSON

Figure 3. The position of the external cervical os within many furrows on the cervical tubercle can be identified by the fluid issuing from it.

The angle of the canal means that passing a catheter through the cervical canal is not without its problems; the diameter of the canal also has a bearing on the technique. Recent work by Watts and Wright13 has revealed that the cervix is patent throughout the reproductive cycle of the bitch but that cannulation can be performed more readily at some stages of the cycle than at others. Experience in performing TCI has shown that the cervical canal varies in diameter, with maiden bitches presenting more often with a narrower lumen.

In summary, the length of the vagina, narrow paracervical area because of the DMF, position of the cervical os, and angle and diameter of the cervical canal present significant obstacles to the routine catheterization of the cervix with standard equipment.

TRANSCERVICAL INSEMINATION TECHNIQUES

There are currently two methods described that allow intrauterine insemination to be performed routinely in the bitch via the tran rvica 1 route; they employ different equipment and teclulique to ov r om tb obstacles presented.

"Norwegian" Method

ThiH IIll ' lhud Wil li I I/I I dl ' I ill,, 'd IIi' 111111 1',111 ' 1 1'1 , il l , II I I 1I,, 11I11 1!'1 1'

d, ' 1,I' l l ,, 'd 1111 II ii' 11111 1111 , -,1 111 ' 11I ' 1" 111i11111l1l1 1l 1 III " 111 1.1 \\111 ' Itl ll " 11I1"d


by Andersenl for the intrauterine insemination of frozen semen in the bitch. The equipment consists of a nylon sheath and metal catheter; these are produced in three sizes to suit bitches of different sizes (Fig. 4).

An assistant holds the bitch in the standing position on a table of convenient height. The sheath is passed along the dorsal wall of the vagina as far as it easily goes; it is often too wide to be introduced into the narrow paracervical area. The sheath is palpated through the abdominal wall, and the cervix is usually found 1 to 2 cm in front and slightly above the sheath. The cervix, which undergoes marked enlargement during proestrus, is fixed through the abdominal wall between the thumb and forefinger, and the metal catheter is introduced all the way through the sheath to the cervix. Manipulation of the cervix changes the angle of the cervical canal to a more horizontal position, and the tip of the catheter is brought into contact with the cervix while carefully searching for the os. Once this has been located, the catheter is advanced through the cervical canal; the ease with which this is achieved varies between bitches. There should be no resistance to the flow of the semen, and there is a distinct sound associated with the introduction of the final small amount of air in the catheter when the catheter is intrauterine. If the catheter position is incorrect, there is significant backflow between the sheath and catheter. Sedation is usually not required, as most bitches in estrus are happy to stand for this type of handling. With this method, it is important that the bitch should have an empty bladder ,l nd stomach to facilitate palpation?

"New Zealand" Endoscopic Method

This technique was developed as part of this author's degree progra m.16 The equipment used is a rigid cysto-urethroscope (Storz Ex-

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296 WILSON

tended Length Cysto-urethroscope, Coleta, CA), which consists of a telescope with a 30° oblique viewing angle, a sheath, a bridge, and a cold light source; the working length of the assembled endoscope is 29 cm (Fig. 5). A video camera can be attached to the endoscope, but this is not essential. When this technique is being used for insemination, an 8-French gauge urinary catheter is appropriate in most bitches for cervical catheterization, although a 6-French gauge is sometimes required in small or maiden bitches.

The bitch is restrained in a standing position on a specially designed platform on a hydraulic table; the platform provides a tie point to the dog's collar and a canvas band around the abdomen, which restricts sideways movement and discourages any attempt to sit. The use of the hydraulic table and chair ensures the optimum position of the bitch relative to the operator during the procedure and is helpful but not essential (Fig. 6).

The endoscope is introduced into the vagina and advanced through the vaginal folds by observing the direction of the vaginal lumen. In proestrus and early estrus, the rounded vaginal folds can make advancing the endoscope more difficult, because they tend to fill the lumen; as estrus p:r:ogresses, dehydration of the folds results in a more obvious route for advancement of theendoscope.9 The caudal tubercle of the DMF is usually a prominent landmark, and the lumen can become quite narrow in some bitches at this point, requiring manipulation of the endoscope to the widest space. This may result in the endoscope being

Figura 5. f:ncl (Jpln I fl ll lpl ll llI ll 1111 11111 \1 11 I Ivll )I" 111 111111 1111 1111111 1)1 11 1 111111 II I II II I/II 11 111 1111 111(1 G (1)1(1 (1\ ), : 1( )" I 1111111i 1l 1/1111 1\/i "v .111 111111111 11 ' li ll il l (I ), 11111111111 (I I), 111\l hll l (I ), 1\11111 1 ' 1I 111f11i 111 11 I" III IIUII Y • 11111101 111 (II)


Figure 6. Endoscopic transcervical insemination. The bitch is restrained on a specially designed stand; the abdominal band limits sideways movement and attempts to sit. The endoscope is advanced through the vaginal folds by observing the direction of the vaginal lumen. Catheterization of the cervical canal is achieved by manipulating the cervical tubercle, making use of the rigid endoscope and the catheter.

pushed to one side of the DMF rather than continuing ventrally under the DMF. The vaginal portion of the cervix appears as a distinct tubercle, hut as the cervical os faces caudoventrally or ventrally, it is usually not i II1mediately obvious. To locate the os, the scope must be advanced Iinder the cervical tubercle; the os is situated in the center of a rosette of furrows in most bitches, but in some, its position can only be identified hy observing serosanguineous fluid flowing from the cervix (see Fig. 3). 'I'h position of the os can seem to change through estrus with dehydraI iLm of the vaginal folds. The catheter is advanced into the cervical os hy manipulation of the endoscope and catheter. The rigidity of the (' ndoscope is used to move the cervical tubercle, line up the os, and vhe n e the angle of the canal. Once the tip of the catheter is introduced 1n l'0 the os, it is steadily advanced using a twirling movement to aid its pnssag through the cervical canal.

1"0 1' semen deposition, the catheter is passed in as far as it is able to ,;() without for ; it is important to observe the semen being inseminated III l' 11SLlr' that tb' ca theter is correctly placed and that backflow does 1101 occu r. In th ' ev 'nt of ""111. n ba kflow, the insemination is stopped filid I Ill' r ll l'h ' 1,('1' is r 'F osil:ioncd I' i th ' I' Furth r in or withdrawing slightly. ( \ )1\1 1\1, I Il ll'di n ('11 11 lw svC l1 Ih r(l( I)', holil both ho rns irnm.edi ately after IIII' Ill jl 'I'liu ll i. : IH ·rCU I'lll l'd II) ill)il rd,' .\ 11 iIISI' ln in il l'ill ll (Ii i)'" 7 ).

111\ 1'hl'l 111 1'11 11 '111 I'\ l li l l1 11111'. 1I IIIId 11 11', 1lt'/jd v i()1' HiJ()W " ('"II(' nl Inlc ri llll 'I ' I II 1111' 11 11'/ 11 11'1 111 ', III ·d 11 11 11111011 II I 'V I '" 11( 11'1) 1\1 11 111 1 111 111' 11 (1, '1'111 ,1I'y fo r 111/ 1'11\/iI,1I11111

1\ I 1)/ 11 11 1. Ii II " I ) I I " pi 'I" h' II " d II II I (II 111 \ 'Il l \\' 1 I I I , ' II II Ii II ( 'I ""

298 WILSON

Figure 7. Contrast media is evident throughout both uterine horns immediately following intrauterine deposition.

techniques, but when the procedure is used in the estrous bitch for insemination and general vaginoscopic assessment, air insufflation h~s been found to be unnecessary. During the early development of this technique, a deflecting mechanism was used to aid in the manipulation of the catheter, but with experience and acquisition of the current endoscope, the deflecting mechanism is no longer. used. Air ins~fflatior: can be achieved by connecting intravenous tubmg and a synnge WIth a three-way stopcock to one of the channels, whi~h is u~eful whe~ performing routine vaginoscopy in the nonestrous bItch to .Improve vIsualization of the vaginal lumen.

EVALUATION OF TRANSCERVICAL INSEMINATION TECHNIQUES

The Norwegian method has been described in several previous reports, so it is not discussed further here. I • 3. 6. 17 Only limited information exists in the literature on the endoscopic technique,13. 16. 17 and several questions warrant further explanation.

"Is It Easy to Learn Endoscopic Transcervical Insemination?"

The t c11ni Itl l' itl IIH'ol'l'lil '. lIl y I illlpl, ' hili lid, ' lilli" , Ihil ll' III "', .Il1d 1 rnelici' to PI 'I'(III'I ; II 1'1"1" II ' II 111 (11111 1)', 11 111111 ""tl l',I' 1)1 lilt , 1I 11, dllll\ V Itl


the reproductive tract, and time spent studying anatomic specimens is invaluable,

The attachment of a video camera to the endoscope allows direct training by an experienced operator, because it is possible to see what is happening, The trainee can visualize what he or she is trying to achieve, Most find the prospect of getting the catheter into the os a challenge that can be confidently achieved in a relatively short time; mastering the peculiarities of all breeds and sizes, however, takes longer.

"Is the Equipment Easy to Clean?"

The equipment can be readily cleaned and disinfected; early reports of long drawn-out procedures for endoscope cleaning are misleading. Consult the manufacturer for specific cleaning and disinfection recommendations.

"Can All Bitches Be Inseminated This Way?"

For the technique to be widely adopted, it is essential that it can be applied successfully to all (or at least most) bitches, and because the 'quipment is expensive, it is important that most bitches can be inseminated using the same endoscope. Looking at the vast array of breeds presented with regard to size and shape, this would seem unlikely but is, in fact, possible for the most part,

It is important to appreciate the limiting factors for each part of the procedure.

Reaching the Cervix

The maximum length of the vagina is a critical dimension; however, 110 bitch whose cervix is beyond the reach of the equipment described has so far been examined; thus, vaginal length is not a limiting factor. 1,0 r e breeds examined include the Great Dane, Saint Bernard, Mastiff, Il'ish Wolfhound, Newfoundland, Borzoi, Afghan, and Pyrenees MounIili n Dog. The external size and shape of a bitch does not accurately pI" Ii t the internal situation-some medium-sized bitches (i,e., German Sh 'I h I'd ) have vaginas as long as much larger bitches, Borzoi and Mghnl1 it'll '8 have urprisingly short vaginas.

'I'h (' one limiting fa to r id ntified i the amount of space in the 1' 11'.)1 '1'l'vi ; in n li mnll I Vl'c ' nt ogc' of bit h s, it is impossible to advance Ill(' (' IHl n, ('() liI' Ihmll )',h Ih i, ,11'( '. 1, 'I'hi , Ol't'lll'i-l in some maiden bitches of

11111 11 (I I' II H'dill lll :il '/,I'd 1II'I'I,d:l, .llll l itl :Itlllll ' 10 I I'(,(·d i-l (i ,I'" hihu Fl hu a). '1'111 '1'1' .11 '1' Wd I Itl tl 1'1'1'11 111 II )', lid /I Ill'o lli l' !!1 III :10111\ ' hlll'll(" ; how('vI' r, III Illlli 'l'l (1" 'tll,,,ll lv 11'/1/ II IIil l I'i,,), 11'1 '1' 1 III 11\1' l't'lV I, 111 '1'1 11 11 lilli ', I ,' III I (II I II I II ' I III 1111 " II 'I Ii II 1I1l! '11'1 Ill" II \ ' " II"" ,', I" II 1111' \ Ii II ' ,tI II I , 'I II I ' Ii" I 'I' Id,l v IllItll ' l 111111 111111 "" I 1111 111111.11111 1111 Itl\ 111I 'I,tl lI \ III 'I! ' II,, ·

300 WILSON

vaginal length is short. The standard endoscope described here has been used successfully in many small-sized and toy breeds (i.e., Pugs, Pekingese, Griffon Bruxellois, Cavalier King Charles Spaniel, and Miniature Dachshund) and is suitable for most bitches. Where toy breeds are a significant part of the reproduction workload, investment in a smaller scope may be necessary.

With the smallest toy breeds, restraint of the bitch while trying to manipulate a relatively long scope is a large part of the problem, and sedation may be the answer.

Identification of the Cervical Os and Cannulation of the Cervix Canal

Theoretically, once the endoscope has been passed through the paracervix, it should be possible to catheterize all bitches. The ability to identify the os, position a catheter at the os, and pass it through the cervical canal comes down to operator skill and experience and is not limited by the equipment or the bitch; sometimes, 'a smaller gauge catheter is necessary.

Most of the problems encountered result from not appreciating the anatomy of the tract and not having developed the knack of manipulation of the endoscope and catheter together. Another significant problem relates to vaginal discharges causing poor visibility; there are several tricks to deal with this. Not all bitches are easy to catheterize because of difficult anatomy, ongoing poor visibility, or fidgeting patients; occasionally, some dogs defy all attempts from even the most skilled operator.

"Is the Insemination Definitely Intrauterine?"

With visualization of the cervix, there can be no doubt that the catheter is intrauterine (Fig. 8). Continued viewing of the insemination process ensures that the semen is deposited in the uterus without backflow occurring; a video camera allows the client as well as the operator to observe the intrauterine deposition of the semen.

"Is the Technique Safe?"

The risk of trauma or infection is an important considera ti on, With the endoscopic technique, it is difficult to con civ the t the plas ti c urinary catheter could perforate th vagina l or [lI'c rin ' wull during ('s lrus unless a pathologic conditi on alread y l' is iS. Til l' P:IJ'il t'l' l'vil' llnrV,l CO lt! I be traumatized by the' Wi(' o f ill nppropl'i.III ' rll l'I'(', Ilt lw('v(' I'; i/ ,Id vdll l'ill !'. the endos o~ c ,lI , Vii U/! ViUII H di :i('(l lld llli 111 II\(' Iii it'll , lit( , 111'(1('(,11111 '(' sholiid 1)(' s lOl l l,1I Wllt 'li I ' .1 111111 11 111 111'11111 ' 1" '11 11 11111,11 tll ll ill )', 1111 .. ,11 11111 ,)II" tl ll': IIII I, Ihl < \d)',I' III I IV, III , Iii" 1I t1 111 1 .. 1 dlld II Jl111 ' 11111'1,,111 1, . II I


Figure 8, The catheter can clearly be seen in the cervical os and no backflow of semen is evident as the insemination is performed, confirming intrauterine insemination,

lrauma, and the bitch is likely to be sedated so does not react to inappropriate handling; extreme care should be taken in these situations.

It has been suggested that this technique could introduce infection 10 the uterine environment. During proestrus and estrus, bacteria are routinely isolated from the uterus and vagina without causing any ,lpparent problems, perhaps because of a greater resistance to infection I1t this timep,15 It is reasonable to assume that advancing a catheter from the vagina to the uterus at this time is not going to cause any problems. Nevertheless, care must be taken to ensure that no new infections are introduced as a result of inadequately cleaned equipment or from the environment through poor technique. During diestrus, the Hi I uation changes; under the influence of high progesterone levels, the II I 'ru may be particularly susceptible to trauma and infection, requiring IJw ia l ar and aseptic technique at this stage.13, 15

"What Results Can Be Expected Using This T chnlque?"

Thi s Iv(' illliqll l' lli'llvitil 's illll'll llU ' ril\l' ti c'pos ition of sem ·n, which is II 111111' '' 1'1111 11 'lI iI,('11 :11' 11\1 '11 it ,(' I II 1()1 1l)', , 1': '11,,111 illlp()rl.lll1 i'l l lh (' SLI SSIitl II PI' Iii 11 1l'/,1'1i 111'1111 '11 .11 '1< IIii'I lilill )', I tl 1l lliI' lilill.llillll , HI'I))!,11 \l11 ;1Iil I

dll ll hll l,11 1I' II IIII y 111111 111'111'11 '1'1 '1 III, , ' dll \, 11 11 11' 1' Idl' IIIII 'I'ill" ill llt' lnill ,1 1111 11 1111 ,111 11" II 111 11 \ Ii II I I' 1111 II ,til 11 11 "1 Idl lil l <I II' I,d I'l l illl lllIl' 1I1111i ,

302 WILSON

The use of TCI does mean that the bitch is likely to be less stressed by the insemination procedure and permits repeat inseminations.

Results from a trial comparing the Norwegian and New Zealand ndoscopic Tel techniques demonstrated that conception rates of 83.3%

and an average litter size of 7.5 were possible in bitches of unknown breeding history.16 These results compare favorably with results from other trials using frozen semen, indicating that there are no undesirable effects from Tel. There are no trials making a direct comparison between surgical insemination and TCI; thus, it is impossible to know if the results are better using Tel, and it is difficult to compare results from different workers because of the multiple factors involved in the successful use of frozen semen.

The ability to do repeat insemination has been reported to increase conception rates and litter size.2, 8, 17 Where the post-thaw motility of the semen is low, repeat inseminations allow more semen to be inseminated over an extended period. Repeat inseminations are also useful if the bitch was difficult to time or not presented in a timely enough manner to permit proper timing.

"Are There Other Uses for the Technique and Equipment?"

The endoscopic equipment carries a significant cost, which may be hard to justify for frozen semen insemination alone; however, the other uses to which it can be put makes it indispensable in any practice with a significant canine reproduction workload.

Although this technique was developed to deposit frozen semen into the uterine lumen, it can be used equally well for all fresh and chilled inseminations and for performing repeat inseminations when appropriate with no apparent stress to the bitch. It is an excellent tool with fresh semen of poor quality, as intrauterine insemination seems to make a positive difference to the outcome. The technique has been used for the hysterographic examination of the bitch and for diagnostic microbiology and cytology.

Recently, Watts et aP4, 15 have used the method to study the intrauterine environment with respect to microbiology and cytology throughout the reproductive cycle of the bitch, giving us valuable research information. Use of this method during anestrus and diestrus requires som modification to the technique. The vaginal mucosa is thinner and more susceptible to damage, and bitches may not tol -rat th ndos op so

'well when not in standing heat. The r quir m nl: fo r s('d nti n haR be '11

reported as well as the need for a ir inflllffi nliol1 . Wilh Ih(' nhi l il In catheterize the cervix and fo llowill l', "I 1111 W,lfl li' 1'\'111'.11'\'1, " OI1l\ '. 11ll'

possibility of dev loping new Ii il l)',I]( lr I II ' 111111 1"1'1 '1 '1 H' I II II' I II', H,,·t! III ', 'rI ,

The endoscope nn niHil II\' Iii t '.! l i lt IP,il l ll l' v, I)',I IIi IIt '1l11 III "I'I I' IIIIII\( '

the prop,f'('H, iUIl 1III 't ltl )', I, 111"11 ' 1,, " .111 1 1" ' 1' I \' 1 11 ,01 I I/ \\' 1,11 11'1 II1 1 Ii 11)', 11 11111 I '

TRANSCERVICA L INSEMINATION TECHNIQUES IN THE BITCH 303

vaginoscopy and cystoscopy. The optics compare favorably with those of other vaginoscopic equipment.

SUMMARY

The benefits of using endoscopic Tel for frozen semen come from being able to achieve the same or better result~ .without the need and risks of general anesthesia and s~rgery. ~he ~bIhty to do all f~esh and chilled inseminations this way WIll certamly Improve co~ceptio~ r~tes without the owner having to make a decision about exp.osmg theIr bItch to the risks of anesthesia and surgery. The other potential uses open up a whole new field for canine theriogenology. Above all, the cllent response to the technique is overwhelmingly positive .. At times the learning process will be discouraging, but the end result IS worth the effort.

The endoscope should not be treated as something speci~l fO.r frozen semen insemination but should be used at every opportumty m order to develop experience and expertise in all situations.

References

'1. Andersen K: Insemination with frozen dog semen based on a new insemination technique. Zuchthygiene 10:1, 1975 . . . ... .

2. Farstad W, Anderson-Berg K: Factors mfluencmg the success rate of artifiCIal msemma-tion with frozen semen in the dog. J Reprod Fertil Suppl 39:289, 1989 .

3. Fontbonne A, Badinand F: Canine artificial insemination with frozen semen: ~ompanson of intravaginal and intrauterine deposition of semen. J Reprod Ferti! Suppl 47:325, 1993 .

4. Fougner JA, Aamdal J, Andersen K: Intrauterine insemination with frozen semen m the Blue Fox. Nord Vet Med 25:144, 1973 .

5. Fllnkqllist B, Lagerstedt A-S, Linde C, et al: Hysterography in the bitch. Vet RadIOI 26:12, 1985

6. Linde-Forsberg C: Achieving canine pregnancy by using frozen or chilled extended semen. Vet Clin North Am Small Anim Pract 21:467, 1991

7. I,inde-Forsberg C: Artificial insemination with fresh, chilled extended, and frozen-thawed semen in the dog. Semin Vet Med Surg 10:48, 1995 .

H. I, inde-Forsberg C, Forsberg M: Fertility in dogs in relation to semen quality and the lim Dnd ' ite of insemination with fresh and frozen semen. J Reprod Fertil Suppl :\ ~:299, '1989 . f

t) . I , ind ~ay III,: F: 'rhe normal endoscopic aflpearance of the caudal reproductive .tract 0

Ih ' Y Ii nnd non- y Ii bitch: P st lit nne endoscopy. J Small Anlffi Pract 24.1,1983 Ill, 0 1,11 ' 'IT, !low ' 11 RI\ , Pi k It BW: II flu n of extender, cryopreservative and semmal

1"'\)( 'I' :lH lng j1r<1('('dllrl'H Oil po~ 1 Ihow I1l ll lilil y of anin p rmatozoa frozen ill straws. '1'11\'1'1(1)',(' 111 110)', 3 1:II S I, IIJIl') . .

I I. 1'IIII ,d ,1 M il , 1, ,,I IIt' I' 1,1\ , 1111\11 11 '11 '" 1,1): 1)I II 'HIIi n\l 'dl " l1 pnH I ('\' rv l ~ :1 1 fold In the anine vllr,l ll ll 1\ 111 I VI' I I'I'H I I' I'IH'I, IIII' \

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I 1,'/1" , l illi" II W'III M Ii ', Wl ll'. l iI 1'1 111 \ ' 1\1, .,, 11111,', 1111 1 III """'I IMI \11 Iii ,' Idll \1 \ 111111111' '"ll l lI il lil l"ll IIII'

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304 WILSON

14. Watts JR, Wright PI, Lee CS: Endometrial cytology of the normal bitch throughout the reproductive cycle. J Small Anirn Pract 39:2, 1998

15. Watts JR, Wright PI, Whithear KC: Uterine, cervical and vaginal microflora of the normal bitch throughout the reproductive cycle. J Small Anim Pract 37:54, 1996

16. Wilson MS: Non surgical intrauterine artificial insemination in bitches using frozen semen. J Reprod Fertil Suppl 47:307, 1993

17. Wilson MS: Some aspects of artificial insemination in the bitch, using frozen semen. MVSc Thesis. Palmerston North, New Zealand, Massey University, 1992


Marion S. Wilson, BVMS, MVSc, MRCVS Glenbred Artificial Breeding Services Ltd

The Glen RD 9 Feilding 5600

New Zealand


UTERINE AND FETAL MONITORING IN THE BITCH

Autumn P. Davidson, DVM

The standard approach to labor management in the bitch has involved client subjective monitoring of behavior, rectal temperature, progression of whelping, and the physical condition of the neonates. Little accurate and timely information is made available to the clinician concerning actual uterine activity or prepartum fetal viability. Telephone consultations between the veterinarian and breeder usually entail interpretation of indirect information, such as time between deliveries, color of vaginal discharge, presence of externally visible abdominal contractions, and occurrence of stillborn puppies.6 Although generally acceptable for the uneventful delivery in a young, healthy bitch, whelping associated with fetal and maternal morbidity and mortality are familiar to most clinicians in reproductive practice.

Many veterinarians also are reluctant to encourage the expense and risk for a potentially unnecessary cesarean section early during labor. With higher-risk pregnancies and valuable litters, better monitoring, similar to that which is the standard of practice in human obstetrics, is desirable.

PERINATAL MONITORING

Recently, such systems for monitoring labor and delivery in the bit h have become commercially available and affordable. These systems i l l"' intend d for use by veterinarians in the clinical setting when evaluat-

III

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306 DAVIDSON

ing a bitch in labor or by breeders at home with veterinary guidance. Their design is based on labor monitoring systems used routinely in human obstetrics?' 11, 13, 14

Inexperienced breeders, and breeders with bitches having histories of whelping difficulties, above-average age (older than 6 years), and small or large litters should be encouraged to use the equipment. With veterinary guidance by telephone, after previous demonstration of equipment in the clink clients at home can perform monitoring of bitches. Such demonstration should take place during a prepartum office visit. Light clipping of the hair coat over the gravid area of the lateral flanks allows proper contact of the uterine sensor and fetal Doppler. Proper technique for the subcutaneous administration of injectable drugs also is taught during the prepartum visit. Calcium gluconate, 10% solution with 0.465 mEq Ca2 +, and oxytocin, 10 United States Pharmacopeia (USP) U/mL can be dispensed in predrawn syringes for later use on veterinary prescription. Specific orders (Fig. 1) concerning the frequency of administration and dosage of medications (calcium and oxytocin) are written for each bitch by the attending veterinarian and/' are faxed to the service. A lateral abdominal radiograph may be obtained at the prepartum visit to estimate litter size best.20

The uterine monitoring system consists of a tocodynomometer (sensor), a recorder, and a modem (Fig. 2). The uterine sensor detects changes in intrauterine and intra-amniotic pressuresY The sensor is strapped over a lightly clipped area of the caudolateral abdomen with an elasticized strap. The recorder of the sensor is worn in a small backpack placed over the caudal shoulder area (Fig. 3). Bitches should be at rest in the whelping box or in a crate during the monitoring sessions. The monitoring units also can be used on gravid queens (Fig. 4). The monitoring equipment is well tolerated (Fig. 5). Subsequent to each recording session, data are transferred from the recorder to the service by a modem connected to the clients' telephones. Fetal Doppler monitoring with acoustic coupling gel is performed with a hand-held unit on bitches in lateral recumbency (Fig. 6). Directing the Doppler perpendicularly over a fetus causes a characteristic amplification of the fetal heart sounds, distinct from maternal arterial or cardiac sounds, which enables determination of fetal heart rates.

Uterine and fetal monitoring should be initiated at least 1 week before predicted whelping dates, and is generally performed twice daily, approximately 12 hours apart. Obstetric personnel (licensed human obstetric nurses) are available 24 hours a day to receive and to int rpret uterine contractile recordings, and subsequently to ommuni a t u h findings by telephone to the attending v t r in , ry lini ii:l l . 11 (, ' a b i t h enters the first stage of labor, th SUb8('q ucn l' frl'qll l' ll r' ()f IIl c ri lll' :lIId fetal monitor.ing i. based 0 11 1:111' r('(" )tn llH' llti ll l inl) of HllCh Ilh/llpl ric I (' I' sonnel and the ntl:('ndi ng v <'I cl' i ll l ll' !. II) ('vdh l! tI 11)', I Ill' 1'1'1))'."" f i()!) o ll ll iJO l' and neoni'l I:nI ('ol l(/ iliol ). (>il ll l, ·l t'I" 1"' 1' l(l ll ll' ,I )'," I II ' I'l lil IIl l iI, ' 1" I"p l'Ol li' CO l) ,tl i.l l l,lt) wil li I II " vl ' Ii ' I'illll l' , 'I IIi,i ,1l1 l 'Olti llllllll l l " dlldll) ', 11I '11 11t! j, ,, l()I ' II II )I Ii /111 i l ll',

UTERINE AND FETAL MONITORING IN THE BITCH 307

WhelpWise ™ Veterinary Orders Please circle all that apply

Client Client Phone' _ ______ Date, _______ _ Anima-l-N-am-e------ - - Breed, _ ___ ________ Wt .. ____ _

1. Initiate the Whelp Wise™ service. Instruct client in use of equipment. Encourage client to monitor uterine contractions twice daily, preferably 1 0 to 12 hours apart. At the onset of an actIve labor pattern, chent and Whelp Wise staff will detellline the frequency and duration of subsequent monitor sessions.

Notify me of onset of labor: YES NO After hours: YES NO

2. In the presence of inertia as documented by the external uterine contraction monitor, begin labor augmentation per protocol. YES NO Notify me before beginning medications: YES NO

3. All medication doses are based on the uterine contraction pattern, and used to treat inertia only.

Medication will not be given in the presence of a strong, regular contraction pattern Oxytocin: __ to ___ UNITS administered Sub Q or 1M every minutes (Usual dose .25 to 4 units every 30-90 min.) to maintain an adequate uterine contraction pattern. Calphosan Solution (lOOmg/lOcc or a 1 % calcium solution) ee's, subcutaneously every

hrs. (Usual dose: Y, cc/pound every 4-6 hours.) . Dopram: I-S gtts PO or 1M as a respiratory stimulant for depressed puppies. May be repeated m 15 to 20 minutes. Dosage will be based on puppy weight and level of depression . CicaDout shot of: , after deliveries are complete.

Suggested breakdown: ........ . Oxytocin: 2 syringes with .5 units (oTIe half umt), 3 synnges With 1 UnIt, 3 syrInges .':lth 2 um.ts, 2 synng~s wlth 3 lIll its. In breeds over 701bs; add 2 syringes with 4 units, breeds over 100lbs; add I addltlOnal syrmge of 5 UllltS. Calci um: 112 cclI 0 pounds drawn into 3 syringes. Example: Dog's weight 30 pounds; 3 syringes of I.Scc's Oopram : .3 ce, in a TB syringe.

,\. Encourage client to monitor the fetal heart rates a minimum of once a day prior to labor, and every 1-2 hours or more I'l'cquently during active labor. Notify me if decelerations or absence of fetal heart rates are noted. Recommend that the ' Iion! assess the fetal heart rates prior to administration of any medication.

S. I f the case being monitored is a planned cesarean section, notify me at the onset of labor.

G. NOlify me of the outcomes at the conclusion of service by --"hone _ fax

Olhcl' Instructions:

HigHu t,II I'C V eterinaria nl _____________ _ ( 'lI nie Nll'IlI--C----------- Address _ ____________ _ _

('lI n ie Phonc ______ Fax. ________ After honrs _ _ ______ _ _

I' PI' P r d b for whelping during the pre-whelp consultation, faxed to I1 V d In th I tI nt r cord. Orders Indicate the interval at which the

to b( II tlillor! , pMI nl 111" tory nd p rtinent findings, and drug

308 DAVIDSON

Figure 2. Whelping monitoring equipment includes a sensor, tran,sducer, modem, and hand-held Doppler.

Figure 3. Uterine monitor placed over a lightly clipped region of the canine caudolater abdomen, with the recorder in a harness worn over the scapula


Figure 4. Uterine monitor placed on a gravid queen. The recorder is situated adjacent to the crate.

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310 DAVIDSON

Figure 6. Hand-held fetal Doppler directed perpendicular to a fetus' trunk.

The administration of medications is initiated as indicated by monitoring information, and is initiated with authorization from only the attending veterinary clinician. Unresponsive uterine inertia, . obstructive dystocia, aberrant uterine contractile patterns, or progr~ssive fetal distress without response to medical management are indications for cesarean section.

The active, early management of labor is accepted in human obstetrics as a method of reducing dystocia and increasing vaginal deliveries without increased maternal or neonatal morbidity.lO Key to successful obstetrics is an accurate diagnosis of the onset of labor, facilitated in human obstetrics by patient communication.12 Predicting parturition in the bitch is straightforward if ovulation timing has been performed . Whelping should occur 56 to 58 days from the first day of diestrus or 64 to 66 days from the initial rise in progesterone above baseline, or from the day of the luteinizing hormone surg . Without ovul ation tin -ing, whelping can occur 58 to 72 days from b n.'('d ing, 111 :1 1 ing th ' li Se of uterine monitoring useful in iden tify ing the' n ll :;I' 1 or I l\ b ()l". ~·"

Elevated prostagland ins fi n 11(' dd (', 'lI ·d i l l 11 11' lllt· !'i I H' Vl'i 11 ' I ~~ hours before the onsel' of . 1:11\1' I 1.11 )( 11', 111 d lll illl ' i d l lllli wll h , I .1 "( '1111 ,,1 11 prog te r OIl C ivv(' I1'1 10 1" 111 111 ,1 11 '11/'.1 1111 oli id , I dlll l' III IHld y 11'11\1'1' 1'11

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not highly accurate in the range of 2 to 3 ng/mL, and the 24-hour turnaround time for quantitative progesterone testing submitted to a commercial laboratory makes the reliability of predicting impending labor from progesterone levels poor. A temperature drop of 99° F or less often, but not always, occurs 24 hours before the onset of labor. Normal stage I labor is characterized by intermittent uterine contractions associated with cervical dilation and behavioral changes. Normal stage II labor has intensified uterine contractions accompanied by abdominal efforts and Ferguson's reflex, resulting in fetal expulsion. Normal stage III labor is characterized by placental expulsion.! The length and quality of human labor correlates closely with the number of live-born, vigorous neonates.7

The canine uterus exhibits characteristic patterns of activity during late gestation and labor, varying in strength and frequency,17· 18 Interpretation of the contractile pattern in strips produced by the uterine monitoring system requires training and experience. Commercially available monitoring devices currently transmit recorded information by modem to obstetric personnel capable of interpretation and subsequent consultation with the attending veterinary clinician. Interested veterinary clinicians or technicians could develop this expertise.

The use of a uterine monitor permits proactive identification of labor for planned cesarean sections when gestational length is not accurately known and surgical intervention is deemed necessary because of maternal-fetal mismatch.3• 4. 8. 9 The presence of fetal distress is reflected by sustained deceleration of the heart rates. Normal Beagles at term have heart rates at least twice the maternal rate,17 Decelerations associ" ted with uterine contractions suggest mismatch of the fetus and dam or fetal malposition, malpresentation, or malposture. Transient acceleralions occur with normal fetal movement.16• 19

THERAPEUTICS

The use of uterine and fetal monitors allows the veterinary clinician 10 detect and monitor labor and to manage labor medically with insight. , I'h administration of calcium gluconate and oxytocin can be directed Ind tailored based on the results of monitoring. Generally, the adminis-

11'r. tion of calcium gluconate increases the strength of myometrial activity, li nd oxy to in .increases the frequency of myometrial contractions. Cal,'illl11 glu onate, 10%" is given when ineffective, weak uterine contrac-11(1)1'1 <l re d ,t I' d. xyt 'in is administered when uterine contractions , II 'l ' I('HS fre'q lien I' 1'11 <111 'xp t 'd for th sta of labor and when fetal 111'11 1'1 l'nll'S Ilrv I 1() l'Ill , li , Suh Innli nli y low r than traditional doses of ox IOI 'i" l i n ' l'ff(l\'l iv (' ill in'l )f'()vi nl'. II I(' qll ll lil of 111 Ol11ctri al ontracI ( li lt \. Il i/', llt' l' d ill " I1 (I I II 'I y l (H'1 1i , " ' 1I11'I\V" llI lll holll \' ,' 1\ 11 cn ll ,'l Ina ni , 111' 111 '( '1 (. liI (' I'I III ' 1'11,111 ' 11 l ililil l 11 11 11 1'111111 11 '1111 1 111 ' 11'1 II II Y/'," " I il ljll Iy hy

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312 DAVIDSON

with elevated baseline levels of contractility compromIsmg placental blood supply, or a uterine obstructive pattern negate further use of calcium gluconate or oxytocin.

SUMMARY

The use of uterine and fetal monitoring improves the outcome of canine obstetrics. Much of the guesswork of managing whelping can be eliminated. At normal term, absolute indications for cesarean section are detected with monitoring, before multiple fetal deaths or any serious maternal compromise occurs. Bitches with previous history of cesarean section may be able to whelp vaginally successfully, having medical intervention based on monitoring. The anxiety level of owners during whelping is diminished, and the level of participation of the veterinarian improves.

References

1. Bennett D: Canine dystocia: A review of the literature. J Small Anim Pract 15:101-117,1974

2. Concannon PW, McCann JP, Temple M: Biology and endocrinology of ovulation, pregnancy, and parturition in the dog. J Reprod Fertil Suppl 39:3-25, 1989

3. Darvelid AW, Linde-Forsberg C: Dystocia in the bitch: A retrospective study of 182 cases. J Small Anim Pract 35:402-407, 1994

4. Eneroth A, Linde-Forsberg C, Uhlhorn M, et al: Radiographic pelvimetry for assessment of dystocia in bitches: A clinical study in two terrier breeds. J Small Anim Pract 40:257-264, 1999

5. Feldman EC, Nelson RW: Canine reproduction. In Veterinary Reproduction and Endocrinology. Philadelphia, WB Saunders, 1996, pp 567-570

6. Freak MJ: Practitioners- breeders' approach to canine parturition. Vet Rec 96:303-308, 1975 .

7. Friedman EA: Use of labor pattern as a management guide. J Reprod Med 8:57-60, 1968 8. Gaudet DA: Retrospective study of 128 cases of canine dystocia. J Am Anim Hosp

Assoc 21:813- 818, 1985 9. Gaudet DA, Kitchell BE: Canine dystocia. Compend Contin Educ Small Anim Pract

7:1406-1418,1985 10. Lopez-Zeno JA, Peaceman AM, Adashek JA, et al: A controlled trial of a program for

the active management of labor. N Engl J Med 326:450-454,1992 11. Neutra RR, Fienberg SE, Greenland S, et al: Effect of fetal monitoring on neonata l

death rates. N Engl J Med 299:324-326, 1978 12. Sharpe WS, Hauptman, JG, Dennis JS: Detrusor atony of the urinary bladder fo ll ow ing

prolonged dystocia in a dog. J Am Anim Hosp Assoc 29:299-302, 1993 13. Shenker L, Post RC, Seiler JS: Routine electronic monitoring of f ta l h art ra t' and

uterine activity during labour. Obstet Gynecol 46: '185- 18 , '1975 14. Snyder KC, Yoches CC: A retrospective SU111111 Ar of!'iO ,'n llin,' prvgl,n IWilIK. III WI

Watch, Handout for Veterinarians, '19 7 15. Taverne MA, Naaktgebor 11 , 1 \l ~nl'KH l' r II, (Ii ,II : M)'IlIlli 'II'1. 11 1'1('(' 11'11 '1 ,1 II, 'llvlly " '1.1

plasma concentra ~ion s of I1I'OI\I'lilI ' I'I1I1" , "11 11'111'0" ' 11 1, ","1 I 1\ \, Inl'l II dlll 'lli )', lil li ' I "'''1', 1 I, ll lI 'y and par turiliol1 ill I'hl' 11,1'11 11 1111'" " I,., 11 1,,1 1 ~ " I '"11 1 ' I II ' '', 11 11/ 1'1'/' /

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17. van der Weyden Gc, Taverne MA, Dieleman SJ, et al: Physiological aspects of pregnancy and parturition in dogs. J Reprod Fertil Suppl 211-224, 1989

18. van der Weyden, GC, Taverne, MA, Okkens AC, et al: The intrauterine position of canine fetuses and their sequence of expulsion at birth. J Small Anim Pract 22:503-510, 1981

19. Verstegen JP, Silva LD, Onclin K, et al: Echocardiographic study of heart rate in dog and cat fetuses in utero. J Reprod Fertil Suppl 47:175-189, 1993

20. Wallace MS: Management of parturition and problems of the periparturient period of dogs and cats. Seminars in Veterinary Medicine and Surgery (Small Animal) 9:28-37, 1994

Address reprint requests to Autumn P. Davidson, DVM

Small Animal Clinic Veterinary Medical Teaching Hospital

1 Shields Avenue University of California, Davis

Davis, CA 95616



PERIPARTURIENT AND NEONATAL ANESTHESIA

Peter J. Pascoe, BVSc, and Paula F. Moon, DVM

Patients presented in the periparturient period may need surgery for nonobstetric reasons, they may be undergoing hysterectomy, they may be undergoing an elective cesarean section, or they may need an emergency cesarean section. In all these circumstances, it is important to recognize that the dam has undergone some physiologic changes during pregnancy that alter the response to anesthesia. In addition, the clinician must consider the fate of the neonates and be able to optimize the ,1I1esthetic technique for their welfare. Extensive human data have been published on the action of and outcome from anesthesia; however, h 'cause of species and technical differences, veterinarians may not be db le to directly apply the knowledge gained from human obstetric ('xperiences. For the veterinarian, many review articles have been pubI i:-; hed,6, 12, 24, 32, 35, 39, 49, 57, 69 but there are few data that support the use of one technique over another,31,56 This has resulted in tremendous variat ion in the perioperative management of such cases and a continued He" rch for the "best technique."

PHYSIOLOGIC CHANGES AND THEIR IMPACT ON ANESTHESIA

Th altered physiologic state of the pregnant patient results in 1 111' 'inl pcrioperative problems concerning the choice of anesthetic tech-

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316 PASCOE & MOON

nique.15 The most important changes that affect anesthetic management are summarized in Table 1 and are provided in more detail here.

Respiratory Changes

Oxygen desaturation occurs more easily during pregnancy?4 Ventilatory changes include a decrease in functional residual capacity (FRC) and total lung volume and an increase in minute ventilation. The decreased FRC relative to alveolar closing capacity suggests that atelectasis may occur more readily than in the nonpregnant animal; in fact, in 50% of awake healthy pregnant women, airway closure developed during normal ventilation? Combined with higher oxygen requirements, pregnant animals are extremely vulnerable to hypoxemia under anesthesia. An especially critical time is during induction, when the patient is still breathing room air and variable periods of apnea are likely to occur from the anesthetic induction drugs. Hypoventilation on room air may cause not only fetal hypoxia but fetal acidosis. In people, it has been shown that anesthetized apneic pregnant women desaturate to an arterial hemoglobin saturation of 95% in less than half the time taken by nonpregnant women when seated at a 45° angle (156 vs 331 seconds).4 Preoxygenation via a face mask for 3 to 5 minutes at a rate of 4 to 6 L/ min decreases the likelihood of hypoxia. Intermittent sighs during surgery to re-expand the lungs may decrease the severity of atelectasis. Pregnant women have an increased minute ventilation with a consequent reduction in the normal Paco2 (26- 32 mm Hg) and an increased sensitivity to changes in Pacoz.47 If further hyperventilation (Paco2 < 22 mm Hg) occurs as a result of maternal stress or excessive positivepressure ventilation, there may be negative effects on the fetus .37, 63 Hyperventilation, with alkalosis, shifts the oxygen- hemoglobin dissociation curve to the left, causing less oxygen to be released to ' the fetus (Bohr effect).16 This effect cannot explain the whole decrease in fetal oxygenation; thus, hyperventilation must also cause a decrease in uterine blood flow. It is not certain if this is caused by a direct effect on uterine vessels or by a general effect on cardiac output.50, 63 Although it is important to preoxygenate, provide supplemental oxygen throughout the procedure, and assist or control ventilation, care must be taken not to hyperventilate the patient. The addition of positive end-expiratory pressure or continuous positive airway pressure to positive-pre sure ventilation may further decrease the risk of atelectasis, but the circulatory depression associated with this approach mu t b balan 'd agai nst the potential benefit in gas exchange. Pul oximct rs nd "pnom'I' rs are useful noninvasive monitor to val LI m t 0 'yg n s< lLi ratio n DI1 I o li t'

quacy of ventilation..

Neurologic Chang s

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endorphins,34, 85 which are elevated during pregnancy. The potency of inhalants is increased for halothane (25%) and isoflurane (28%-40%).33,70 In addition, uptake of inhalant anesthetics is more rapidly achieved because of the decreased FRC and increased minute ventilation. The combination of a more rapid uptake of inhalant anesthetics and a decreased anesthetic requirement may lead to anesthetic overdose. Drugs must be titrated slowly, and depth of anesthesia needs to be carefully and frequently assessed. A further indicator that there are significant changes in the nervous system during pregnancy is that there is a change in the sensitivity to local anesthetics.14, 22, 30 The onset of a local anesthetic is faster in the pregnant animal, and the block lasts longer with lower concentrations of local anesthetic?5

Cardiovascular Changes

Changes in cardiovascular parameters recorded during pregnancy in Beagles are given in Table 2.13 Systemic blood pressure and right and left atrial pressures decrease, although heart rate increases slightly. Cardiac output and blood volume are increased to provide adequate blood flow to the fetus (but note that in the data from Beagles, the blood volume per kilogram does not alter up to 46 days of gestation) . This increased cardiac output mitigates (to some extent) the respiratory changes by reducing the rate of induction with an inhalant anesthetic. Plasma volume increases more than red blood cell volume, leading to a relative "anemia of pregnancy". This anemia is correlated with the number of puppies the dam is carrying, with greater changes seen as the number increases.45 Furthermore, uteroplacental perfusion is pressure dependent, and autoregulation of blood flow to the fetus does not occur. The consequence is that uterine blood flow is directly proportional to the arterial- venous uterine blood pressure difference and inversely proportional to uterine vascular resistance. Either hypotension (e.g., anesthetic depression, patient condition, intraoperative fluid losses) or increased vascular resistance (e.g., pain, fear, excitement, shock) can

Table 2. CHANGES IN CARDIOVASCULAR VALUES DURING PREGNANCY IN BEAGLES

Blood Left Atrial Right Atrial Gestational Heart Rate Pressure Pressure Pressure Blood Volume Age (days) (bpm) (mm Hg) (mm Hg) (mm Hg) (mL)

Nonpregnant 74 112 lO.9 5.5 1772 (76 IId ,/ kg) <39 97 11 3 7.8 2, 1 40-46 97 10< 7.4 .:' 17 ('Ill 1111. / 1-1») 47-53 ·' ()7 lOll, '/.II r, I~) 54-60 II G IIl I 'I ,ll ~J ,~I

( I I,I,'X,) 10%) 'Ht'{I) 'd",,)

11111111 I IHlp l·~ V!" \ ,111 11 111" IIHldIH H' 1I I 'I II II1111 Hl !l 11 , , 111I 1'11 ''''' 1111 .II II1I\PI 1II Itl PHll ll lil IH tIl IH\1I 111

wil l i III " II " "p,II ,1I11 oI "I\~ I " I, "11,, ,,'11' II , "1 11'1 1\ d,oI '1'11 11 "III Irol 'l 1'1111 , ·111, 1"'"111 11 '""

PERLPARTURIENT AND NEONATAL ANESTHESIA 319

decrease uterine blood flow and adversely affect the fetus . In women, hypotension can also occur from aortocaval compression by the fetus . As a result, women are often positioned in lateral recumbency or with a lateral tilt. In dogs, however, dorsoventral positioning did not cause any more hypotension than lateral positioning or positioning at a 10° or 15° oblique angle.2, 76, 77 Two of these studies measured systemic blood pressures as their main indicators of cardiovascular change, and it is recognized that regional flows could be altered without a change in pressure. The third study looked at blood flow and found normal venous return even when the posterior vena cava was ligated.2 Given these data suggesting a much greater available collateral circulation and the anatomic differences between human beings and small animals, positioning the animal in dorsal recumbency is less likely to have a negative effect. Finally, a delay in compensatory cardiovascular reflexes in response to blood loss and hypovolemia may be present during pregnancy,B and pregnant patients may be less responsive to therapy with vasopressors or chronotropic drugs. 15 With epidural anesthesia, it has also been shown that uterine blood flow can remain decreased in women despite therapy that treats maternal hypotension.46

Collectively, these data justify having aggressive cardiovascular support as an integral part of the anesthetic protocol. Intravenous (IV) fluids should be administered to all pregnant animals during surgery as well as before and after surgery in some critical cases. Whether or not the Lype of fluid is important remains unclear, although there is some evidence in women that colloids result in a lower incidence of maternal hypotension than isotonic crystalloids.46 Mild hypotension (systolic bl.ood pressure> 90 mm Hg and < 100 mm Hg) should be treated i rnmediately by increasing the rate of fluid administration. Changing the maintenance anesthetic protocol to include analgesic agents such as r ntanyl (3-5 j.Lg/kg IV) permits a decrease in inhalant concentrations nnd may improve cardiovascular function. Refractory hypotension should be treated with ephedrine (0.03- 0.1 mg/kg IV) as the first choice or with dopamine (1-5 j.Lg/kg/min IV) or dobutamine (1- 5 j.Lg/kg/min I V). Ephedrine is unusual in that it preserves uterine blood flow better I han other IX] agonists, and it has recently been suggested that this drug , Ii mulates release of nitric oxide in uterine vessels, hence reducing the v lHO onstrictor effect of alpha-agonism.52 Dopamine must be titrated ( '.II' ,fu lly as it can either increase or decrease organ blood flow deI'vl1tl ing on the dose. At rates greater than or equal to 10 j.Lg/kg/min, dll pu rn inc au es systemic vasoconstriction with potentially decreased ( iI 'r, 1n I "fusion. Dobutamine has not been extensively studied in obstetI' ( ' 1111('HlhcH i8 but ShOll ld incr ase uterine blood flow by increasing I y k ill iv p rt'HH(II ·VH wifholl t vaso on tric tion. Dopamine and dobutamine dl'I ' I" ·.l t li ld 11 11'I'ill(' Id lH1l 1 nnw a l dOH'S of 4 to 40 j.Lg/kg/rn in in pregnant I'W I 'II '" fll l\ l :il llJl rltI (li d y 1)(' 110 I'd 10 11'(' d' pt'I'HiHt('n l' nOI1 I'I'HpOnH ive hyl' II II 'l ll riOIl 1': 1"1 11'1,111 1111 ' \l1 'dl l loilil'ldl dl'( ' I'I 'HH('tl 111 (If 'i ll( ' 1,1 ()()d fl llw 111,d dll'l tid Il lrl y III' IlI lI'd III ii I" 11 11' II I· pi II II' 111 1111 ",, ' II I 1' 111 11/ 11'll p l l " lil l II l iI ,II I I

320 PAS E & MOON

Pregnancy also induces a number of gastrointestinal changes, the most important of which increase the likelihood of regurgitation. Lower esophageal sphincter tone is decreased, and intragastric pressure rises. An increased amount of gastrin is produced by the fetus and the placenta, leading to increased production of gastric acid.47 Labor is thought to prolong gastric emptying. These factors combined put the parturient at greater risk for regurgitation, and if this occurs, there may be more pulmonary damage from aspiration (greater volume, low pH).

Premedication of a painful (i.e., in labor), anxious, aggressive, or fractious patient may be beneficial in decreasing the maternal stress response (elevated cortisol and catecholamine release) and aid in uterine perfusion. These stress hormones cause constriction of uterine vessels and increase uterine vascular resistance. Premedication also allows clipping before anesthetic induction and better tolerance of the oxygen mask. With few exceptions, the type of drug used for premedication does not seem to affect fetal outcome provided that appropriate doses and effects on the dam's condition are considered. 59

ANESTHESIA FOR THE PERIPARTURIENT PATIENT REQUIRING URGENT NONOBSTETRIC CARE

The main factors to consider in this type of patient would be to minimize the amount of stress experienced by the animal (promotes early onset of parturition) and to try to avoid hypoxia, hyperventilation, uterine hypotension, and anemia. These may be difficult things to accomplish, because it is likely that the patient may already be stressed; if it has suffered from a traumatic episode, it may also have lost blood and thus be hypotensive and anemic. Given these issues, it is extremely important to resuscitate the patient and provide analgesics so as to minimize stress before proceeding with any anesthetic. Blood transfusions should be considered at a higher hematocrit (e.g., 25%) than in the nonpregnant patient, and the blood should ideally be typed and crossmatched before transfusion. Once the animal is stable, the anesthetic technique should aim to avoid further hypotension (e.g., no acepromazine) and provide excellent analgesia (e.g., opioids). The clinician should consider the use of local anesthetic techniques and epidural opioids or local anesthetics to further minimize the stress response to the surgical intervention.71, 79 The use of drugs that cross the placental barrier i not of great concern, because they are returned to the dam as she recovers from the anesthetic. At the late stage of pregnancy, iti un likel y that <;tny of the anesthetics have teratogenic eft ts.

ANESTHESIA FOR THE PREGNANT PATIENT UNDERGOING HYSTERCTOMY

In Ihi il, illlllllllll , 1111 ' 11 ' 11 1'11 '11111 ' )',1 il l I/" l il l I! ' 11'IlIilll llll ,lI , 1111111111 ' .1 III

I hOld" \II ' III lilli ' 11 1,'1 1· 11,, ' 111 II I 11 11' 11' 11 Il ld l 11 11 ' \ 11111 1'1 ' 1' 11111 .1 110" I,d

PERlPARTURlENT AND NEONATAL ANESTHESIA 321

without further distress. All the physiologic changes mentioned previously need to be accounted for in providing the best anesthetic for the dam, but the drugs used should be given in sufficient doses to anesthetize the fetuses. This happens with normal induction doses of most anesthetics, but it might be appropriate to use drugs with a longer duration of action. For this procedure, it would be better to use thiopental or ketamine rather than propofol, because thiopental and ketamine remain in the fetus for a longer period. Once an inhalant has been started, it is more likely to anesthetize the fetuses if it has had more time to diffuse into the uterus; thus, there need be no effort made to preclip the dam or to rush into the surgical procedure. Immediately after the uterus has been removed from the dam, the fetuses should be euthanatized by an overdose of pentobarbital intraperitoneally (IP) or IV via the umbilical vein.

CESAREAN SECTION

Preparation of the Patient

For an elective or emergency cesarean section, the delivery of live vigorous puppies or kittens and the rapid recovery of the dam are the ultimate goals. Once a decision has been made to carry out the cesarean I-)cction, it is important to proceed with these factors in mind. At a minimum, the dam should be given a careful physical examination with f articular attention to cardiopulmonary function. She has had to adapt lo the growth of her fetuses in the ways indicated previously, and these 'hanges may put significant stress on the cardiopulmonary system. I}ecause vomiting and aspiration may occur during labor, the lungs should be auscultated carefully so that treatment can be initiated if this h<ls occurred. A careful evaluation of hydration status should be made I'lO that any deficits can be addressed before surgery. As part of the I'xmnination, it is ideal to use ultrasound to check on the viability of the fduses. This may also allow the measurement of fetal heart rate, which i, . an indicator of fetal well-being. In the periparturient period, the I'ilrd iac output of the fetus/neonate is mainly dependent on heart rate, Ill'cau e the right ventricle is relatively stiff (low compliance) and the 1IIItonomi nervous system is immature (minimal inotropic response to 1',1 1(\ hola ll1ine ). If the fetuses have heart rates above 200 beats per lili nut ', th 'yare probably doing well, but lower heart rates may indicate 111 1 inndqllnt \ ardi a output with resultant stress and the need to 1"'(I"I'I'd 1\10 1" 1"1) idl y. A blood SO'ltnilc +lOuld be drawn from the dam; ,11 . 1 lltillillllllll , il . 11(111111 Iw \'lll'cl vti fUI" Ill'mntn ri t, to tal protein, glucose, I n Ivil 1111 / d lld hl(1(1d 111'( '11 IIIII'Il)','· II . I "1'1'1 '11 , ,'d 1'.111 ('1).'1' or ('::I I illm on en-11 111 11 111/ 1 lilllidd I,, ' 1I'I 'I 1II ,d 1ll'i 11 1'I' III ')',I ' I'Y, II"I" lIl fh' 1111 ' hl'1l1.l l o(, f'il i8 I' 1" '1 1, ," III 1,1, 111\ 1' 1 1111111 I",' 11 11111 11 " 11' 11' 11' 11 1'1' 1'1111 /',1'/1 1(\ 1' IlIllljll'( ' /', II , lIiI

,lI ti lll ldr, \'11 1111 ' I 11 1111 ' 11 11 1111 11 1 11111 /'," 111 01\ 111111 Iii, ' .11 ' '' \' <11 ,, 111 111 1'1 1.1 111

),, 111 101 1' 111 11\' I" , I il l " I ii 11 11 . il l, III III I ' 11 [ ilil Ili l' ," d\ 111 ·h ' i ll I II' 1I / 1'11t! I

322 PASCOE & MOON

the fetuses have been dead long enough to produce gas. A radiograph does not enable one to differentiate live from freshly dead fetuses. If a radiograph is taken, it is a good idea to try to include the stomach in the picture so as to assess the amount of food present. In human obstetric practice, it has been recognized for a long time that labor alters gastric motility and that patients undergoing cesarean section are at increased risk of developing aspiration pneumonia.54 There was no indication that this was the case in veterinary medicine until new data revealed this as a distinct possibility. 56 In this study, five of nine (56%) maternal deaths after canine cesarean section were attributed to pneumonia. The study was done prospectively, but it was not designed to determine at what stage this pneumonia developed. Nevertheless, this is a much higher incidence than in the general population of anesthetized patients and suggests that there might be a concern with regard to aspiration pneumonia during cesarean section. The owner should be questioned about recent food intake and for a possible history of vomiting before presentation. Any radiographic evidence of a full stomach would be an indication to use a technique that would allow rapid control '6f the airway to prevent aspiration during induction. Vomiting and regurgitation during recovery are also possible; thus, the endotracheal tube should remain in place until adequate control of the airway is regained by the patient. If there is any stained mucus in the endotracheal tube at extubation, the animal should be treated with antibiotics for 4 to 5 days and monitored carefully for signs of pneumonia.

As indicated previously, it is necessary to provide aggressive cardiovascular support during cesarean section. Therefore an IV catheter should be placed as soon as possible, and appropriate fluid therapy should be started.

Part of the success in achieving lively active neonates is to give them as little anesthetic as possible and to be prepared to resuscitate and support them should this be necessary. The first goal can be promoted by shortening the time from induction to removal of the puppies or kittens, and this means getting the animal clipped and prepared as much as possible before induction. All the surgical equipment should be out and ready, and if the surgeon has already scrubbed and is ready, this can also speed delivery. Finally, it is necessary to set up equipment (see article on neonatal critical care) and have personnel available to receive, care for, and resuscitate the neonates as needed. Ideally, there should b one person per newborn animal so that immediate care can b given a ' soon as the puppy or kitten is delivered. Although this may not a lw ays be feasible, the clinician should be creative in achieving thi s nd.

Anesthesia

0111' ('111'1'( ' 111 1,lit ' pi IIIO w l"d )',1' w illi 11 ')',III 'd III 11)1' 111 ' 111 '1 II IlIld

"ill'n ll , IIi' l il l y 1'111111' 11 IIj II 11 '111 11 II III 11111 1\11 11 111 1111 11 111 ,11 wlilt 1111 ' 111111111 11 1

1 I1 11 IIVI I 111 1011 ' 111 1 1t11111 11l1 ' I' ,11 1'11 11 1'1 111 111 1."',1 ' 1\11 " 1111 11 1 11 11' " )', 1\"'11 II I

PERIPARTURIENT AND NEONATAL ANESTHESIA 323

some canine data, but there is a paucity of information on feline cesarean section, In one study of feline dystocia, 123 cesarean sections were performed, but no outcome data were given on maternal or fetal survival,27 and in another study detailing en bloc resection of the uterus and ovaries, 26 cats underwent cesarean section.82 From this group of cats, there was a 58% incidence of stillbirths and, during the first week, a 10% mortality of the kittens born alive. One dam died 9 days after surgery as the result of an ongoing coagulopathy. Given this lack of scientific information, the technique that is chosen for cesarean section depends on the ~r~gs and facilities available and the knowledge and skIlls of the prachhoner. For an emergency cesarean section, it may be better to use a familiar technique rather than one that you have not used before even if the familiar technique is less than ideal for this purpose. The mos~ comprehensive study of cesarean section in dogs to date was prospechve and analyzed data from 809 operations.56 The only two drugs associated with a lower puppy mortality rate were isoflurane and prop'ofol, and the o.nly two drugs with a negative effect on puppy survlVal were xylazme and methoxyflurane. The measure of success (puppy mortality) in this study is an important one but may miss some of the more subtle effects associated with different anesthetic techniques. What follows is an attempt to point out the concerns with different approaches, recognizing that the information provided is biased by the .1 uthors' experience (Table 3).

The first general statement to be made with regard to placental I ransfer of drugs is that if the drug crosses the blood-brain barrier, it crosses the placental barrier. This means that all drugs used as sedatives, I ranquilize~s, centrally acting analgesics, and anesthetics cross the placental barner and have an effect on the neonate. The approaches that 1'. n be used to minimize the effects on the neonate include the following:

1. Use local anesthetics and minimize systemic absorption. 2. Use the smallest dose possible to get the desired effect on the

dam. As indicated previously, the periparturient animal has a lower requirement for anesthetics, and labor and fatigue may further decrease the doses needed. These things suggest that a~e thetic dose should be titrated carefully for each patient (one eIghth- one fourth of the calculated dose).

3. Us d rugs that have a short duration of action and are rapidly m ' tabolized by the dam. The neonate has a limited ability to lTl ' tnbo liz drugs; thus, any drug remaining in the fetus at the lim' of d li v ry may per ist for longer than expected in the "dull. If I"Iw I. m ITl ctabo liz d th d rug rapidly, her blood concenI ro1 l iOI)H (k uvns(' qllicll ~lI'd fav or I' abs rption of the drug from 1111' I"du,', PrOl'Orol iH i l g()()d (' 111111 It' of Hllch n d ru g.

d, 1 )1 1' lil'll )',r! Ih ll l , 11 '1' l'I'v l' I'n l/tl l ', Tid: IlH ''\IlS 111111 ('\1 1' 11 [hollgh Ihe dill )" 111 ", 11 1111'111,, 11 1 ii , ', 1/ , , ,11, ', 1 , '11 11 I ... , II 11 11)',1 IId y" ,d ,

I, MII IIIII /I' 111i ' l i lli " 111 .1 1 1111 ' d , l lll I I I' l 'I,,"'d 111 11111 11 111 11 01 11 , ' 11111 ' 1 , '

1Ii Ii I l' "Ij" II V 11 11 11'1', 1" 1 III dl" 1"1 111' IIII' 0111 /11' II II'd (I' )', , 111 11 1111,111 1 I

(/)

~ o o z <{

!II I: ... Q) U I: o

~ I: o :;:; ::l a:s U

~ D..

(/) 'E C} :!:5 g ~~

>oJ: u ...

Z I: 0 o ~~ 13 Q; I: W E'(/) w z <{ w a: <{ (/) w o a: o LL 'E <{ .!!:!:5 Ui "l;jiQ W D.. Q)

I >oJ: I- U"C (/) I: 0 W Q) 0 ~ ~CJ a: ~.!: o w LL (/) W ::J Q z I o W I-o W o Z W ::2! ::2! o o ~

PERIPARTURIENT AND NEON ATAL ANESTHESIA 325

light P lane of anesthesia; use a local anesthetic technique in conjunction with the inhalant).

Pr medication

Premedication mayor may not be necessary depending on the state III I h ' dam. An animal that has been in labor for 24 hours may be 11I'.ll'ing exhaustion and may be getting toxic, in which case it needs no IlIt'l ll l'dication. On the other hand, a vicious dog or ferocious cat pre-"llll'd for an elective cesarean section may need a high dose of drug so

[11,11 the veterinarian is able to proceed. Apart from the need to minimize IIloIlt'rna l distress and provide analgesia, premedication often reduces IIII' dose of induction and maintenance drugs required for general anes-1ll"rd,l, thus helping to decrease exposure of the fetuses to more de-1"I'HHi ng drugs.

!\ccpromazine was not associated with an increase in maternal or II' tlll.l lnl mortality,56 but it is a potent aI-antagonist and a long-acting 011111', lhat requires hepatic metabolism. This is not an ideal drug to give 11\1' .loI ll1 b cause of hypotension or to give the puppies, because the dlli)" Ills ts longer (immature hepatic metabolism) in the puppies than in III' dol l\) .

Mosl I r gnant dogs and cats respond well to opioids, and routine ,1,1' 1'/ of th se drugs provide analgesia and sedation. The f-L-opioid 1)',llI li NIH ( .g., morphine, meperidine, methadone, oxymorphone, fenI 1I1~ I) ,11'( ' mOI-e effective at reducing the doses of induction and mainte-1101111 '1' dnl gs than the opioid agonist/antagonists (e.g., butorphanol).

\y l.l y- in and other a2-agonists are not recommended for cesarean , , 111111. I.v;ine is associated with a higher mortality in small animals 1I11I111I 1'l'd with other anesthetics17 and, more specifically, with a higher 1""loi l. II Ill ()rtality after cesarean section in the dog.59 In awake healthy

1'1' )',1 lo ll iI ,'wes, a clinical dose of xylazine produced adverse fetal re-11111111 'ti, i ii I' '' Lding bradycardia, hypertension, and hypoxemia, which

," I III11 't I I (I I' It.p to 20 minutes after administration?3 It is likely that the 1,"1"11 1 IV , Ill\nn ist effects of medetomidine and romifidine have equally III '"ill t' t'lk\'ts on uterine blood flow. Even at doses of 1 f-Lg/kg (adminI 1,It ,d IV), II 'ledetomidine induced a 60% to 70% decrease in cardiac II 11'1 II III HI ,I 00% increase in systemic vascular resistance?8 A study in " ,ll 11 /1 II )', 110 )-Lg/kg of medetomidine administered intramuscularly

I 11111 1,1 1 111 11 11' r ommended dose of 1000 f-Lg/m2 in dogs) demonstrated I ,II" " II'd II' Ii 0 1 in uterine blood flow, with resultant fetal hypoxemia 111 ,1,"1.1,1/111, /1 '

II11 111'i1 111 "dl'l lgs (kt'l:nl11in C', til tcl'rnine) are also not recommended I. I 1111 111"tll lll litlil 11111, ,1'1 ' 1111'11' 11 :11' i. dictntcd by the need to chemically

II I II 11 11 , ti l 11111 ,11 IH ,elll 'l ' 11'1111 h.' I\,lIldl. ," ,

326 PASCOE & MOON

Local Anesthetic Techniques

In people, the maternal mortality rate is 17 times lower when local anesthetic techniques are used compared with general anesthesia.38

These techniques are also chosen to minimize fetal depression because they decrease the amount of drug that is absorbed by the fetus. In women, it seems that epidural techniques produce less neonatal depression compared with general anesthesia,so, 83 but potential adverse effects such as severe hypotension continue to remind us that no technique is perfectly safe.9 It is possible to perform the cesarean section with a local infiltrative line block (up to 2 mg/kg of lidocaine diluted to the volume necessary to infiltrate the incision site) until the puppies or kittens have been delivered. Inhalant anesthesia can then be provided if needed during closure of the uterus and abdominal wall.

Epidural lidocaine (2-3 mg/kg, not to exceed a maximum volume of 6 mL) may be used, and the uptake of the drug can be reduced by the addition of epinephrine (5 J-Lg/mL). The epinephrine also intensifies and prolongs the block achieved with the lidocaine. In cats, and occasionally in dogs, the needle penetrates the dura mater, and cerebrospinal fluid is obtained. At this point, the clinician can try to replace the needle in the epidural space or can inject 25% of the calculated epidural dose into the subarachnoid space. Lidocaine is preferable to bupivacaine, because bupivacaine has too long a duration of action (3-4 hours) and is 20 times more potent as a negative inotrope should the local anesthetic be absorbed systemically. Less local anesthetic is required with epidurals performed during pregnancy because of the distention of the epidural veins from increased collateral blood flow. This venous distention decreases the epidural and cerebrospinal fluid spaces and facilitates transfer of drugs into the cerebrospinal fluid. Care must be taken to remain on midline and to keep the tip of the needle as close to the ligamentum flavum as possible (i.e., do not push the needle to the floor of the spinal canal) when performing these blocks, because inadvertent entry into the epidural veins is more likely. Hypotension secondary to sympathetic blockade may occur, and higher blocks may depress respiration or induce respiratory arrest. The hypotension has been shown to occur despite preoperative fluid loading in women, and uterine blood flow may be decreased even with normal systemic maternal blood pressures .'16 Hypotension did not occur in healthy bitches given 3 mg/kg of lidocaine epidurally,64 although it certainly can occur clinically; thus, it is st ill important to monitor blood pressure in these patients. The benefits of ,local anesthetic techniques must be weighed against the increas d tin (' required to perform them and the quantity of d pr 'ss iv ' d ru gs I'hal IlHl need to be given to the dam 0 as to po ition hel' tl il el do the HlII')\t'I" . Alternatively, any local b locl r nn bt' )~iv" 11 l '() Il I 'III' I'{'nti y wi lh 1',('IH' I' 11 1 anesthesia such thLlt Ll Ii ' hi pin I1\' Ilf' )',v lI! '!'ill 1I1 1I 'H I IH'tl l.l i l IUll lll lli ril" I'I·1I o tha t 1"11(' I nti en l iH t ll ) " lI l )/ w inll l 11\ 11 .r ll , II )',I' ,III I I I lI 'llvldl,d I ,y 11 11 ' 11\(',d

i:('l'hlliql i1 '.


General Anesthesia

As indicated previously, a rapid induction technique is desirable after preoxygenation because of the increased potential for regurgitation and aspiration during induction of the pregnant patient. As previously discussed, any delay in intubation or protection of the airway should be avoided; thus, anesthetic protocols with long induction times such as those administered by mask or IV opioid induction may not be appropriate. Even when concern for aspiration is low, one author (PFM) avoids mask induction techniques because of inhalant gas exposure to personnel and prefers a rapid IV technique for all cesarean sections. The other author (PJP) advocates the use of mask induction with an inhalant, because it is likely to have the least effect on the puppies or kittens (the inhalant is breathed off rapidly and does not need to be metabolized) and is a simple technique that is familiar to most clinicians. It is accepted that there may be a risk of aspiration pneumonia, but the data collected so far do not pinpoint the time of aspiration in the bitch. For an injectable technique, the authors' preference is propofol-isoflurane in uncompromised cesarean sections, with or without opioid premedication. In critically depressed dams, a small IV dose of fentanyl is used before induction with etomidate, followed by isoflurane.

For cesarean section, puppies may do better if propofol or isoflurane is used in the anesthetic protocol,31 Propofol and thiobarbiturates (thiopentallthiamylal) have been used in human obstetric medicine, and both have the advantage of rapid onset and short duration with minimal residual fetal depression. 60, 88, 89 Neither drug should be used without consideration of the dam's clinical condition. Both have significant cardiopulmonary effects and need to be titrated carefully to effect. Bradyarrhythmias (with propofol) and ventricular and supraventricular arrhythmias (with barbiturates)48 may occur as well as decreases in myocardial contractility and preload. These effects decrease cardiac output, blood pressure, and, most importantly, uterine blood flow. Propofol and the barbiturates cause a transient apnea and may cause severe fetal hypoxia n nd acidemia if the mother is not preoxygenated, rapidly intubated, and provided with enriched oxygen with assisted ventilation. These transient l' ff cts may not be problematic in healthy patients but enhance fetal ,) ' idosis and hypoxia if these conditions are preexistent. Although proporol 'i generally safe as an induction agent, maintenance of anesthesia with propofol is not yet recommended, as initial investigations in infants Ind i ate low er neurologic and adaptive capacity scores compared with Ilm, (' ottain d Lls.ing thi pental.96 Safety with the barbiturates can be IIH 'i'l'f1 HCd if the nfl' lIdlllini t:J t 'r d with either lidocaine (0.25-1.0 mg/kg IV) ()\' dl :Ii',cpnl1l (0, I ()" mg/ I g 'IV), both of which reduce the induction dlll I' l'('qu in" 1, I ) ) 't ,( ' p ,llI ) !"IVI 'I I 10 the moth r h as b n shown to alter 11 11'1'1I11l1" ')\ lil lI l (l ll 1III II IIII I'lll ,II !J I,. /1, 1,,,,111 bliino lata on thi fj a r' avaHabl III dl'I',r III' , ' fl i M" ll llI ll ,' l id II lll y dHIJ h( , tlHt'd ill IIbHh'II'I I' IlIll'H lhcHin, il IIIIIII )'," 1111' dll I" 11I', ·d l,rllli rill) ', I 01111 11 ' II I Iii III (·1 III 1I ',l d I" ~ ' H1H ' r"t rI

.1 "111 '" I 1'"1 II

328 PASCOE & MOON

Ketamine (4-6 mg/kg N) combined with diazepam (0.2-0.4 mg/kg N) or midazolam (0.1-0.3 mg/kg N) is an alternative rapid induction technique with positive cardiovascular effects and may be considered in critically ill dams. In women, ketamine provided better cardiovascular effects than thiopental, although neither choice affected the general condition of the neonate.48 Thiopental inductions caused a transient decrease in uterine blood flow, although ketamine did not.48 In addition, ketamine administered IV at 5 mg/kg was shown to maintain or increase blood pressure and to increase uterine blood flow by 15% in nearterm ewes.S1 Ketamine combinations did not affect puppy survival. 59 A residual depressant effect has been observed in puppies,s9 human babies,2s and primates28 after cesarean section, necessitating intensive neonatal resuscitation. Thus, it seems that ketamine causes fewer cardiovascular disturbances in the dam and fetus than propofol or thiopental but may have more prolonged depressant effects on the fetus. Diazepam and midazolam can be reversed with flumazenil (0.1 mg/kg) if necessary, but these drugs rarely alter cardiovascular function if less than 0.5 mg/kg administered IV is used. Some puppies may seem to have poor muscle tone after administration of benzodiazepines, and this may be a good indication for flumazenil reversal.

In severely ill dams, etomidate (1-2 mg/kg IV) is a safe but expensive induction agent. Advantages of etomidate include excellent cardiovascular support, rapid onset, and short duration of action. There was no difference in Apgar scores (scores that measure baby vigor after delivery) when etomidate was compared with methohexitaVO and etomidate had more favorable fetal acid- base measurements compared with thiopentaF6,43 for human cesarean section. As is the case in the adult, transient cortisol suppression occurs in the fetus when there is maternal administration of etomidate.20 Without premedication, etomidate may cause some gagging or retching, but induction is rapid and aspiration is unlikely if the airway can be secured quickly. .

Opioid induction can be used in dogs but not in cats. Ideally, drugs with rapid onset and short duration should be used. In this context fentanyl, alfentanil, and remifentanil would be superior to oxymorphone or methadone. Advantages with opioid use are their excellent maternal analgesia and minimal cardiovascular effects. Disadvantages are maternal respiratory depression (necessitating assisted ventilation), the concurrent use of benzodiazepines, and bradycardia, which can be treated with anticholinergics. If bradycardia occurs, atropine (0.02-0.04 l11 g /kg) is the anticholinergic of choice, because glycopyrrolate doe no t r OSi:J

the placental barrier and the bradycardia m ay be occurring .in the f lus as well. Oxymorphone has great r depr s an t a tivi ty in hllm l1n IWO~ nates than the other opioids. Fentany l, on \'\" o \'l ll'f' h:IIHI , CillI HCd no change in neonatal Apg, f' S o rcs, I lood gd, p" ()I' lIl ('I'ilH' hl ood flo w, suggesting it sa fe l (01' il1ll'<I0lwl'f1 li vl' .111.1I)',I'II i. 1 (~ \ III p,)',/ I /,. IV) , I\i sLIming, Pllic:tli o ll (I1 1111111olll d.llil 1(1 1IIl ' dll )'" 1I 'IILill ylll iol Y 111l11I1 'I' Il'rn PIlPI <I ('p\'( ', r i(l/l IIt,," II VlI lt lll"IlIl Il ' ( ',111\" 1 ,1,1\,, 111 1111 .1 " 11C' 111 )',1 111 1' Ijlilil ' 11'1\1 liv i' III II" , 1' 11 1',1 , III " I Jillitl 111111 11111"" \\'11 11 1,1 11"1 ' q'I ' III .tl, ~ 11


and it is unclear if veterinarians should be equally concerned over opioid depression in the dog. In general, opioids were not a risk factor during cesarean section in the dog,59 and depression may be reversed with naloxone (1-10 J.Lg/kg IV or intramuscularly).

Although all inhalant anesthetics have been used successfully for canine cesarean section, methoxyflurane was associated with decreased puppy survival,59 Halothane did not have any positive or negative effect on cesarean section- derived puppies, and isoflurane was associated with improved neonatal survival,5, 98 In healthy women, neonates were also unaffected by halothane as long as the induction-delivery interval was short, but when fetal distress was present, halothane aggravated the fetal condition.72 Halothane is thus not recommended for emergency surgery. Nitrous oxide, a less potent inhalant anesthetic, is sometimes used to supplement anesthesia. Because nitrous oxide decreases the oxygen delivery of the mother, it is not recommended in any situation where maternal hypoventilation or hypoxia may occur. Nitrous oxide reaches equilibrium with the fetus within 20 minutes, and if the anesthesia is prolonged, nitrous oxide has been associated with infant depression.62 Furthermore, diffusion hypoxia in the neonate may occur after delivery. Nitrous oxide is used extensively for cesarean sections in women, but times from induction to delivery are often shorter in people; thus, care should be taken with its use in dogs and cats. Although there () re currently no data on cesarean section using sevoflurane or desflurane in cats and dogs, it is expected that the use of these drugs would be rlssociated with even faster recoveries than with isoflurane.

Competitive neuromuscular blocking drugs such as atracurium are large polar molecules that do not cross the placental barrier to any l'xtent. The addition of a neuromuscular blocking drug may allow one louse less anesthetic and hence decrease the degree of cardiovascular depression. The addition of atracurium during cesarean section necessil(ltes the use of intermittent positive-pressure ventilation, and care should be taken not to hyperventilate the animal.

In dogs, if the dam is "lethargic" after surgery, litter survival de-1'1' ases,59 and this may be an area on which to focus future studies. I. ,thargy may be influenced not only by the condition of the dam before SlIf'g ry but by other factors such as duration of surgery and type of ,111 " thetic teclu1ique. Although it is rarely reported, ketotic hyperglyceIllin ha occurred in canine pregnancies and may contribute to poor lil[lt'rna l status. Dam depression probably also results in poor care of lilt' I III p i 's by the mother during the critical postoperative period. Nlllrili o l1 a l "Ind suppo rtive needs of the puppies (e.g., being dried, lilll lil ull'd , WDf'm(.' I) sho uld be carefully attended to by the care pro

viii, '!' ill illl :ILiol1s w he re "he dam do - n t em to be recovering 1IIII'Ill ,III y 11'(1111 lilt' Hil f')\ic:ll procedure. Immed iate ass ssm nt o f the dam 11111 I i "d il',il t' 11\1' 1)('I'1i (01' ,'nnlil1l1 t'd cnl'( liovnl'{('I rI <l f' Stlpj1of'I , o X W'n

111'\111 '1111 '111 11 111 11 , II WII I'IlI"I ' (' ll v im" III ('"I , dlHI ,ll ld ili()I1,tI l'I'i lk. lI ( '1 11'('

III 111 /1)'," 1111 ',,1 I"" lil lli " ' 11111\ it! II I 1111 ' 111/'111/1 1I11t! 11,11111' 11 111 11 '1'1'111" 1" "'11 til '

330 PASCOE & MOON

scribed with the stated advantage that this is a safe and effective alternative to cesarean section (assuming the need for ovariohysterectomy).82 In the article describing the technique, the maximum time from clamping the vessels to removal of the uterus was 60 seconds, but in less experienced hands, it may take a lot longer than this. In an elective cesarean section, a clamp time of several minutes may not affect neonatal survival, but in an emergency, where the fetuses may already be severely stressed, the use of this technique may adversely affect neonatal survival.

ANESTHESIA OF THE NEONATE

Neonatal Pharmacology

The distribution and metabolism of drugs are different in the neonate than in the adult. Some of the factors involved are as follows:

1. Decreased protein binding. This is a result o£', generally lower albumin levels, and the albumin present also has a lower affinity for drugs. Neonates also have decreased a 1-acid glycoprotein concentrations, which are important for some drugs (e.g., lidocaine, alfentanil, sufentanil). In people, alfentanil varied between being 81% and 92% protein bound in the mother versus between 58% and 74% in newborn children. The differences were directly correlated with the acacid glycoprotein concentrations.55

2. Increased permeability of the blood- brain barrier. The bloodbrain barrier is five to six times more permeable to pentobarbital and morphine in neonates than it is in adults.

3. Neonates have higher body water content and lower fat content than adults. This results in a greater initial volume of distribution for some drugs. More lipid-soluble drugs should have a smaller average volume of distribution, and this seems to be the case with fentanyl, sufentanil, and alfentanil. Lidocaine and mepivacaine, which are also highly lipid soluble, show increased volumes of distribution, and it has been speculated that a greater proportion of the blood flow goes to the vessel-rich group of tissues, hence increasing the volume of distribution. Other factors such as pulmonary uptake of local anesthetics and protein binding may al 0 playa role in this finding.

4. In most neonatal animals, there is a decreased ability to metabolize drugs. Phase 1 reactions are those that oxidiz , hyd rolyz , or reduce a drug. The cytochrome P450 and NAI I II :,;ys l: ' 111 :4 nl'l' not well developed in th n onat -; thll S, dru gs rVlJlliril1g Ihvsv phase 1 reactions a r nwl'at 1)li Z,t' d mOrt' /'.dl)wl , ( )I)(' 11 H'Il HlIl'l' Il l' cytochrome P450 ndi vil ill PIIPI i('. ilHI WI,d d Id>do ld i l \l' I'( '. I ~I I ' over the fil's l tl WI I,'I (11 iii " , wilir II IIIIII'II IIt! 11 1'11'1 1 I' II IIVi ll )I, o CllITVd h IJ wl'I,I, I Iii 11)',1 ' ( h ,,1.1I 11I1 I, II I! ' 11 111/ I ,'lI i,I" 111 prOI'I'1I II I Irl lllIl 1IIId II,,' """'i' Iy ,11 ' 111 1 1111 11 '111 1' I 'I lil il y Irll"1


birth. Phase 2 reactions are the conjugation reactions, and these are poorly developed at birth (one third- one fourth of adult activity in dogs). These immature processes affect the duration of effect of some anesthetic agents (e.g., pentobarbital in 1-dayold rabbits administered intraperitoneally (IP) at a rate of 18 mg/ kg produces a sleep time of 173-265 minutes versus 12- 27 minutes in the adult,93 and ketamine administered IP at a rate of 75 mg/kg causes a sleep time of 95 minutes in rats less than 1 week old versus = 30 minutes in 16-week-old rats91). Although there are few data available on the neonates of our domestic animals, the clinical response to some drugs requiring hepatic metabolism indicates that these neonates are likely to have a decreased ability to detoxify drugs. Glycogen stores in the newborn animal are relatively low, and although glucose levels are well maintained in normal and normal fasted neonates, these neonates may become hypoglycemic if stressed and fasted. Renal clearance rates are slower in the neonatal animal than they are in the adult. Nephrogenesis in puppies is not complete until the third week of life, and the outer cortical nephrons are the last ones to become fully functional. The ability of the neonatal kidney to produce concentrated urine is less than that of the adult; thus, fluid balance is more labile in neonates.

5. The differences in neonatal respiratory function mean that inhaled agents have a more rapid onset and recovery (higher ratio of alveolar ventilation to FRC, increased permeability of the blood-brain barrier, increased flow to the vessel-rich group of organs, decreased body fat stores).l1 In contrast, the upper airway of puppies seems to be more reactive to the presence of inhalants, and this may decrease their minute ventilation and rate of uptake of the drug.86

6. Altered minimum alveolar concentration of inhalants at which 50% of the subjects do not respond to a noxious stimulus (MAC). In neonates, MAC is decreased but initially increases with age.36

The only data in small animals showed that the MAC of halothane in cats at 4 and 9 weeks and 2 years was 1.3% ± 0.01%, 1.39% ± 0.02, and 1.21%, respectively.65,66

7. Immature nervous system. Neonatal nerves require less local anesthetic to produce a block than adult nerves. Nerve conduction velocities are slower; thus, responses to some stimuli show Ion er latencies.4Q,87

8. Ill1rnatur neuromuscular junction, increasing muscle mass, and ch<lnging I11U S I fjb r types. These all have an impact on the dfl'CI of IWtll'() Il1U S Lil a I' jun tion bl ocking drugs. Succinylcholine :li'" Wf lill ll' Vl ll'i nl, ion ill dose reqlli rcm nt in th neonate comp,lI 'I'd W lit IIi( ' "dtrll Il H 11l1I )' (I , ' 11)(' do,'(' is h, sed on l11illi grc I11 S

111 ' 1 ' 111111 1' 11 11'11' 1' I ,I'll 1III '.r!'\lrillill i !'I ' I II Ii I'l l" 111 1111' IWIl I1 ;! I I '

111 1111 '" ,'d \ 11 1 11 11' ,111l1ll 111 1 l Id (III III 111 /" , 01 '"1 1'1, ,'/ 11 1"111 '1' 1111 ' 11'1 '

332 PASCOE & MOON

Preoperative Preparation

Animal

This must include a thorough physical examination, paying special attention to the cardiopulmonary system. Evaluation of the hematocrit and total protein are essential, and measurement of blood glucose is advisable. In the case of abdominal emergencies, the plasma/serum electrolytes are also essential guides to therapy. In neonates with a distended abdomen (e.g., intestinal accident, ruptured bladder), ventilation can be greatly improved if the abdomen is deflated. Deficits in circulating blood volume should be corrected using an appropriate solution (e.g., lactated Ringer's solution, Plasmalyte 148 (Travenol Laboratories, Deerfield, IL), Normosol R (CEVA Laboratories, Overland Park, KS), saline, blood [all with or without 2.5% to 5% dextrose]) . Because neonates have less tolerance to the stress of surgery and anesthesia, it is important that the preoperative preparation be optimal. Suckling animals do not need to be fasted preoperatively.

Equipment

The two biggest concerns with the anesthetic circuit are the resistance to breathing and the risk of increasing dead space. The largest source of resistance in these small creatures is usually the endotracheal tube because it is likely to have a much smaller diameter than the circuit to which it is attached. Standard endotracheal tubes can be obtained with a 2-mm internal diameter, but animals with smaller airways can be intubated using IV catheters. The relatively sharp and stiff ends of these catheters can be softened by the use of a small piece of silicone tubing glued to the end of the catheter.23 The use of these small endotracheal tubes is an indication for assisted or controlled ventilation. Sources of increased dead space would include endotracheal tubes that are too long and the space in the end of the circuit that is attached to the tube. Nonrebreathing circuits should normally be used because they have less resistance. A neonate's ability to breathe tends to fatigue more easily when an increased work of breathing is required; thus, intermittent positive-pressure ventilation is generally needed in neonatal puppies and kittens. This makes the choice of circuit less critical, because the work of breathing is being taken over by the anesthetist. Another argument against using a circle system is that the capacity of the yst In is large compared with the flows required with such small pati nts; c s a result, the rate of change of anesthetic con -ntration it> slow 'I'. Thi tl '; 111

bereducedtosomeextentby ui nga Innll rel r'<1l'hingbi1g:1I 11 pl·d i: d riL' rebreathing hoses or a p 'd iatri ircie H 1-' 1(' 111 .,

In human bcirl)"K/ l'I ll'r!' iI-I )'/!' 1I ! 'OIl('I 'I '11 (IVI' I' II Il' ('rrl 'I' IM (I I Id) ',11

con cnl nll' iOI1 H !)r () )';1' 11 i ll lil l' II1'P ll oI I I' 11( '1'111 1111' I I I II I!' plrl ' III I III I' I )l lI ) Ill'

r/'{innl d ~ 1 ) I II H j,1. iI(II ' 111 1111 '1 11i'(II 'I.d"I I" , til , ,, / 11 ' 11111111"11 111 Wi ll " " 11'1' 11 1

1(1 II I V(' 1111 1' l 'lil\ ( 'I t! 11I1I 111i '1 II I lIljl l ril ' 1111111 1· 111 1' 11


When dealing with any small patient, it is possible to overload the animal with fluids just because of the capacity of the fluid lines used for larger patients. In a 300-g patient with a flUid. r~te of 10 m~/kg/h (a total of 3 mL/h), it would be easy to exceed thIS Just by flushmg the IV line. For this reason, it is wise to use tubing with a much smaller internal diameter to avoid this problem. Care must also be taken to ensure that the lines do not contain any air, because these patients are quite small and may still have communication between the left and right atr~um, making it possible for IV air to produce coronary or cerebral embolI.

Premedication

In neonatal puppies and kittens, we usually do not use any premedication except for an anticholinergic (e.g., atropine or glycopyrrol.ate). As the animals get older, it is feasible to use almost any drug used m adult animals that is appropriate for the presenting clinical condition.

Induction Maintenance

For most neonates, a simple mask induction with an inhalant has given satisfactory results. Halothane, isoflurane, and sevoflura~e can. be used for this purpose. The addition of nitrous oxi~e may sp~ed mdu~tro~ slightly, and even in the patient in which its contmued use IS contramdIcated (e.g., severe intestinal distention), this brief use seems to be safe. Because the uptake of .ir:halants is sli.ghtly faster in ~he neona;;:~ ~~ neonates are more senSItive to the tOXIC effects of the Inhalants,' It IS usually unnecessary to turn the vaporizer beyond 3%. The larynx of neonatal kittens and puppies seems to be fragile, and great care sh~uld be taken to intubate atraumatically. In the extremely small young patient, careful consideration should be given to maintaining the animal with a mask so as to avoid the possibility of postoperative laryngeal edema. [nhalants also seem to cause a greater degree of cardiovascular depression in the neonate compared with the adult animal, which is probably the result of a negative inotropic effect and a blunting of the baroreceptor responses to hypotension.s. 92

•

Injectable drugs need to be metabolIzed, and because some of the I' quired enzyme systems are defi~ient ~t this age, the use of mo.st injec table drugs is not ideal. The thlObarbiturates can be. use~ safely m I itt 'ns and puppies over about 4 weeks of age. In pUppI:S, It has b~en HI own that the potency of the thiobarbiturates changes WIth ag~. Usmg " Iwnd I 1'01''' as an nd pOint, the median effective dose of IV thiopental W,\H Hhow n ('O in r 'as f ro m 1 lng/kg at J week of age to 4 mg/kg at 8 W('vkH or olgl' ," I CHpi l'!' 1'1)(' r<lel' that ancsth sia with a thi obarbitura~e W I '.H f o t'f h r( ld if'\ II'illllli ll ll , li lt' dl' \I )" h i l K IO() b(' metnbo li7.'d, and thIS p l'IH 'I'HH / p l'o l llll)',I'" ill 1\1 '(1 11011 rI ." d lll. rl ll, 'I' l l(', \' ,1 \1 l h o l'H wOlild ; lcl viK~' 11),"1 11 11 1 1111' II /It' II I III 1II I. I rillll ll l il , · I 111111 IIl ld ll I" II II Jl III 1"1.1 \ y l 1,1.1 ,

, '1'111 ' 111 11' ttl I I Ii HII ,II '" dill)', ( 1)1' 1111 11 Iii ' ,11111 li ll' l dl lll l ll') 11 11"(lIli li l il

illlillJl d l 11 III ,1111' ' III 111 ,d l ll ' l 11, '1" Ii 11,, /1 111 '1' 11 Jilil lV ll 11 1111 1111 1

334 PASCOE & MOON

elimination of ketamine is prolonged in the neonate. In neonatal rats «2 weeks old), IP ketamine was associated with a more rapid onset time «15 minutes versus 20-35 minutes for 10- to 6-week-old rats) and markedly prolonged sleeping times.91 In this study, it was also shown that the neonatal rats were able to metabolize ketamine to its first metabolite (norketamine) but that metabolite II was undetected until the rats were 3 weeks old. The production of metabolite II, which has a minimal anesthetic effect, requires oxidation, and it is known that this activity is deficient in neonates (even as adults, cats do not seem to metabolize ketamine beyond norketamine). Similar results concerning the pharmacokinetics of ketamine have been reported in human neonates. Ketamine may even be harmful in the first few days of life, because several NMDA antagonists have been associated with an increase in neuronal cell death in rat pUpS.44 These results suggest that the dissociative drugs should be avoided in the first 2 to 3 weeks of life.

Propofol can be used as an induction drug in young animals. It is a highly lipid-soluble drug, which initially redistributes to muscle and fat but is also rapidly metabolized by the liver. It induces cardiopulmonary depression similar to that induced by the thiobarbiturates. To date, there are no specific studies that have examined the effects or pharmacokinetics of propofol in puppies or kittens.

Etomidate could also be used, although the dose required is likely to be reduced.93 This drug preserves cardiovascular function better than most other anesthetics; thus, it may be useful for animals with significant cardiovascular compromise (including shock). As mentioned previously, it may suppress cortisol production, but this can be covered by the use of exogenous corticosteroids. The drug is hyperosmolar and may cause significant vascular reactions in neonates because of the small size of the vascular access and the fragile nature of the vessels.

Monitoring and Support

Because of the immaturity of the animal, it is especially important to support and monitor cardiopulmonary function. Unfortunately, we do not have the capability of obtaining the information necessary to understand the physiologic changes occurring under anesthesia; thus, we have to use our clinical skills and the imperfect monitoring tecbniques that we can apply to these small patients. As indicated pr viou Jy, cardiac output in these patients is dependent on rate; thus, pr ven ting

. bradycardia in a neonate is more important than in an adult. Monitors such as the esophageal stethoscope and the electrocardi ogram (II ,) are more useful in the neonate than in th adult, wh 'rc hea rl rate proviLi t'l-l little understanding of a rdiova. ul ar fU ll tiOIl . An Jo: ~C nl. () (I ll oWH Oil( '

to detect arrhythmi nH should lill 'Y 1l( 'I'UI' IIIHII 'r 11I lI'Hllw i.1. Wi th 111,1I1y o f these smoll rJ'(' ,1\I IJ"('H, il 1'+1 11 [II ' dlrnl 'ldl III )',1'1 ,I )"pod H( '( : 11 ' 11 '1' hl'(,IIII ,'I' or IIII' Hlll ,dl / 1'/1 ' II I Ill" 1':( '( : "111 1'1"" I ' 11111 1 1111 ' 11111 1" 1111 II I ),,1'1 11111', )',llIld 1'1111'111 '111111, I VI/,' 1111,1 111 ,11 1111 ' II " ,iI 1,1" , 111 11 '1\1 1'1'\1,11 1.


graphic electrodes with fine needles or pediatric ECG pads taped to the foot pads provides the best solution for overcoming this problem.

Because circulation is so labile in neonatal animals and resting blood pressures are normally low (see the article on neonatal critical care), it is helpful to be able to monitor blood pressure and support cardiovascular function. Doppler ultrasonography is a good monitor for indirect measurement of systolic blood pressure, although it can be difficult to get cuff sizes that are small enough for some newborn puppies and kittens. This technique is usually only reliable for the measurement of systolic pressure, but the clinician can make some judgment about the mean pressure by palpating the pulse and using pulse pressure as an indicator of the difference between systolic and diastolic pressure. Pulse pressures are often wide in the extremely young animal because of a patent ductus arteriosus (provides a low-resistance component to the systemic circulation). In many neonates, it is difficult to palpate the pulse because of their small size and increased coverage of subcutaneous fat. Direct p ressure monitoring should be used whenever possible in the sick neonate, but catheterization of the superficial arteries is not easy in these patients because of their small body size and the seeming fragility of their vessels.

Catheterization of superficial veins can also be difficult, although it is usually feasible. In the extremely young or small kitten or puppy, it may be easier to place a needle into the medullary cavity of a bone and give fluids through this access. The bones of these young patients are usually soft; thus, it is feasible to use a spinal needle or even a regular hypodermic needle. Fluids to be administered during the procedure should be warmed, and glucose (2.5%) can be added to the standard replacement solutions.

If hypotension is detected or it is judged that tissue perfusion is inadequate, treatment should be instituted. Initial therapy should in-lude a reduction in the amount of anesthetic if possible and an increase

in the rate of fluid administration. If these treatments are ineffective, it is probably better to use a positive inotrope or chronotrope than a peripheral vasoconstrictor to try to increase blood pressure (unless it is 'xtremely low and a vasoconstrictor is needed to raise the pressure long 'nough to allow other therapies to work). Dopamine has been shown to

iJ r ase blood pressure in puppies less than 10 days old at a rate of 5 Lo '10 f.Lg/kg/min but has little effect on heart rate or cardiac output. I )obutam in se m.s to have little effect at clinical doses. These experiIl .ents W ' I; arri d out in normal puppies, and the clinical response 1l1(i ~ ' dif r r nt in th hYI ot niv patient, but it certainly seems to be II" " I'hun in Ih l nd lill:. Adl'l'Ill',"!'i VdiO onstl'ictors may also be less " rrl'I 'li vI' lw(" lll. (. Ill' Ihl' iI1) 11I,1 11 1I' il or Ih ' ndren rgi r ptor in neonalid Ili ll'pil 'l il iid I II Ii ' 11 11, 111 H I,) 1,1 I" IY (l Id 11\)1'111;11 foa l,', a omparison III dllll1l1 ll1l1llll ' Wllh 111 111 ', ' 111'11111 1111' nlll lWI,t! Ilt lll Ih 'ilh (' I' dl'lI )', (',IIIHed f\

/ 1) ', lId 1'11111 I,ll' lil lllI l II 1111111 1 I'll ' 1111 ' 1'liI 111 ,11 "llblil"ll! 1)1' 111111111.11(1(\ 1111 IIIII "H I' III 1111111 ,). 1111 11" \ ' III 11111 ', 11 ,. III 111 '1111 I ii, ' III 1111 ' I d),,1 11'1 ' .I' ll " (I. 11111 1 III 11 )',1 1 )', 111 II) lilt ' 1)1111 I' :11 '1.111 III ' "li l/ h,d II 111 ',111 , I"

336 PASCOE & MOON

crease in heart rate and cardiac index (c. Craig, DVM, personal communication, 2000).

Core body temperature should be monitored, and hypothermia should be treated as soon as possible. A supplemental source of heat should be available (circulating water blanket or warm air blanket) to prevent hypothermia, because many of the anesthetic drugs eliminate the ability of the patient to thermoregulate, and neonatal animals are more prone to hypothermia than adults. It is particularly important to do everything possible to maintain normothermia in puppies and kittens because they cool down so easily. Hypothermia generally delays recovery because the decreased circulation and metabolism prolong the elimination of anesthetic drugs. The energy used to restore body temperature to normal may consume critical stores of glucose and predispose the puppy or kitten to hypoglycemia.

As indicated previously, neonatal animals are prone to hypoglycemia; thus, it is important to monitor blood glucose before, during, and after anesthesia. This can be difficult, because it is not always easy to obtain a blood sample from these young animals; thus, pretreatment with some dextrose and the inclusion of dextrose in the intraoperative fluids may help to prevent this.

Peri operative Analgesia

Although the nervous system of the neonate is immature, there is no doubt that nociceptive pathways are present and that pain is perceived by the neonate subjected to noxious stimuli. In some tests, the nociceptive threshold is much lower than it is in adults. This may be the result of a lack of some of the descending inhibitory mechanisms found in older animals. The coordination of motor responses to noxious stimuli is not well developed, and the animal may have much wider receptive fields to noxious events.42 Neurotransmitters may not have reached full function as evidenced by the lack of effect of NMDA antagonists in some nociceptive tests in neonates.l,S The W and K-opioid receptors are active but 8-receptor activation may be tied to weaning of the animal.9° These differences suggest that drugs effective in adults may not be as effective in neonates. Procedures carried out on neonates with insufficient pain control produce greater stress responses than those for whi 11 analgesia has been provided.94

,95 It is important to recognize potenti all y painful procedures and to treat accordingly. The pharmacokifl ti s o.f th opioid analgesics are different in the neonate and the adult. 1n hurn on babies, the elimination half-life of most opioid an alg si s is hi vhl' r 1'11:111

in adults.67 Recent studi s exarnining the (f('ets o( f 'I1I 01 I1 I .1IIt! 111!)1' phine in puppies have shown Ihol IOWN 'ti(I,'l'iol () ( Ilw t' dl 'II j\H ,In '

requir d for anll lgl's in nl I tid of d l\ ( ' ( '(llllPd)"( ,d wl lh ,II d ,lyl (I 111 '(1(' fourfo l I di(f<'I'(' l l<' ( 'H) .' " II ild l ,d /I (I hl '<' li IH IW /I 11,,11 ,,1I1 ' J1i< '11 ,11 '1' 111111 1' H,' m il iv)' 1(1 IIii' l'I't l dl 'l d Il IV 1\ "1 111' 11 1111 ,'11, " I II I 111111,,1111 11' . 111101 Ilt l/ w I II 'h 11 11 )',1 ',1 " 11 ' 111111 111" 1" IV ll lild I .. , 01 )', 11 . 111 '1 ,iI ,'I 1' 111 ' 11) ', 111 \ ,111 1 1111' 1111 '


of fentanyl as an analgesic in canine neonates.1O,53 Local anesthetics can be used and are quite effective. When using these drugs, the dose requirements are lower because of the immaturity of the nerves,4° but the neonate does not seem to be at any greater risk of toxic side effects with single doses of local anesthetics.61 There is little clinical information available on local anesthetic techniques for young cats and dogs.

Analgesia and anesthesia for tail docking and dewclaw removal in neonatal puppies have been subjects of debate for a long time. Given the current understanding of neonatal neuronal development, it is contrary to the oath that veterinarians take with regard to the prevention of suffering to carry out the procedure in the absence of any analgesic method. Application of local anesthetic techniques is difficult in small wiggling animals, however, and great care must be taken not to overdose the animal. The injection of a local anesthetic is invasive, carries some risk, and requires further handling of the animals with a time delay while the anesthetic takes effect. These factors make it hard to recommend the use of injectable local anesthetics. A topical application of eutectic mixture of local anesthetics (EMLA) cream has been shown to provide analgesia for circumcision in baby boys, but for this to work, adequate time is required for penetration into the skin (= 30 minutes), and the hair coat of the puppy would tend to resist the uptake of the drug. Systemic analgesics may be useful, but the doses of opioids and nonsteroidal anti-inflammatory drugs to use in these young patients have not been defined, and, as noted previously, ketamine may not be effective, because the NMDA receptors have not yet reached their adult pattern of distribution. More work needs to be done with respect to analgesia in neonatal puppies and kittens before sound recommendations can be made.

References

1. Abdul-Razzak R, Bagust J, Kerkut GA: Postnatal changes in the role of NMDA in the isolated spinal cord of the hamster, Mesocricetus auratus. Comp Biochem Physiol Pharmacol Toxicol Endocrinol 107:205-212, 1994

2. Abitbol MM: Inferior vena cava compression in the pregnant dog. Am J Obstet Gynecol 130:194-198, 1978

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r. HmO' (;1\ : M n lt ll'~ Li o ll of th biph~s i bchavioral and hear t rate response in the formalin 1('14 1. l' Io ,1 1'mol , 01 lIinch"11I Ik llll v 6():, 29- 33r., 1998

II, 11"11111'11 I): ('nl1i ,w d 14 1(1(' 1. 1 1\ 1'('v l,'w lI f Ihl' lil cra luO' . J ma ll Anim Prac t 15:101-11 '1, 1'1711

'1, IIt 'V ill1 I II{, 1II IId ,''' ' 11 1\ , I ,(I ii I" ,'1 11 1. ( '1\1/11'11', villi IIIII' III pO'('p,II,II' ey, 11M) '1:13- IEi, '1974 II , 111\ \l d " '" 11 II ', HI'I" 'Ii Il '1 1 1\ , ( ," >1 111\ ' 1I"" llid y" " " I, ' " II, ', 'lrl II I 11111,,11,"1\\ ' I" Ihl'

lI I'wl'lIl 11 Id)" I"1 I\ ,," ~ II, 1\ " ,ii I', /,1 ' II ' \" 1'1/11 'i 1111\, 1, ).' ( , i l' ,111 "" 1 "I IIIIII II II II " dll"" Io " III'( 11 11 ' " 1'/ \111 "III ,' 11 11 1 ~ ~ ,. , 1!l 1I1I '11 '1' 111 1"

\111 II '/I' 'II I 1'1'1 1

338 PASCOE & MOON

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37. !iaruta M, Funato T NII I II Y, ,'I ,Ii : 1.:1 111<'1 11 ii i IIl lill \1I111I !i YI"" 1'11111,,111 11 1111./ 'I Y ~\"" mhalatlon IlIl'in /\ lil(,o,' '"I 1,'lliI 1"1'"" H"II 11 1,,111 11 II " I'IIIIP'H' I N 1'1"111 ' 11 111 '1 1 11111,,1' 11

.nkkni ZI II lH lrl /l,I): I,ITI IIHI, 1'1/1/1


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:'6. Mo n '1, Erb H, Ludders I, e t a1: Perioperative management and mortality rates of dogs und rgoing cesa rean section in the United States and Canada. JAVMA 213:365-• (0,9 , 1991)

';7. M,)on 1' (1: An sl'h sin for ~n renn section in small animals. In. Proceedings from the N(l I'lh Anw ri ('nl1 Vctcl'innl' (lnrcrcl1', l'i and o, 1995, pp 21- 22

'iH, MO'"l ('11, S\'Il I'l " 1I 1M , I ,ild rl"I'H IW, vi ,I I: I,:rfl' 'l o f fentanyl on the minimum alveolar ,'II ll\'l 'llll',II I11 11 III i p ll llt', III1 ' III Hw l ,It ,. A'lI'::t li l'Nioln!;y W\:5:15 ·542, '1995

',Ii, MIII III I'P, l id, l iN , 1,llIlrl l' l'/ l IW, 1,1 " I: (" ' il lI l" 'I'IIII\II' l'iHk f.1C IOI'H for IIi PI i s deli vered hy l'I'lli l" ', I'1 111'1 '111111 I" IiII' I llti l"d ::111 11 '/' II lld ( ',II I'IIi" , I 1\ 111 1\ 111111 II 1Ifl P A H~()C :1(0,::159-\(,11, " 111111

1111 MI" Ii " I, 11111 I tvl 111\ 'iii 1,1 1 " I .iI I 'I' I'Ij "lil ll lI l' 11i 'II'\I "11i 1 111 1'1,"/111 11 1111 1"ll lllI' lil lI llI ' 111 1 1' 11 111 , 11,,11 ill ',1111 1111 <1 11 I, Iii, ,lil li ' II I' Id \ 11 11 ' 1 1 1 ,, ~ 1 1l II I1 11 II , jll l1"

340 PASCOE & MOON

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85. Sand er HW, l)1'r l1l11 I ~ M , ( ;I I1I ~ I"" II I' , ' :" 1\11 1 d Ylllll ldd il 1,, \ ,,11' 1'1 ," ',,1 I" II II' '"l ldl',I,,, 11I of prl' I', I1 I11 wy. HIli" 1'11 11 1'11 1111 " '\ 1'11\ '11' , '1111, I'IHII


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Peter J. Pascoe, BVSc Department of Surgical and Radiological Sciences

School of Veterinary Medicine University of California

Davis, CA 95616-8745


NEONATAL CRITICAL CARE

Paula F. Moon, DVM, Bruno J. Massat, DVM, and Peter J. Pascoe, BVSc

Between birth and the age of 2 to 3 weeks, puppies and kittens are defined as neonates. During this critical period of rapid growth, a delicate balance between oxygen consumption and delivery exists. Care of the diseased newborn must focus not only on treatment of the underlying disease but on aggressive supportive care.

NEONATAL PHYSIOLOGY

Vital Signs and Normal Blood Values

One important sign of health is adequate gain in body weight. For puppies, weight gain should be at a rate of 1 to 1.25 g/ d for each pound of anticipated adult weight. Puppies should double their weight by 10 to 12 days, and kittens should do the same by 14 days.z4

Blood pressure and body temperature are lower than those of adults, although heart rate and respiratory rate are higher (Table 1). As puppies and kittens mature, changes occur in the hemogram (Tables 2 and 3). Serum chemistry profiles show minimal variations from adult values (Tables 4 and 5).

Five minutes after birth, infant pH and blood gas values show a relative hypoxemia and acidemia (pH: 7.21 ± 0.05, Pacoz: 46 ± 7 mm Hg, base excess: - 8 ± 2 mmol/L, Paoz: 50 ± 10 mm Hg). At 1 hour after birth (pH: 7.33 ± 0.03, Pacoz: 36 ± 4 mm Hg, base excess: - 6 ± 1

Prom the S tion of Anesthesiology, College of Veterinary Medicine, Cornell University (PFM), And PI' iv~ t Practice (B1M), Ithaca, New York; and Department of Surgical and 'Radio llll\kll i .'d" I1\'('H, hool of Veterinary Medicine, University of California, Davis,

01 if(l l'll llI (I 'll ')

VI(T I(I{ INi\ I ' I I Ir 11 1 '1 111 hll li III i\ MI\I\lCA: SM A LL A N IMAL PR A T[ E

VI II Il tvlJ i I I • I II I ~ 1111 I I I I I , II '11111

344 MOON et al

Table 1. VITAL SIGNS IN NEONATAL AND PEDIATRIC DOGS'

Heart Rate Respiratory Systolic/Diastolic Mean Rate Mean Temperature (Mean)

Age (beats/min) (breaths/min) Range °c (OF) Blood Pressure (mm Hg)

0-24 hours 200-250t 15-35 34.4-36.0 (94-96.8) 54/ 30 (40):1: 1 week 220 36.1-37.2 (97-99) 2 weeks 212 36.4-37.1 (97.6- 98.8) 3 weeks 192 37.2-38.1 (99-100.5) 4 weeks 156--137§ 20-36 37.7 (100) 70/ 45 (60) 5 weeks 208 Adult 100-130 20- 24 38.5-39.5 (101- 102.5) 130/80 (100)~

' Unless otherwise indicated, data f rom Fox MW: Neonatal mortality in the dog. JAVMA 143:1219-1223,1963.

tData from Poffenbarger EM, Ralston SL, Chandler ML, et al: Canine neonatology. Part 1. Physio, logic differences between puppies and adults. Compend Contin Educ Pract Vet 12:1601- 1609, 1990.

:j:Data estimated from unpublished values from 30 near-term fetal lambs. Moon, PF: College of Veterinary Medicine, Cornell University, Ithaca, NY, 2000.

§Data from Magrini F: Haemodynamic determinants of the arterial blood pressure rise during growth in conscious puppies. Cardiovasc Res 12:422-428, 1978.

llData from Bodey AR, Michell AR: Epidemiological study of blood pressure in domestic dogs. J Small Anim Pract 37:116-125, 1996.

mmol/L, Pa02: 63 ± 11 mm Hg) and 1 day after birth (pH: 7.37 ± 0.03, Paco2: 33 ± 3 mm Hg, base excess: - 5 ± 1 mmol/L, Pao2: 73 ± 10 mm Hg), these values begin to normalize toward adult values.30

Cardiovascular

Initially, the systemic arterial pressure in the newborn is not much higher than in the mature fetus (see Table 1). Systemic vascular resistance, stroke volume, and arterial blood pressure all increase toward adult values over the first few weeks of life. Simultaneously, heart rate, cardiac output, plasma volume, and venous pressure all decrease. For a 4-week-old puppy, normal cardiac index is 0.22 ± 0.025 L/ kg/min (mean ± SEM), central venous pressure is 8 ± 2 mm Hg, and plasma volume is 0.068 ± 0.006 L/kg.36

An immature baroreceptor reflex and autonomic nervous system (particularly the sympathetic nervous system) prevent normal respon e to acute changes in blood pressure or to exogenous vasopressors or inotropes. Also, because of a high resting level of cardiac perform an c, the newborn has a limited capacity to respond to addition al tr 58 'S. Although an adult can increase its cardiac output by in r \cS ing hea rt rate or stroke volume (via preload), th mc h< nisms [I re , Ir(\(1 d 01-erating at peak p erfonnan in I'h \ new horn . Olll'ilig i'lw fin-II wI'('1 H of life, the newborn r s'l onti s In i11 ('r('fls i11 )', oXYI',(' 11 l'l'q ldn '111l'11i H h il 1('I'\ '1I 11

in g oxygen (' Irndioll I' llll l'l' 11 11 111 ('ill ,d illl ' 1II IIpl ii '1'111' III'wIHII 11' 0 11 11 '1' pril'l Hll' «( '( 'll liI- 1/1 II l'pil l/ II'i I" II I'111 II I "l ld lli ' 11 11 11 '" 1 III 11 'I Ij 'III II.(' III Il il lti 111'111 1' II VI'II " ll d ll, 11 11 ' 11 ' , II I,·d 111 11 1111111 I t! 1"l llId II II IY 1\1 1111 '

(f) (9 o o ....J

i:5 <I: Z o llJ Z

>I ~ « llJ I Z

(f) llJ :::> ....J

~ () (3 o ....J o ~ :2 llJ I LL o [jJ (9 z « a: o z «

11,1

346 MOON et al

Table 3. HEMATOLOGIC VALUES OF HEALTHY NEONATAL CATS

Hematologic Parameters

RBC ( x 106 JJ-L)* Hemoglobin (g/ dL) PCV (%)* MCV (fL)* MCH (pg)* MCHC (%)' Total WBC ( x 10'

JJ-L) Band neutrophils Segmented

neutrophils Lymphocytes Monocytes Eosinophils Basophils

0-21" 5.29 ± 0.24 12.1 ± 0.6 35.3 ± 1.7 67.4 ± 1.9 23.0 ± 0.6 34.5 ± 0.8 9.67 ± 0.57

0.06 ± 0.D2 5.96 ± 0.68

3.73 ± 0.52 0.01 ± 0.01 0.96 ± 0.43 0.02 ± 0.01

Age (in weeks)

2-4t 4.67 ± 0.10

8.7 ± 0.2 26.5 ± 0.8 53.9 ± 1.2 18.8 ± 0.8 33.0 ± 0.5

15.31 ± 1.21

0.11 ± 0.04 6.92 ± 0.77

6.56 ± 0.59 0.02 ± 0.02 1.40 ± 0.16

o

5.89 ± 0.23 9.6 ± 0.3

27.1 ± 0.8 45.6 ± 1.3 14.8 ± 0.6 31.9 ± 0.6

17.45 ± 1.37

0.20 ± 0.06 9.57 ± 1.65

6.41 ± 0.77 o

1.47 ± 0.25 o

6.57 ± 0.26 9.1 ± 0.3

29.8 ± 1.3 45.6 ± 1.0 13.9 ± 0.3 30.9 ± 0.5

18.07 ± 1.94

0.22 ± 0.08 6.75 ± 1.03

9.59 ± 1.57 0.01 ± 0.01 1.08 ± 0.20 0.p2 ± 0.02

Adult Range:j:

5.6-8.5 13.7-19.6

39-57 64-73 20- 27 31-37 7.5-19.9

o 3.9-14.7

1.5-5.2 0.3-2.2 0.1-1.6

0-0.1

Adapted from Bounous Dr, Hoskins JO, Boudreaux MK: The hematopoietic system. In Hoskins JO (ed): Veterinary Pediatrics. Philadelphia, WB Saunders, 1990, pp 294-295; with permission.

*MCHC = mean corpuscular hemoglobin concentration expressed as percentage; MCH = mean corpuscular hemoglobin expressed in picograms; MCV = mean corpuscular volume expressed in femoliters; NRBC/ lOO WBC = number of nucleated red blood cells per 100 white blood cells; PCV = packed cell volume expressed as percentage; RBC = red blood cells; total WBC = total number of white blood cells.

tOa/a from Meyers-Wallen VN, Haskins ME, Patterson OF: Hematologic values in healthy neonatal, weanling and juvenile kittens. Am J Vet Res 45:1322-1327, 1984.

iOata from Veterinary Medical Teaching Hospital, Clinical Pathology Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, 2000.

heart, brain, diaphragm, and adrenal glands and away from the spleen, gastrointestinal tract, skin, and kidneys. 31

Pulmonary

Initial respiratory rates are higher than adult levels, and tidal volume and minute ventilation are lower. The first inspiratory effort is singularly forceful to overcome resistance to lung expansion. In normal infants, this first breath can generate a mean negative pleural pr ssure of - 50 cm of water up to a maximum of - 100 cm of water:19

At birth, the newborn has only limited protection against hypoxia. One reason is that the fetal response to byp xia i th r vrsc r the adult one. Hypoxia causes a r ·du tion in f,tal r<'srirfltor I1'lOV('IlWI L and a lack of arousal. During the rirs l 4 10 tl,H hl)III'H () iI);C , 11I('r(' il-! Ii

transiti.on. from ('his r<'SPOIlS(' 1'0 (11(' 11111111 l'(' II PlllHI ' : ' 1\1 birlh, h 1'\».;1" an tr'iggt·!" 11'1(' (1'1'111 l'I'HPIlili I' IIHI lil li tll ·liI)' IIH ' IlIlI 1' 1 til I I Hi lll.lIl1 'ClIl II

I n'nlhill)l, . Th i: 11111,111 1' 11\ 1'( ' 11 1' 1'1111111'11" 1111'11/1 " "111 1111'1111" Ilillllll" li(lIl( ~; I ' I · (1\I.l , IlI'l 11111 11 11 IliI q' .1 II I', Ii"1 \ lid ill I," , 1II1 II f'" .1"11" ' 1'11'.1

(f) C) o o C) z => o >-~ (f) ill => ....J

~ ....J <l: ()

~ ill I () o m ....J <l: 2 a: o z u.. o W C) z <l: a: o z ::s

II)

V

II)

V

II)

V

II)

V

...... 00

...... 00 ...... ......

NOO 91 ...... ry,

8~ ...... \0 0"';

~cqo--!1 90) 8~ 0 ......

.,,;

G)~

91 ...... \0

SC C0 ry, o~

ON rir..r)

~J 8C II) ......

0"';

\117

348 MOON et al

Table 5. MEDIAN (AND RANGE) OF NORMAL BIOCHEMICAL VALUES IN YOUNG CATS

Age (in weeks)

Test 2 4-6 7-12 Adult Range

Albumin (g/dL)t 2.1 (2.0-2.4) 2.3 (2.2-2.4) 2.5- 3.0 ALP (IV/L)*t 123 (68- 269) 111 (90- 135) 10- 77 ALT (IV/L)*t 18 (11-24) 16 (14-26) AST (IV /L)*t 18 (8-48) 17 (12-24) 9-42 Bile acids* ND* <10 0-10 BSP % 30 min*t ND* ND* 0-3 Calcium (mg/dL) 9.7 (8.4-11.0) 9.9 (8.8-11.2):1: 7.8-11.3 Chloride (mEq/L) 122 (118-127) 122 (113-128):1: 112-129 Cholesterol (mg/ dL)t 229 (164-443) 361 (222-434) 150-270 Creatinine (mg/dL) 0.6 (0.5-0.7) 0.6 (0.4--1.0):1: 0.8-2.4 GGTP (IV /L)*t 1 (0- 3) 2 (0-3) 0-4 Glucose (mg/ dL)t 117 (76-129) 110 (99- 112) 63-144 Phosphorus (mg/dL) 7.4 (5.0-9.9) 8.2 (6.0-10.5):1: 3.1- 7.5 Potassium (mEq/L) 4.7 (3.7-5.6) 4.9 (3.6-7.1):1: 3.5-5.8 Sodium (mEq/L) 152 (147-158) 152 (144-160):1: 150-165 Total bilirubin (mg/dL)t 0.3 0.2 Total protein (g/dL)t 4.4 (4.0- 5.2) 4.8 (4.6- 5.2) 5.2 (4.2-6.7):1: 5.7-8.9

Adapted from Center SA, Hornbuckle WE, Hoskins JD: The liver and pancreas, p 206 and Crawford MA: The Urinary System, In Hoskins JD (ed): Veterinary Pediatrics: Dogs and Cats from Birth to Sex Months. Philadelphia, WB Saunders, 1990; p 274, with permission.

*ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BSP = bromosulfophthalein; GGTP = gamma-glutamyl transpeptidase; ND = not determined.

tData from Center SA, and Hornbuckle WE, College of Veterinary Medicine, Cornell University, Ithaca, NY, 1987.

:f:Data from Veterinary Medical Teaching Hospital, Clinical Pathology Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY, 2000.

functional reserve capacity, higher closing volume, and less resistance to muscle fatigue compared with adults. Increases in minute ventilation in response to hypoxia cannot be sustained in neonates. Instead, there is an initial brief increase in ventilation followed by a progressive decline; hence, treatment of neonatal hypoxia must be initiated before fatigue occurs. Finally, increases in environmental temperature reduce the ventilatory response to carbon dioxide, suggesting that too warm an environment may predispose newborns to respiratory failure .53 By the time they are 2 days of age, however, kittens respond to carbon dioxide nonnally.54

Renal

Micturition occurs within the firs t 24 h ()I II' s of Ijf(,. l):lil m il)(' output for 4- to 6-w d -old ki I t('ns is [j 11) 1,1 I 1\, wi I II .1 milll' () ~1I1l()1 Ii I I ,

of 1424 mOsl11/ 1 g. /\1 7 10 I WI'I,I II pi' Ii)',"', Ilwtll' 1:1111 '(1 )1( '1'111111 ' 'I' 1111 ./ 1 )'1 I1 IHI ,II. . Illnll lli / l )'" l'I 'I I" 'I' l lv l ·1y 'I'l li' 11.lldl 1'1 11 11 11 1 II 11.1 Iy 11 1'111\ '

(llil)lId I ii 10 III ' 1() 1111 ./ 11)', I II 11i \ 111111"11 11 1111 )', ," dill y .1 , 11 '1 IIIlI "11 111

NEONATAL CRITICAL CARE 349

pletely mature until kittens and puppies are 8 weeks old, and glucosuria is frequently detected in neonatal puppies.13

Thermoregulation

Newborn puppies and kittens do not have the hypothalamic control necessary to maintain body temperature. Rectal temperatures fall rapidly during the first 30 minutes after birth.5 Newborns lose heat easily because of their high ratio of surface area to body mass, reduced subcutaneous fat stores, and poorly developed ability to shiver. In fact, until 6 days of age, they cannot shiver. In infants, nonshivering thermogenesis accounts for 40% of their total heat production. This occurs through catecholamine release and the breakdown of brown fat that is distributed over the neck, back, viscera, and great vessels.25 This mechanism has high energy requirements, and responding to hypothermia can cause an ill newborn to decompensate. The environmental temperature for which metabolism is minimal while normal body temperature is maintained is called the "neutral thermal temperature." Maintaining a neutral thermal environment minimizes oxygen demands and conserves energy.

POSTDELIVERY NEONATAL RESUSCITATION

Comparison with Infants

Of all newborn infants, about 5% require some supportive intervention. Most respond to simple resuscitative measures (Fig. I), and only 0.03% of deliveries require chest compressions.34 Assessment of infants at birth is done using an "Apgar" score to indicate "vigor." This score is based on five characteristics: heart rate, respiratory effort, muscle tone, reflex irritability, and color. A low score (1.7% of all live births) indicates an abnormality and is associated with infiJ.nt mortality. The risk of a low score is higher with low birth weight and severe malformations.46 Such a scoring system is not yet described for veterinary patients but, by analogy, the "runt" of the litter is the most likely to have postdelivery problems.

A veterinary study has shown that cesarean-derived puppies have a mortality of 8% at birth and 13% by 2 hours41 and that naturally delivered puppies have a mortality of 2.2% at birth and 8% by day 1.48

For the cesarean-derived puppies, the three most common methods of postdelivcry are were administration of a heat source (41%), doxapram (- 4%), ,nd () ),;('n (1.5%).41 Other therapy included administration of nolo Ill1\' (:n~, ), ,\ldici1o li n rgi.cs (2%), epinephrine (2%), glucose (1%), 1IIId "11.1'''"1111' '1\ 1 IlIlIhll li nn (,1°/.,). As Figure 1 indicates, these methods of ,'(1(1 11 111' 1111 1111 II I " <1 111"1'1'1111'1'0 111 I'he ones IS d in infant r suscitation. ( " 11111 '111 II 1111 \ II1 I 11 111 1111111 11 11 ( 'lI tlll IVl'pll 1" 1. ' ,' U)mcHIH I'h o l' vct:cr innritlns Ili ll' ldd I I, 111 11 1, IIII 1 , I 11 11111 ' 111 111111)'. III 11I"'V I'lll hypoll]l'l'IlIill II ld

350 MOON et al

Assess and Support:

Always Needed

Infrequently Needed

Temperature (warm and dry) Airway (position and suction) Breathing (stimulate to cry) Circulation (heart rate and color)

Dry, Warm, Position, Suction, Stimulate

Oxygen

Establish Effective Ventilation .Bag-valve mask .Endotracheal intubation

Chest Compressions

Figure 1. Inverted pyramid reflecting relative frequencies of neonatal resuscitation efforts for the newborn who does not have meconium-stained amniotic fluid, Note that a majority of newborns respond to simple measures. (From Shattuck KE: Neonatal resuscitation. In: Pediatric Advanced Life Support, The American Heart Association, 1997-99; with permission.)

hypoxia first and should reconsider the usefulness of some medications (see Fig. 1).

RECOMMENDATIONS FOR NEWBORN RESUSCITATION

The minimal equipment needed for neonatal resu itation is li s ted in Table 6,

Warming and Drying

Tht' 1'1 1'1 1 ( '(1 111 '( ' 111 II I'll ' , ' II! 1111 1.1 II VI,"II\"II1\ 111 II VI' IlIII"II II " II

1'1'1'1111\' 1111 ' /11' '1"1 ' " 1 111I ' lld ' l1 l l .1 1' 11 11 1111 1 1 11 1\11 II h l \ aI "1 11 ' 1 II' 11 \1' II ' I III IHII'

352 MOON et ai

to other resuscitative measures. The newborn can suffer rapid cooling and enormous heat loss initially via evaporation and then by radiation. Wet infants exposed to room air lost nearly five times more heat than those who were dried and warmed.16

Newborns should be dried immediately with prewarmed towels and placed under a radiant heater. Alternatively, a hair dryer set on "warm" and gently moved over the newborns provides a radiant heat source and still permits visualization and handling of the newborns. After resuscitation, newborns should remain in a warm environment if they cannot be returned to the dam immediately (i.e., cesarean section). An environmental temperature of 28.4°C to 32.2°C (85°F- 90°F) is recommended?' 47

Stimulation of Ventilation

The toweling and rubbing also provide tactile stimulation for spontaneous breathing. Clearing of nasal and oral passages should be done on all newborns. Puppies and kittens are often "swung" at this stage, with their heads down, to clear their mouth and nose of secretions. The head and neck of the animal must be fully supported in the hands to avoid injuries. A safer method for removing secretions is gentle application of controlled suction. An infant suction bulb (obtained in most drug stores) works well to aspirate fluid from the mouth and upper airway. In kittens and smaller puppies, a cotton-tipped swab may be all that is needed to clear fluid from the upper airway.

"Meconium aspiration syndrome" in the newborn is diagnosed by respiratory distress, thick meconium staining of oral and nasal secretions, and a chest radiograph with typical signs of aspiration. In infants, meconium staining alone is seen in approximately 14% of term pregnancies, and aspiration develops in only 0.2% of births. IS If there is evidence of thick meconium staining around the mouth but the newborn is spontaneously breathing, supplemental oxygen should be provided by face mask and the trachea should be suctioned with a soft catheter. IS If there is evidence of thick meconium staining during a cesarean section, tracheal suctioning can be attempted before the cord has been clamped and before the initiation of respiration. Great care is necessary to prevent trauma to the tracheal mucosa. Indeed, prolonged or overzealous suctioning can also cause a fall in arterial oxygen saturation. Deep suctioning may cause a vagally induced bradycardia or apnea. Suctioning should continue for no longer than 10 seconds, 100% oxygen should be supplied between suctioning, and heart rate should be con tinuo'usly monitored (a Doppler ultrasound probe placed on th ch.c t is a onv nient method).

Within the first 30 second of deliv t' ry (HS Ill(' inil ill l II I' illg ll nd suctioning are being carri d oul ), II v Iww lJl J1'11 ~d l o lild Ill' dH,'I'Hn'd fill' the presence o f sponl'll lw(J II H 11I"', lllJill /', ,11 11 1 .I "1'1 11'1111 '1 11 , !\ 11I 'I'III"il lF, n wborn wii"l [I 1'( ')', 111.11'1 11I '1I 1111 /" 1\1 '.1 11 ill II 11111 ' 11 1'1 I' I() III 11,1) ", 'III. pvr IlIintll ,' .lIlt! !lI lli, 11I 1\I 'tll 1I\I 'lld,I,IIi" 111 ,11 .1" 11 11 \1' l\I'wl lllll 1111/ II


normal heart rate but is apneic, tactile stimulation and oxygen administration by means of a face mask are usually effective to elicit respiration within 1 minute. If effective respiratory efforts do not begin or the heart rate begins to decrease, positive pressure should be applied by means of a face mask to expand the lungs. The head should be held in an extended position to minimize the amount of gas being forced into the stomach (in infants, gas does not enter the stomach when ventilating by face mask unless the inflation pressure exceeds 35 cm of water) ,49 The application of sufficient pressure to expand the lungs is difficult to achieve unless the face mask fits tightly. Although ventilation by means of a face mask may be useful in mildly depressed newborns, it is often unsuccessful in severely distressed newborns. If this approach does not give adequate chest expansion within two attempts, the newborn should be intubated and ventilated until it begins to breathe on its own.

Endotracheal intubation provides the greatest airway control and prevents gastric distention. It requires considerable skill when performed in newborns, because the tongue is large and not mobile, the airway is small, the tissues are fragile, and laryngospasm is possible. Ideally, the larynx should be visualized using a laryngoscope, and a tube should be gently passed into the trachea. In newborns with an airway too small to accommodate a 2-mm endotracheal tube, it is possible to use 12-, 14-, and 16-gauge intravenous catheters. To expand the lungs, start with an inflation pressure of approximately 20 cm of water and hold this initial breath for 2 to 3 seconds. Incremental increases in pressures up to 30 to 60 cm of water can be applied if initial attempts do not expand the lungs. Once lung expansion has been achieved, lower inspiratory pressures (10- 15 cm of water) and shorter inspiratory times (0.5- 1.0 second) are usually sufficient. Once the newborn begins to breathe spontaneously, the tube should be removed and oxygen supplied by face mask or chamber if needed.

Finally, some anecdotal success has been reported by stimulating the Jen Chung acupuncture point to initiate breathing when face mask ventilation and intubation attempts are unsuccessful. A 25-gauge needle is inserted into the nasal philtrum at the base of the nares. The needle is twisted when bone is contacted.

Cardiac Function

The 11 ed for prior ventilation must be emphasized, because cardiac ll1:Jssng i ' not likely to be effective in a hypoxic animal. Furthermore, Illl' most Ii i ' Iy atl s ' of newborn bradycardia or asystole is myocardial h po in. ( 11(\' v'nlil ll ii on hns be n tab lished, cardiac compressions IImllld lwg in if Illl' I)('W hOI"lI s lill h ; l ~ tI ~ I ()w, We'll I , or nbs nt heartbeat. III 11\l 111 l li n'vll ll, 1'11('11 1 ('OIl'l ll'I'H ill llH : luJlild Ill' ;Ippli l'd .1C rtlHS Ih t, Inte ral I'll" I wl dl , 11", '1 111111 ' Il l! ' 1'1 1,'/1 1 IH 1'111 ' '111,11 11 1' ll llI ll', 1! 11 1. 11 II I\' Vl'\I 'l' illol rili ll I lilt 11'1,1 Il l, ' hl'l lll '11 11 1 "1111 1111 ' 111 ,11 ' ,li d ill 1111111 '11' 1/1 111 11 1'1 III 'IIII I'ill )'. 11 1

11 11 11" 1111111 ,1. 111 ,,1"1 1 111"1 ,, 11 (") ', 1'11 1'.' hl 'lIlll 11111111(1)',1 ) 1"111 ,11 111111

354 MOON eta!

pression is more effective. A Doppler ultrasound flow probe held directly over the heart is often helpful in monitoring heart rates during this period. Epinephrine is used if no apex beat is auscultated or no pulse is felt. Naloxone should be administered only if the dam received intraoperative opioids before delivery (see section on resuscitation drugs for details on medications).

Route of Drug Administration

Gaining intravenous access in a newborn is difficult because of the small size and fragility of the vessels. The umbilical vein is the preferred site for vascular access during infant resuscitation. During a cesarean section, it is important to leave the umbilical cord long enough to allow venous access. The umbilical vein is the thin-walled, single, vascular structure, and the arteries are paired and thicker walled. The catheter should not be threaded more than 1 to 2 cm into the vein to avoid cannulation of a hepatic vessel. Failure to freely aspirate blood suggests that the catheter has been threaded too far into the vein. An umbilical artery may also be catheterized for fluid and drug administration, but intense vasoconstriction makes this vessel more difficult to cannulate. After catheterization, it is important to dilute the drug to a sufficient volume to reach the systemic circulation (because blood is no longer flowing in the vessel). Once resuscitation has been completed, the catheter should be removed to minimize the danger of infection or portal vein thrombosis.

Because the bones of newborns are soft, an intraosseous technique is easy to perform.45 A small needle (22-25 gauge) can be inserted into the proximal humerus (base of the greater tubercle), proximal femur (base of the greater trochanter), or proximomedial tibia. Studies in immature rabbits and piglets have evaluated the effects of different intraosseous solutions on the physes and growth rates of the infused bones. Changes observed in the physeal bone had completely resolved after 3 weeks, and no growth disturbances occurred, suggesting no long-term detrimental effects.4,55 Adverse results of intraosseous infusions include fractures, pulmonary emboli, and prolonged drug effects.56

Lipid-soluble drugs (atropine, epinephrine, lidocaine, and naloxone) may be given by the endotracheal route. The drugs should be dilut d first to increase the area of mucosal contact and improve uptake. Importantly, drug pharmacokinetics after endotracheal administration may be different between neonates and adults. For in tan e, on s tudy v a lLl ~ ating the usefulness of endotracheal atropin ' in hildr 'n on 'luLled thnl the onset of action was so d lay c1 t:h nl ii' p rt·cltld t .d LiNing II lroplll (' v ill this route for emerg ncy t lw rnp of IIf(1 lil n 'lI l l lollI !" il l'l l! I'nnli ll ,'" Spl' cific infol"lTla tion on 1·I'w (l fW (ldIH 'll1 (l l lid I'(l ili l ' o f III 'II ! ', ,1 dll) l l ti rll l'l tl loll in p UI plt'1'I 111111 1.,1 111 '1111 11 111'1 Il l ',


RESUSCITATION DRUGS

The drugs used in neonatal resuscitation are outlined in Table 7.

Atropine

In the newborn, bradycardia is synonymous with decreased cardiac output. ~he mecha~ism of bradycardia during hypoxia is from direct myoc~rdI~l dep-:esslOn rather than from a vagally mediated event; thus, atropme IS unhkely to be effective during hypoxia. Furthermore, if atropine does increase the heart rate, the resulting increase in myocardial ?xygen demand may be detrimental. Because of this concern, atropine IS no longer recommended for resuscitation of newborn infants.20,34 If the clinician is suspicious that the bradycardia is drug induced, attempts should be made to ~n~agonize ~he specific drug whenever feasible (e.g., nalo~one for an OpIOld ar:d ahpamezole or yohimbine for an alpha-2 agonIst) before symptomatIc treatment with an anticholinergic.

Doxapram

The use of this respiratory stimulant in canine neonatal resuscitation can be traced back to a brief article in which doxapram was administered ~o 22 puppie~ ? eliver.ed by cesarean section.26 Doxapram was injected mto .the umbIhcal vem at a rate of 1 to 2.5 mg, and all the puppies survIv~d. No contr?l group and no description of the degree of puppy hypOXIa were prOVIded; hence, the data are inconclusive. Doxapram is t~Ol~g~t to act as a centra~ s~imulant, and its effectiveness is profoundly chmmIshed when the bram IS already hypoxic.3 Given this information doxapram is unl~kely to be of much benefit in the apneic hypoxi~ newborn. Its routme use does not seem warranted, and it is not even mentioned in the literature concerning infant resuscitation. 20, 21, 34 Doxapram may be of us~ to increase ventilatory efforts once they have started, dlthough t~e duratI.on of action of the drug is relatively short (minutes). It can be gIVen by mtramuscular injection if venous access is not avail,1bJc, and this route may provide a longer duration of action.

Epinephrine

')'his i ~ Hti ll ,l'Iw dnlg o f hoi ~ for n on ataJ cardiac arrest, although 1'l lilirOV(' I'SIl'H ('XI. ' I :lhol ll dOH(', I'OU ll' ()( adlllinis tration, and side effects. ')'IIt , i l il l l.lI dOH(' I'm il) 111I1 1[1 IN In fI'!', / 1 g i ll lll l iIJiHI(' r(\ I intrav nously; 1111 '1'1'11 1 1111', dll/II,t! 1'1 11 1 III' )',1" "11 II 1'! ' j1! '1 11 1,d "dll l iIJi , Im l io l l i:-; 1){I('('HHill" , (lI l li' l' 11 11111111 '11 ' 11 )',/',1'1 1 1IIId 111 1' ,\I) tlll II I Iri l , (I I () ' 111 1'./ 1,1', I llil y , II'hi , lv !' II ii'

1" '1 1 II '/ I il i l ' 11/1 1 11 '1/ 11 11 1,,1 ,1 1111 11 11 \ I1I1 III,' 11i!',II!11 d lllll' Ii 111 '1111111, '11

II ,l.d, " III IIII' I'" 11" /11 "11 1 11 ' 1" II I II IJIII ' 1"II Ii ·, 1 '" III 1,, 1" 111 11 11111 11 111 '

z o ~ I-' (3 U) ::> U) w a: -l ;:; « z o w z z o w U) ::> U)

Cl ::> a: o r-: Q)

~

II I,

c o .c ~ Z Q)

II) o c S ~

U)

I I I I Nil) ('1) t.n OQrlNOOrlN oood6000

l1) l1) l1) l1) l1) Nl1)OO Nl1)OONl1)OONl1)OONl1)OO OO~N OOrlNOOrlNOOrlNOOrlN

L;

1 ~ .S

z 1

.~\~ " h


and the risk of inducing brain hemorrhage if such high blood pressures are maintained.9 Endotracheal administration of epinephrine can be done but may lead to intense vasoconstriction of the tracheal mucosa, resulting in poor drug uptake. If available, intravenous or intraosseous routes are preferred.

Glucose

Causes of hypoglycemia in the newborn are malnutrition during fetal development or an extremely stressful birth. Neonates with a low birth weight or those exposed to perinatal hypoxemia, sepsis, or toxemia of pregnancy are especially prone to hypoglycemia. Although many practitioners routinely give glucose to a newborn/8 this practice does not seem to be indicated2o. 34; the need for glucose administration is best assessed by measuring glucose concentrations. Tile empiric recommended dose of dextrose for hypoglycemic infants is a slow initial intravenous bolus of 2 to 4 mL/kg of a 10% solution (250-500 mg/kg),51 and this is an adequate dose in veterinary medicine as well. Oral glucose supplementation (2-3 mL/kg of a 10% dextrose solution) also may be necessary when the dam is recovering from cesarean surgery or when she is unwilling to nurse her offspring.

Naloxone

Research has now shown that naloxone is not particularly effective and may even be detrimental when used routinely in apneic newbornsY· 33 Its use was previously advocated based on the theory that an increase in fetal endorphin release during parturition was partially responsible for postdelivery respiratory depression. A recent study evaluated the effects of naloxone (administered directly to fetal sheep) on the fetal cardiovascular response to hypoxemia.33 The conclusion was that endorphins are necessary for the regulation of fetal circulation d uring hypoxemia but play no role in unstressed fetuses. Naloxone is thus useless in the normal fetus and undesirable in the stressed hypox' l11 lc fetus. Clinically, however, because placental drug passage may ontribute to the neonatal depression, naloxone may still be beneficial

in re piratory-compromised neonates when the dam has received an l' ogenou, op ioid as part of the anesthetic regimen. The current recomIlwndcd cl ost' in in fants i 0.1 rn. /k intramuscularly.21 This dose is 2.5 1I III l'S Ihe dmw l1()rrn nll y ITt'Ol11n end 'd for opioid reversal in adult dogs 11I 11 i. , Iill 1()w(' l' Ihil ll Ih l' () , 111 )', / 1 g l',ivvn to 98 infant with no adverse .,11" ,'''1,' ' 11\l 1', IV" 111l111 "II II Ii II 1111 '11 111,11 111 11 11(' IW e ('SHIH in s om puppies \'II Iii IIIw h,'l1 l1 1'11 1. ' Il l' 1'11.11 ' 1'i 1l 'liI ,II I( III . II IIH ' Ill'w ilo l'll IlI'C0i11 l 'R m o r 1II III IV('Il lti , " " ' 1[ ,,11 1111' III II II' II , il l l 1111" , 1111 /1 lil ll 'llIlI hi ' 11"'11\ ,,1\ w illi 11 111'1./ 111 ' II

358 MOON eta!

Oxygen

Since the reports of oxygen free radical production during reperfusion injury, there has been concern that providing oxygen during resuscitation is not indicated. Because few newborns are ever supplemented with oxygen for more than the first few minutes of life, the concern over this or other oxygen toxicity (e.g., retrolental fibroplasia and blindness) is minimal. Oxygen administration is beneficial during resuscitation to rapidly reverse the hypoxemia associated with birth.

Sodium Bicarbonate

No studies exist to demonstrate a beneficial effect of this drug in neonatal resuscitation. Acid- base therapy is still considered important in the treatment of severe neonatal acidosis or prolonged cardiac arrest provided that ventilation is supported. Sodium bicarbonate might be useful in the depressed acidemic puppy that is not responding to other supportive care. The recommended dose for presumptive acidosis is 1 to 2 mmol/kg intravenously.20, 34 Because the standard 8.4% preparation of sodium bicarbonate has an osmolality of 2000 mOsm/L, it should be diluted by adding 1 mL of bicarbonate to 5.7 mL of sterile water to provide an osmolality of 300 mOsm/ L. This decreases the risk of hypernatremia but increases the volume administered, with concern for possible volume overload. The drug should be given slowly, over at least 2 to 3 minutes in an arrest and over 30 to 60 minutes for treatment of nonarrest acidosis.

Tromethamine

Tromethamine (THAM; Abbott Laboratories, North Chicago, IL) does not produce the hyperosmolarity, hypernatremia, and hypercapnia of sodium bicarbonate43 and has been advocated as a safer buffer in the treatment of acidemic asphyxiated newborns.56 To restore the base deficit back to zero, the dose (in milliliters) for 0.3 M of tromethamine is the body weight in kilograms times the base deficit. Similar to bicarbonate, it should be administered slowly over 30 to 60 minutes.

ACUTELY ILL NEONATE AND SUPPORTIVE CARE

Canine neonatal mortality is 12% to 6%. 19, <1 0, 'IK Thl' n 1I ~(' of (k ;lI h is undetermined in most a s (28%). This n'in (Ol'q's I'l l(' Iw lid Ih" l (lil t' of the primary th rs pies sholl I I b~' nggrl'.·H ivI' 1111'1 Il l' liv l' ]'"n' , Til] ' nll lti l

commonl y d iogno/ol (ld Cil i i. I' or pllppy 11H l1'l ii i! In II I(' f 1'111 :'d I)l HII'1 iii Ir" Ulll il (111 %) 111'(' III / I<' II I tl ll']'('1 1111111' (, Ily II I] ' tlil ill ] lI ' 1l llf lfll '(J I'1 .Ii (· I ,]' ,

I]H 'III I])II , (11' 111'111 '1111 1' " I III\' wlll ,ll' 1\1', 1111 '11 \] , / h'l ]1111 1 11I 11/ I 11I 111I1I11 1d "


diagnosed cause is prematurity or immaturity (10%).19,48 Immature puppies die because they are too weak to suckle, neglected by the dam, or simply too underdeveloped to survive. These puppies must be identified immediately because they are more likely to survive if treated as orphaned.

Newborns are also likely to die if they rapidly lose weight, become hypothermic «34.4°C [94°FD, become bradycardic, or have periods of apnea after birth. Respiratory arrest generally precedes cardiac arrest in the newborn. Other signs of distress include muscle rigidity or flaccidity; gagging; fluid in the nostrils; or decreases in vocalization, locomotion, or righting reflex. Dehydration, hypothermia, and hypoglycemia, regardless of the causes, further compromise the fragile newborn, and correction of these abnormalities is a priority in patient care. For example, hypothermia can lead to decreased intestinal motil~ty and absorption of essential nutrients and can result in hypoglycemia. Monitoring is similar in the newborn and adult, although some equipment needs to be adapted for use in newborns.

Hypoglycemia

Neonates have normal serum glucose levels below the adult range. Blood glucose levels less than 35 to 40 mg/ dL in newborns or 40 to 50 mg/ dL between 2 weeks and 6 months of age are abnormal. Because of their limited glycogen stores and immature liver, newborns can become hypoglycemic within 2 to 3 hours of no food intakeY Even normal older puppies become hypoglycemic after 23 hours without feeding.40 A sick neonate that is unable to nurse is not only dehydrated but hypoglycemic. Predisposing factors for hypoglycemia include a debilitated or diabetic dam, low birth weight, prematurity, hypothermia, respiratory disease, bacteremia, or systemic inflammatory response syndrome. Clinical signs of hypoglycemia include incoordination, seizure, flaccidity, weakness, or coma. The severity of the signs does not always correlate with the degree of the hypoglycemia. Puppies with clinical hypoglycemia should be treated with a rapid intravenous infusion (2-4 mL/ kg over 1 minute) of 10% to 20% dextrose followed by a 2.5% to 10% dextrose infusion at 6 to 8 mg/kg/min.51 If there is no venous access, the solution can be given orally by gavage tube. If the hypoglycemia is recurrent or prolonged wi th no un derlying disease identified, problems with carbohydrate metubolism should be considered .

Hypovolomlfl flnd Dehydration

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360 MOON etal

maintenance fluid administration and not for acute volume replacement. Because of the absence of cardiac reserve capacity in the newborn, it is critical to maintain heart rates at age-determined normal levels and an adequate vascular volume (see Table 1) while avoiding fluid overload.

The rate of fluid administration is dependent on the severity of the fluid deficit. Hypovolemia or shock may require rates up to 40 to 45 mL/kg/h, but neonates must be monitored continuously during such a rapid rate of fluid administration. If the patient is normovolemic but dehydrated, fluid replacement should be administered over a 6- to 8-hour period, and maintenance fluids (40-50 mL/kg/ d) can be given over 24 hours. Circulatory overload can cause a number of life-threatening problems in the newborn (bronchopulmonary dysplasia, persistent patent ductus arteriosus, intracranial hemorrhage, and necrotizing colitis).24 Signs of overhydration include serous nasal discharge, tachypnea, dyspnea, polyuria, chemosis, restlessness, vomiting, diarrhea, ascites, and pulmonary edema. Cardiac slowing in response to increases in blood pressure is not as marked, making monitoring of fluid administration based on heart rate response less reliable.52 Monitoring should include not only heart rate but respiratory rate and character, blood pressure, fluid balance (ins and outs), and general attitude.

Fluid type (crystalloid, colloid, or blood product) should be determined by replacing the fluid lost with a solution of similar composition.44

Specifically, newborns may be better able to metabolize buffers such as gluconate or acetate (Ringer's solution, Isolyte [McGraw, Irvine, CAl or Plasmalyte [Travenol Laboratories, Deerfield, ILl) instead of lactate (lactated Ringer's solution). Caution should be taken in administering crystalloid fluids with preservatives to kittens, as one report indicated severe adverse reactions (ataxia, seizures, coma) and death.14

Hypothermia

Normal neonatal body temperature is lower than that of adults, and attempting to maintain the adult value is not justified. Term babies have a neutral thermal range between 32°C and 34°C (89.6°F-93.2°F)? Thi value has not been established for animals. Maintaining an environmental temperature of 29.4°C to 32.2°C (85°F-90°F) and an air humidity between 55% and 65% until the neonate is 1 week of age and a temp rature of 26.7°C (80°F) from 1 to 2 weeks of age has been recommend ed .'17 A warmed container should be used whenever tran por tin n wborns. Radiant heat and warmed air maintain body t ·mp ratu l" ' b ·tt 'r thtl il circulating water mattresses.32 Fluid shou ld be wa 1"111(' I to J)o (9 ).8°11), and any inspired gas s (-.g., oxyg n) shou ld tl lso Iw Iwntc'<I 111 <1 hun1it! i fied.

Electrolyte Abnormlllltic

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transport across the placenta and an inadequate amount of parathyroid hormone. Contributing factors for hypocalcemia include septicemia, low birth weight, administration of sodium bicarbonate or citra ted blood products, and maternal diabetes.

RESPIRATORY EMERGENCIES

Differential diagnoses for respiratory difficulty in the neonate or pediatric patient include hydrothorax, congenital diaphragmatic or peritoneopericardial hernia, meconium aspiration syndrome, hyaline membrane disease, bacterial septicemia, pneumonia, iatrogenic pulmonary injury, or right-to-left congenital vascular shunts. Airway and respiratory problems are the leading cause of pediatric cardiac arrest, and this is probably true in veterinary pediatric medicine as well. Newborn brachiocephalic puppies have a higher risk of r;leath after delivery than other puppies.42 This also suggests that upper airway obstruction may be a silent killer in these animals.

Oxygen Therapy

Depending on the severity of the disease, oxygen therapy may range from 40% oxygen administered by face mask to 100% oxygen administered by intubation. Standard techniques of nasal insufflation are more difficult to implement in neonates because of their small nares. If appropriately sized tubing can be found, an oxygen flow rate of 50 mL/kg/min maintains a 97% hemoglobin saturation.37 Alternatively, the nasal cannula can be placed as close to the nares as possible without occluding the nasal passage, and the neonate can breathe the enriched air as it flows past the nostrils. Another method of oxygen supplementation can be provided by running the insufflation tube under a makeshift Elizabethan collar, with the collar's opening partially occluded with a I iece of plastic wrap. Part of the collar should be open to room air to prevent a buildup of carbon dioxide, heat, and humidity. Although fac tual information on the delivered oxygen percentage is unknown us ing thi method, the minimum useful flow rate is ~150 mL/kg/ min. Nasal insufflation and oxygen collars have the disadvantage of h. mp r in.g the neonate's mobility and ability to nurse; thus, their use l"i houl d b ' r 'Q rv ' d for p ati nts that are already immobile. They also hny ' th ' potenti,, 1 1:0 aus hYI ot]p 'I'mi a, because the delivered gases 11 1\' en id , I '/; I\' ill g Ih e IWO Il !iI !' i ll lin infa nt in ubator or oxygen cage is Illi ll 11I Il' 1) 1' 11)(1 h l 'H I 11 11' 1\)o d tl Ill' pl'l)YiLi ill i', on 'n!'i h d oxyg n environ-111\'111 , 11 1I 11'I,d , Il lI" 1111111 '111 1'. 111 11\1 1\1 . ' I',ll lly, II H I )', 114t ' '1111 b' wa rm d 11111 11111111 Ii I.'" 1\ 111 1d'l' d d ll (I V)', I' I I (' II)'," , II l lh (III )',11 II'HI (, t'lkli' 1l 1 I hil n n

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362 MOON et al

container of hot water in the cage (but out of reach) provides some humidity.

CARDIOVASCULAR EMERGENCIES

Hypovolemic Shock

Severe neonatal hypovolemia can occur at delivery as the result of a number of causes such as sequestration of blood in the placenta (during a cesarean section, when the newborn is held high above the uterus at the time of umbilical clamping), placental diseases, or rupture of the umbilical cord. The recommended treatment is administration of 10 to 25 mL/kg of fresh whole blood obtained aseptically from the placenta. Alternately, adult fresh whole blood, diluted packed red cells, or Oxyglobin (Biopure, Cambridge, MA) may be useful. If blood products are unavailable, colloids such as dextrans or hetastarch are also acceptable for rapid volume expansion.

In the neonate, sepsis develops primarily as a result of poor husbandry or newborn care. During the first 4 days of life, the umbilical cord is a likely source of infection. Maternal sepsis, metritis, or mastitis can also produce neonatal septic shock. Insufficient colostrum intake also favors infections.

Hemorrhagic Syndrome

In case of death of more than one neonate, spontaneous hemorrhag should be suspected. Indeed, newborns can easily become hypoprothrombinemic or deficient in vitamin K. Administration of vitamin K, (0.01-0.1 mg intramuscularly) in remaining littermates may prevent further deaths. Providing the dam with 5 mg of vitamin Kl daily during gestation may prevent this syndrome.40

Neonatal Isoerythrolysis

This syndrome is rare in puppies but can occur if th. dam rc civet! an incompatible blood transfusion befor Iv r prc rnan . i<ittC'nH wilh group A blood type can also d velop h rno ly l'i(" I 1l'111 i:1 i( I'll ' qll l'l'1l hll ~ naturally occurriDg group A a Il OZl nti bodi('s. '1'lw, I' Ill'wl \)I'n fll 'V I ll l ' l l

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MALNUTRITION

Malnutrition, although almost entirely treatable, is still a common cause of neonatal death in animals.19, 40, 48 Either maternal malnutrition or a small area of placental attachment can result in poor intrauterine growth, subsequent growth retardation, and postnatal weakness. Postnatal malnutrition can be caused by agalactia, mastitis, or lack of appropriate maternal behavior. Inappropriate nutrition can result in ineffective nursing, hypothermia, hypoglycemia, and death within 36 hours.40 Signs of malnourishment are lack of weight gain, poor or no attempt to nurse, constant high-pitched crying, inactivity, or a weak sucking reflex.

The caloric intake most often recommended for the healthy orphaned neonate is 60 calories per pound per day for the first w~ek, 70 calories per pound per day for the second week, 80 to 90 calones per pound per day for the third week and 100 calories per pound per day for the fourth week, assuming an environmental temperature of 29.4°C to 32.2°C (85°F-90°F).40

If the newborn is stressed or diseased, metabolic requirements are higher and proportional to the severity of the stress or illness. Monitoring for hypoglycemia and maintaining body temperature above 35°C (95°F) are necessary. If the patient is too weak to suckle or is hypothermic, a warmed 1:1 mixture of balanced crystalloid and 5% dextrose at 1 mL per 30 g of body weight may be injected subcutaneously, or a warmed (37.8°C [lOO°F]) nutrient-electrolyte solution may be administered orally every 15 to 30 minutes until the newborn responds.27 Oral feeding should not be done until the rectal temperature is above 35°C (95°F).

DIARRHEA

Overfeeding by well-meaning caregivers is a common cause of diarrhea in young orphaned neonates. Treatment consists of diluting the existing feeding formula in half with water or a balanced crystalloid 'olution. As the condition improves, the amount of milk replacer can

t; lowly be increased back to the normal levels. Other dietary causes of diarrhea in the newborn include a sudden change in the diet and food or lactose intolerance. There are numerous other causes of diarrhea (d ru g- induced, parasitic, infectious, obstructive, or metabolic diseases) fu r whi h mana gem. nt is discussed in greater detail in other reviews.28

COMPLICATIONS WITH THERAPY

bru~ Compllo "l'tlon

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364 MOON et al

rule of thumb, however, on how to adjust all drug doses. For example, in infants, acetaminophen's elimination may be twice the adult rate, but the elimination of bupivacaine may be prolonged up to 19 times the adult rate. 24 Consultation with a veterinary pharmacologist is necessary for drugs in which response to therapy is not easily evaluated.

A drug's osmolarity needs to be determined before administration to a neonate. Intracranial hemorrhage and necrotic enterocolitis can be caused by intravenous hypertonic fluid or drug administration. Intracranial hemorrhage can also be caused by acute hypervolemia, and necrotic enterocolitis can also occur after alimentary infusion of hypertonic solutions. Nutritional solutions, fluids, and drugs should not exceed an osmolarity of 460 mOsm/kg in the neonate.24

Hypovolemia from Blood Sampling

No more than 10% of the blood volume should be removed within a 24-hour period (a puppy's blood volume is 68 mL/kg'6). This volume should be replaced with fluids at a ratio of 3:1 if crystalloids are administered or at a ratio of 1:1 if colloids or blood products are being administered.46

Nosocomial Infections

The incidence of nosocomial infections in human pediatric units is between 6% and 14%. Babies who were more prone to develop infections were the ones who were immunocompromised, had received antibiotics that altered normal gut flora, or had received invasive procedures. The most common sites of infection were respiratory, urinary, gastrointestinal, blood stream, and surgical wounds. Not surprisingly, the single most significant method of prevention was simple hand washing between handling of patients.

Thermal Injury

Burns or overheating from heating pads, heat lamp , or hot wate r bottles can occur in the neonate that is depr ss d and unabl to mov '. Immediate therapy consists of applying o ld Or ic('d wat ·1' (~O '_ 17° . [37°P-63°PD to the burned site, aSf)('HH in l', () g<'nnti () I1 , .1I1d In'ilting (Ot' possible shock. Additional th l' l'rq ('() II I If{ 1111 l'I' pl (' Il IH ilill l; ollgolll )', llilid losses, treating th burn Hil t', 11I 'I'v \'111 II)', lil l·, 'IIIIII II, jll'l 'V(' IIIII1 )" II YI'()Ii1I 'I' mia, and provicl i Il l', I' ,liq 1'1,11'1 ~;II I, ' 11 1111 , .. 1 111, ·11 11 ',11 11111/ ,II ', ' ,.1 111 ' 1'1',1, silv I' Hli I (,,<I ill'/,II 1( ', 1\lld , ld' lI hi ' lli l i li' I


SUMMARY

The first few minutes after a neonate's birth may determine the quality of its entire life. Immediate care includes prevention of hypothermia, clearing of nasal and oral passages, stimulation of ventilation and oxygenation, and, in a few cases, advanced life support. Any addit~0r:-al stress during the first weeks of life can also result ill neonatal morbIdIty and mortality. Care of the diseased newborn must focus not only on treatment of the underlying disease but on aggressive supportive care. A safe, warm, clean, proper environment and adequate nutrition are essential.

References

1. American Heart Association: Textbook of Neonatal Resuscitation. American Heart Association, Dallas, TX, 1994

2. Antoon AY, Donovan MK: The Acutely III Child. In Behrman BE, Kliegman RM, Jenson HB (eds): Nelson Textbook of Pediatrics, ed 16. Philadelphia, WB Saunders, 2000, pp 287- 294

3. Bamford OS, Dawes GS, Hanson MA, et al: The effects of doxapram on breathing, heart rate and blood pressure in fetal lambs. Respir Physiol 66:387-396, 1986

4. Bielski RJ, Bassett GS, Fideler B, et al: Intraosseous infusions: Effects on the immature physis-an experimental model in rabbits. J Pediatr Orthop l3:511-515, 1993

5. Blanco CE: Peripheral control of breathing. In Hanson MA, Spencer JAD, Rodeck CH, et al (eds): Fetus and Neonate Physiology and Clinical Applications, vol 2. Breathmg. New York, Cambridge University Press, 1994

6. Bodey AR, Michell AR: Epidemiological study of blood pressure in domestic dogs. J Small Anim Pract 37:116--125,1996

7. Bonora M, Boule M: Breathing during sleep in fetus and newborn. In Hanson MA, Spencer JAD, Rodeck CH, et al (eds): Fetus and Neonate Physiology and Clinical Applications, vol 2. Breathing. New York, Cambridge University Press, 1994, pp 153-191

8. Bounous DI, Hoskins JD, Boudreaux MK: The hematopoietic system. In Hoskins JD (ed): Veterinary Pediatrics. Philadelphia, WB Saunders, 1990, pp 293-324 ..

9. Burchfield DJ, Berkowitz JD, Berg RA, et al: Medications in neonatal resuscItatIOn. Ann Emerg Med 22:435-439,1993 .

10. Center SA, Hornbuckle WE, Hoskins JD: The liver and pancreas. In Hoskins JD (ed): Veterinary Pediatrics. Philadelphia, WB Saunders, 1990, pp 205-248. .

11. Chas tain CB: Endocrine and metabolic systems. In Hoskms JD (ed): Vetermary PedIatrics. Philadelphia, WB Saunders, 1990, pp 249-269

'12. Chernick V, Manfreda J, De Booy VD, et al: Clinical trial of naloxone in birth asphyxia. J Ped iatr 113:519-525, 1988

13. rawford MA: The urinary system. In Hoskins JD (ed): Veterinary Pediatrics. Philadel-phi a, WI3 alll1der , ] 990, pp 271- 292 .

'111,. 1I11i H0 l1 HF, M 11 ::J "d PO, Bli k WB: Tox i.cosis in cats from the use of benzyl alcohol ill IOt' lnled Ring ' I" H Ho llil ioi1 . JAVMA '182:61, 198

I;;, (' IIIlIl I ,1 Iih ol lli AS, I " ' WI'IIl '1 HI ':, Mnrli" R), ' I' a l: Tl'a h al su.ction and meconium: A 1"'01'(1111''' HIII I" IIII'" II I t'IH"'. I 1'" lI IIII, ' 11 6: lii:1 11111., I ~90 . .

1, 1, 1),111111 1,:,/ 1111111 '/1 I ,H: N,'w llIl lIl 1"IIIP"" /l IIII '" " ," 1 "l1 tvll lnll'd Iw nl IIlKS 111 1'1, ' d 'livery 11111111 , 1',., 11 ,, 111 <1' d' l:' ,1 11 1>1 I, I 'I '/, I

1'/ 11,, 11 I/] !'v11'1 1' 1" ',''' 1\1 , WI I," III hU 'I'h,' 1" '11 1111111 11 1' . lI l d 111 11 1" II III II I'W 1," ill, · ,, 11111 1'1 \)11 1 111 '111,, 11 ,11 1111.1 I '1" 'l dllll \ 1" '111'.11 .1111 I " I, \" III '" I ' \ 111111 1,111" II}'/ \

III, iI, "" "III, 1'1 1 Mil 11111 11 01 11111" III I Ii 1111,11 ,11 1-'" 11111 1111111111 '\ 1'''" 111'1 11 I ,lIld ,' NI ' I 1111" -\, ,I,h 'lIll. 1'10 " 1'111 1 I'" II I 111'1

366 MOON et al

19. Fox MW: Neonatal mortality in the dog. JAVMA 143:1219- 1223, 1963 20. Frand MN, Honig KL, Hageman JR: Neonatal cardiopulmonary resuscitation: The

good news and the bad. Pediatr Clin North Am 45:587-598, 1998 21. Ginsberg HG, Goldsmith JP: Controversies in neonatal resuscitation. Clin Perinatol

25:1-15, 1998 22. Goetting MG, Paradis NA: High-dose epinephrine improves outcome from pediatric

cardiac arrest. Ann Emerg Med 20:22-26, 1991 23. Greco DS, Watters JW: The physical examination and radiology. In Hoskins JD (ed):

Veterinary Pediatrics. Philadelphia, WB Saunders, 1990, pp 1-18 24. Greene CE, Hoskins JD, Authement JM: Drug and blood component therapy. In

Hoskins JD (ed): Veterinary Pediatrics. Philadelphia, WB Saunders, 1990, pp 29--42 25. Himms-Hagen J: Thermogenesis in brown adipose tissue as an energy buffer, N Engl

J Med 311:1549-1558, 1984 26. Holladay JR: Routine use of doxapram hydrochloride in neonatal pups delivered by

cesarean section. Vet Med Small Anim Clin 66:28, 1971 27. Hoskins JD: The digestive system. In Veterinary Pediatrics. Philadelphia, WB Saunders,

1990, pp 139-193 28. Hoskins JD: Nutrition and nutritional disorders. In Veterinary Pediatrics. Philadelphia,

WB Saunders, 1990, pp 473--486 29. Jorgensen BG, Ostergaard D: Tracheal administration of atropine in children-effect

on heart rate. Paediatr Anaesth 7:461--463, 1997 30. Koch G, Wendel H: Adjustment of arterial blood gases and acid base balance in the

normal newborn infant during the first week of life. BioI Neonate 12:136-161, 1968 31. Koehler RC, Traystman RJ, Jones, Jr, MD: Regional blood flow and oxygen transport

during hypoxic and CO hypoxia in neonatal and adult sheep. Am J Physiol 248:H118-124,1985

32. Kurz A, Kurz M, Poeschl G, et al: Forced-air warming maintains intraoperative normothermia better than circulating-water mattresses. Anesth Analg 77:89- 95, 1993.

33. LaGamma EF, Itskovitz J, Rudolph AM: Effects of naloxone on fetal circulatory responses to hypoxemia. Am J Obstet Gynecol 143:933-940, 1982

34. Leuthner SR, Jansen RD, Hageman JR: Cardiopulmonary resuscitation of the newborn. Pediatr Clin North Am 41:893-907, 1994

35. Linder N, Aranada JV, Tsur M, et al: Need for endotracheal intubation and suction in meconium-stained neonates. J Pediatr 122:613-615, 1988

36. Magrini F: Haemodynamic determinants of the arterial blood pressure rise during growth in conscious puppies. Cardiovasc Res 12:422--428, 1978 .

37. Mann FA, Wagner-Mann C, Allert JA, et al: Comparison of intranasal and intratracheal oxygen administration in healthy awake dogs. Am J Vet Res 53:856-':860, 1992

38. Meyers-Wallen VN, Haskins ME, Patterson DF: Hematologic values in healthy neonatal, weaning and juvenile kittens. Am J Vet Res 45:1322-1327, 1984

39. Miller E: Diagnostic studies and sample collection in neonatal dogs and cats. Tn Bonagura JD (ed): Current Veterinary Therapy XII. Philadelphia, WB Saunders, 1995, pp 26-30

40. Moiser JE: Pediatric nutrition and diet. Comp Cont Ed Pract Vet 10:78-82, 1974 41. Moon PF: Fluid therapy and blood transfusion. In Seymour C, Gleed R (eds): Manual of

Small Animal Anesthesia and Analgesia. Cheltenham, British Small Animal Veterinary Association, 1999, pp 119-137

42. ¥oon PF, Gabor L, Gleed RD, et a1: Acid-base, metabolic and hemodynarni ff t~ oil sodium bicarbonate or tromethamine administration in anesthetized dogs w il'h experimentally induced metabolic acidosis. Am J Vet Res 58:771- 776, '1997

43. Moon PF, Erb HN, Ludders JW, et a1: A description of anin 'Ha rca n ~' li (H1 tl in i'lw United States and Canada. JAVMA 213:36 - 369, '1998

44. Moon PF, Erb HN, Lud I rA JW~ ,t a l: P' ri op 'r, li v(' "iHI fnt'l'o " ~ for 1'"1 1'1" :1 d"li vl" "'" by cesarean s clion in I'll<' l Jnil't'd SI'Il IW 111 \\.1 '11l1mlu, 1 1\ 11) 1\ ,11111 Il o,l!, I\nNI\!' :11>::1;;'1 368,2000

45. l'Co M, ('\'OWl' 1)'1 ', II" 1,11" 111 111111'11\ '11 "I'II II III'I I'll ill li 11'1'11111'1"1 '11 ' ill" 'lI 'IIII"\l II'"I I, III Ki,'" I{W, 1\(\ 11 111',1 11 '1 1 II I ("d 'l ) ( '111,,,"1 VI' II'rl ll lll y l'I" 'I'q 'y \ 1 11 111 1i11 1IIIII ,iI 1'1111 11". 1'lI lllI il l. ll'l lIlI , WII : '111111111 '1 I I'l'/" 1'1, 111'/ II '


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54. Wolsink JG, Berkenbosch A, DeGoede J, et al: Ventilatory sensitivities of peripheral and central chemoreceptors of young piglets to inhalation of CO2 in air. Pediatr Res 30:491--495, 1991

55. Woodall BN, Pender ES, Pollack CV, et al: Intraosseous infusion of resuscitative fluids and drugs: Long term effect on linear bone growth in pigs. South Med J 85:820-824, 1992

56. Zaritsky A: Pediatric resuscitation pharmacology. Ann Emerg Med 22:179-189, 1993


Paula F. Moon, DVM C3109 VMC

College of Veterinary Medicine Cornell University

Ithaca, NY 14853


CLINICAL THERIOGENOLOGY 0195-5616/ 01 $15.00 + .00

NEW CONCEPTS IN PEDIATRIC NUTRITION

Claudia A. Kirk, DVM, PhD

The goal of nutrition is to provide a diet optimal to meet an individual's specific physiologic needs at each life stage and to optimize performance. When feeding the puppy and kitten, we strive to supply the building blocks for optimal growth, health, and disease resistance. Qespite this understanding, the nutritional requirements of the growing puppy and kitten have largely been established by determining the nutrient level at which maximum growth occurs without much consideration for other health factors such as immune function, future reproductive performance, physical capabilities, or disease resistance. As our understanding of nutrition has expanded, it has become evident that the nutritional influences of early life are the foundation for future health and longevity. New research in pediatric nutrition seeks to define nutrient requirements using indicators beyond that of achieving maximal growth and also to understand the impact of early nutrition on lifelong health. With this awareness, it should be no surprise that the nutritional management of the canine and feline neonate begins before birth.

REPRODUCTION

Maternal malnutrition can have a significant impact on reproductive outcome and is a major factor in intrauterine growth retardation and mall-for-gestational-age human beings and animals.14 Although the preise m chan ism is not well understood, maternal nutrition can alter

horm n s, ytokines, and placental functions that control implantation,

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370 KIRK

embryonic differentiation, fetal growth and development, and parturition. 14 Recently the concept of Ufetal programmingU has been more widely accepted. Several studies in animal models and human subjects have described the programming of select fetal genes by the perinatal nutritional environmenty,44 Fetal programming can increase the risk of developing chronic disease such as diabetes, heart disease, or allergies later in life or result in a variety of permanent behavioral abnormalities.17, 44 Interestingly, severe nutritional deficiencies that exist during a dam's development can result in immune impairment in her subsequent offspring.6, 15, 20 It is thus necessary to evaluate the dam to assess fetal nutritional adequacy.

Nutritional Assessment in Reproduction

The steps involved in providing good nutritional management are to systematically assess the animal; the food, and the feeding method. Once a nutritional assessment is established, correction or optimization of the feeding plan can be made. The initial evaluation starts with a prebreeding evaluation. This should include an appropriate anamnesis, physical examination, and any necessary laboratory evaluation. The sire and dam should be genetically sound, in good health, and at optimum body condition. Although small variations in body condition can be corrected during pregnancy, breeding should be delayed in animals that are significantly under- or overweight (body condition score [BCS] < 2 or > 4.5 on a 5-point scale). Obesity and undernourishment can be detrimental to reproductive performance and neonatal health. Malnourished dams may fail to conceive, abort, or bear small underweight young.8, 22, 23 Lactation failure is particularly common in malnourished queens. Overnutrition, or obesity (BCS = 5/5), has an equally negative effect on pregnancy outcome. Stillbirths, dystocia, and cesarean sections occur more frequently in obese queens compared with those at ideal body condition.24 Similar results have been described in dogs and people.8 The mechanism may, in part, be the result of altered nutrient transport across the placenta to the fetus. Hormonal and nutrient concentration in the dam alters transcription and translocation of specific nutrient transporters in the placenta and regulates placental growth. 15

Unfortunately, suboptimal nutrition and mild deficiencies are often difficult to determine in a clinical setting. Even in severe fasting or chronic dietary restriction, fetal malformations are uncommon. Thi is likely a result of maternal catabolism and release of tissue micronutri n ts that strive to balance the fetal diet at the expense of th d a ll).' ~ d'OHi'>

fetal deformities are more typical of single nutrient d fi i 'n i ' S or n Ol1

nutritional causes. Nevertheless, early f ta I IOSH, prell) , lu rc dd i V(, I' , low birth weight, failure to thriv , and in r(,fl. '(·d O{'('III"I'(' IJ( '(\ (I f 1'"11 1111il lil death have all been nltriblllc'd hI I'Iw Illon ' \" '1111111111 ('111111 '/1 01 1\1 ill 'l'll llI malnutrition, I'l lori (' tI( ·(j eil , or (', d ill'il' 1' 1( 1', 'I I . "

In :Hldiliol1 iii I ' ll 111 111 /', IIPIII 'I' I' IIIII,' 111111 \, 1I'Ihili il ll dlld " '11'1) ',\

NEW CONCEPTS IN PEDIATRIC NUTRITION 371

balance, a nutritional assessment should include close scrutiny of the food and feeding method. Nutrient levels during gestation should meet established requirements for reproduction (Table 1). Marginal intake of key nutrients is best corrected well in advance of breeding, as correction during gestation may too late. Copper levels adequate for adult maintenance but deficient for gestation resulted in reproductive failure, early abortion (25 days), and fetal deformities in one group of queens despite dietary supplementation at breeding (Fig. 1).10, 22 These observations suggest that timing of nutrient availability is critical to normal embryonic growth and differentiation or that maternal tissue repletion or placental nutrient transfer may be inadequate to compensate for deficiencies during critical periods of need.

Key Nutritional Factors in the Dam during Gestation and Lactation

There are few studies establishing the minimum nutritional requirements for the reproducing dog and cat. Many recommendations are extrapolated from growth studies, data from other species, and clinical experience. Although most foods appropriate for growth are adequate for female reproduction, certain nutrients are required in higher amounts. Nutritional claims for nutritional adequacy during reproduction should be supported by successful feeding trials during gestation and lactation. Careful attention to pet food labels is important. Newer foods designed to reduce the risk of developmental bone disease in large-breed puppies or to maintain urinary tract health in the adult cat are not ideal for gestation and lactation. A summary of key nutritional factors for reproduction is found in Table 1. The following sections describe in more detail key nutritional factors important to the growing fetus and neonate.

Water

Water needs increase during normal reproduction. Expansion of extracellular fluid compartments and maternal and fetal tissues during pregnancy increases the need for water. Water is particularly important for milk production during lactation. Water needs during lactation vary D cording to the maintenance needs of the dam, type of food (canned vs. d ry), and ra te of milk production. Water requirements in milliliters P ' I' day a 1" approxim.ately equal to the energy requirement in kilocaloI'i 'So I\) t, bl ' Wil t r should b available at all times. Feeding canned foodH or l1 dd i ng more wn t I' d iI" tl y to food can improve water intake i ll Ihol'll \ t1dl11 l'l I'l' l IIl'1nn I 1\ ) drinl .

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Figure 1. The effect of dietary taurine deficiency in a queen at 45 days' gestation. The placenta is underdeveloped with poor vascularization. A partially reabsorbed embryo remains attached to embryonic membranes and is visible at the center of the opened placenta.

"nutrient." The pattern of energy intake during reproduction differs between dogs and cats (Fig. 2). In the queen, energy intake and weight gain increase linearly from conception to parturition. The recommended energy allowance for feline gestation is 25% to 50% above maintenance levels or approximately 90 to 110 kcal/kg/ d. The energy increase can be accomplished by providing 1.6 times the resting energy requirement (RER; RER = 70[body weight in kg]o.7S) at breeding, with a gradual increase to two times the RER at parturition. In the dog, energy requirements remain at adult maintenance (1.9 times the RER) during the first two thirds of gestation and peak at 30% to 60% above maintenance during the last third of gestation. Beginning at week 4 to 6 of gestation, gradually increase energy intake to 30% above maintenance by whelping. Because of individual variation and increased energy needs in dams with larger litters, energy requirements may increase to 60% or more above maintenance levels. Free-choice feeding allows the dam to adj ust food intake as needed to meet her energy requirement for gestalion. This is th preferred method of feeding the queen throughout )' 'HITlli o n an:t 18 tat ion. Dogs in arly gestation and obese-prone queens li i10lJid Iw nwn l-fed to on ll"o l ex 'siv food intake and maintain opti-111011 hod wvig ill .lIHI nil'l' of gain . Ili ~hly dig s tible energy-dense foods 1)('11' III lill 'I'1 Ldl ' )',I 'H t. Ii II)l 1 ('l\ lpl'i{' ilil ,d ('Ii ('i' minimize stomach fill to Idl ll\1\1 II\ IlII ' ,il ll lll lllll llI l IPI\I 'I' 1111 ' IIII' )',1' \vitl \ll t'I'II H, 1\(1'('1' I art lll'iti on, th 111 1i h 1IlI liid WI' I)',II I,"" III III"" I!I III \' I' 11 1I 11I 1·11I '1'I .d lll )" w(' I),,111 III lYIoin!:.,il 11I11 'IJl I,III ' 1,"11111111 'IIII' '111"1'111\ I til ,111 \ ),,1 1111 1111\ ,,, Id 1111I1,til)()() )', ,!I l()VI'

374 KIRK

40 900 -- Body weights = Energy intakes

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Figure 2. Comparison of the pattern of energy intake and body weight (BW) gain during gestation and lactation in the dog and the cat. A, The queen gains 'weight in a linear fashion throughout gestation and then draws on body stores to maintain lactation. Weight loss during lactation is substantial despite an energy intake 2-3 times above maintenance levels. B, The b itch gains weight in the last trimester at which time food intake will increase by 30- 60%. At parturition she should weigh 5-10% above the premating weight and gradually return to this weight by weaning. RER = resting energy requirement. (Adapted from Debraekeleer J, Gross KL, Zicker SC: Normal dogs. In Hand MS, Thatcher CD, Remillard RL et al (eds): Small Animal Clinical Nutrition, ed 4. Marceline, MO, Walsworth Publishing Co, 2000, p 235; and Kirk CA, Debraekeleer J, Armstrong PJ: Normal cats. In Hand MS, Thatcher CD, Remillard RL et al (eds) : Small Animal Clinical Nutrition, ed 4. Marceline, MO, Walsworth Publishing Co, 2000, p 321.)

prebreeding weight. Queens failing to gain ad qu at w ighl' durill ); gestation have suboptimal lactation perform, n (' .

Lactation is the most ener y-d mandin l'l f lll)',I ' or li rv. Pl'liI IIdll production typically oc urs nt ~ I;() II. w(I(II /4 ()I 1.11'l.llillll , '1'lli 'I)('l'I i!' di y, peak energy d m, nd ~ hll i dd l'pill<'iti l' willi 11 11 11 11I' 111l ti , ' .(iI I dl 'I(l lllI y OC UI'S ,I ) II) 7 WI'!, I I p OI I(1 I1 I'111I11 11, '1 1 ' ''II'I)', \' 11 \' 11111'1111' 11 1" III II}


exceed two to six times the RER. The discrepancy in the timing of peak lactation and peak energy demand is a result of combined food consumption by the dam and offspring. Neonates begin eating the dam's food in increasing amounts from 3 weeks of age until weaning. Even though there are several useful guides to estimate the energy requirement of lactating dams, it is preferable to feed free choice. A wide variation in energy needs makes accurate prediction difficult, and free access to food encourages early food exploration and consumption by the neonate. If controlled intake is required to avoid excessive weight gain, two to three daily feedings are recommended.

Protein

During gestation, the protein requirement increases from 40% to 70% above maintenance. Minimum recommended protein intake is 6.3 g of protein per 100 kcal (25% dry matter [DM]) in the bitch and 7.5 g of protein per 100 kcal (35% DM) in the queen.S• 22 Protein quality and quantity are important to provide essential amino acids for growth and development of the fetuses . Animal-based proteins are preferred as the major contributor to dietary protein because they generally have greater digestibility and more desirable amino acid profiles. Improved protein quality enhances newborn vigor and reduces neonatal mortality.32 Protein deficiency during pregnancy may result in lower birth weight, higher neonatal mortality, and lowered immunocompetency.6.32 Proteinrestricted foods fed to queens during late gestation and lactation resulted in abnormal behavioral development such as delayed home orientation (ability of kittens to orient to and return to the nest), aberrant locomotor development, and decreased emotional responsiveness.12

During lactation, the dam increases protein synthesis to supply milk with protein concentrations suitable for growth (approximately 36% DM milk protein) . In queens nursing large litters, daily milk protein output may reach 19 g of crude protein per day by a 4-kg cat. It is not surprising that protein needs during lactation exceed even gestational requirements. Inadequate dietary protein concentration results in poor lactation, slowed neonatal growth, and impaired immune function.33

Taurine

Tal.lrin defi ciency in gestating queens may result in fetal death near I'he 25 th day of g ta tiol'l , abortions throughout gestation, fetal deformity, low birl'll wt' i ~h t, and d lay d rowth and development.42 The taurine l'l'tjllil'l' I1Wnl (01' rvp rotiucl'ion in I'h, atis similar to that at other life HI,,!;!, : .I Illinill1llll1 of 11.1 % I)M la LlI' ill t' in d r food and 0.25% DM in (11111111 ' .1 II HH III, ~; IIJl(lI( ' Il l\' lll i ll )', Idlll'il lI' 10 1% I)M hns res ul t d in li ghtly

111111'11 I,d l'I' I" lI lilll ' l VI' 1" ' 1'111 1'111 .1 11"1 ' " ' 1'11 11'1 11 1 hili Illwv l' kil'tcn )!; rowth l 'l il l' I ' () II I' I' 1I1 1' 111 I ll', 1'111 111111 ' 11 Ld 1(1111 1/1 111'1 )', II"1i 10 1' I'I 'p I'IH IIIt ' li o l) il J'l'

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376 KIRK

lated homemade foods or dog foods are more likely candidates. Taurine is not a required nutrient for canine reproduction.

Fat and Essential Fatty Acids

Because of the increased energy demand during gestation, highenergy foods are beneficial. Fat delivers over twice the amount of calories as the same amount of protein or carbohydrates and represents an important source of calories. In studies comparing the effect of two different foods on reproductive performance, higher fat foods resulted in improved birth weight, survival, and growth compared with a diet containing lower fat.31 Fat levels recommended for reproduction are listed in Table l.

Linoleic and a-linolenic acid are essential in the diet of cats and dogs. Arachidonic acid is essential in the cat, and deficiency results in reproductive failure.29, 34 Essential fatty acid deficiency has been associated with small litter size, low birth weight, preterm delivery, and poor placental development in a variety of animals,21 Current recommendations by the Association of American Feed Control Officials (AAFCO), US regulatory standards, are appropriate for gestation and lactation but do not provide recommendations for essential omega-3 fatty acids (W-3).1 A dietary source of docosahexaenoic acid (DHA; 22:6w-3) is required for normal development of retinal function in nursing kittens and children and possibly in puppies.35 In young female Beagles fed w-3 supplemented foods, there was an earlier onset of first estrus, larger litters, and fewer stillbirths compared with similar previous breeding groups with low w-3 intake.21 Milk concentrations of DHA parallel dietary intake by the dam; thus, DHA should be included in foods fed during lactation. Common ingredients such as fish, fish oil, and poultry meal represent a source of DHA in commercial diets. .

"'" Calcium and Phosphorus

Calcium and phosphorus are required at levels greater than maintenance to support fetal skeletal development and lactation (see Table 1). Calcium supplementation is rarely indicated except to balance a homemade food or to treat animals with eclampsia. Concerns exist ov r excessive calcium intake during gestation and its role in prOln oting eclampsia or skeletal abnormalities in the offspring. To date, high d i.eta ry calcium during gestation does not seem to increase the risk for ' lDl1Ips in or developmental bone disease in dogs.40 Nevertheless, ex essivc < Id lll11 intake during early growth is a significant ri kin la r -brc I I til Ii '. ', Because puppies begin to eat the m at rn al diel' nl ::\ wt'vI H, Il IlrOI1l'I' calcium and phosphorus 1 v !1 ( nd roti o in Hw 111 11 1\'t'llll I tii('1 i ' jlllporl.IllI , Moderate 81 ium nnd plHIHpilorllH inl.ll;;, ' "1.1 II ,' II" il llll !pll(l1 pll(ll II ratio o f 1.1 : 1 10 15: 1 fl l'l' 1'I ' III'OI'I'i III, ',

NEW CONCEPTS IN PEDIATRIC NUTRfTION 377

Carbohydrates

Low-carbohydrate foods have resulted in maternal hypoglycemia and ketosis in late gestation, low birth weights and neonatal deaths in puppies, and excessive weight loss and poor lactation in queens.33, 38 Dietary carbohydrates spare protein required to sustain blood glucose concentration during gestation and provide substrate for lactose synthesis during lactation. Increasing dietary protein levels reverse the effects of carbohydrate-free foods in gestating dogs. Lactation performance is improved by providing some dietary carbohydrate to queens even in the face of abundant dietary protein.33

Other Nutritional Factors

Digestibility

Foods with more than average DM digestibility (> 85%) are best suited for reproduction. The benefits of highly digestible foods include (1) improved nutrient availability to meet the increased nutrient needs, (2) reduced required food volume and subsequent abdominal fullness, and (3) avoidance of large amounts of undigested nutrients entering the colon, which can lead to diarrhea.

Urinary pH

Highly acidified foods should be avoided during gestation, as they may impair bone mineralization in the developing fetus. Anecdotal reports have implicated certain highly acidified semi-moist foods in poor reproductive performance in queens. Foods designed to produce average urinary pH values at or above 6.2 seem to be safe during reproduction.

Monitoring

One of the early indicators of successful breeding and conception in the queen is a steady gain in body weight (see Fig. 2) . In the queen, w ight gain increases linearly from conception to parturition. This patt I'll is different from that of dogs, which experience small increases in hody wight until the last third of gestation, when weight gain and (' Iw rg in t. I ' g r otly in I' a ' . Wight gain in early pregnancy is not dHHocinlt'd wilh Hignifi c< nt grow th of I' productive tissues or the concepIUN bill '("' 111 1'1 10 lw slo t', 'd in ,' nl' rgy d pots (PI' sum ably as fat) to /1I IPIHli 'l Illl'I ltlil lll , )(11 ,, ' 11/1 IIIld" t' WI,jl', ill ,II pnrlurili Ol1 of I: n xp ri nce 1' (l IH ' IlI d ,tl i'"1 1)('1'1111'11111111 '" 111 11 1 ",, !>l llly III IIll1 illll ili hi lt! ,'(lllliilio)') , MI 'I III WI' )',111 )',1 1 II 11111 II )', ),," 11 1,11 11 11 II ' 1"" "11 11 I I ,qll' I'Il \ IIII III " ly \o()% ll f 111" 1" "1 111 11111 )" \\I1'1)', It! (' Hili I ' (11 ) ),, 1111 ,1\" '101 )',1' 1111 , '1 I ' ) ' '1\' 111 1'1111 I Ill ,' I , li ll ,llIlIilti 1111 11'1111, 111 '1 111111 \ \ " 1),,111 I.\, .1,"" il l \\, 11, ,11 11 11)', \ 1 Iii 11111 1

378 KIRK

tion, the queen loses only 40% of the weight gained during gestation. The remaining 60% of prepartum weight gain is used during lactation to sustain milk production. Unlike the queen, the bitch enters lactation at only 5% to 10% above prebreeding weight.s The mammary glands should be closely evaluated to ensure health and ready access. Expressing milk from each gland does not ensure adequate milk production. Continuous weight gain by the offspring is the best indicator of lactation performance.

GROWING PUPPIES AND KITIENS: NEONATAL PERIOD

The neonatal period encompasses the time from parturition to completion of weaning. During the nursing period, the neonate relies on colostrum and milk to supply its nutritional needs. The nutrient profile of maternal milk is thought to provide optimal nutrition for the neonate even though larger growth rates have been observed in puppies and kittens fed milk replacers.36 Nutrient recommendations for neonates have been derived from the composition of maternal milk (Table 2) and growth studies in weaned puppies and kittens. Milk provides benefits

Table 2. NUTRIENT COMPARISON AMONG MILK OF VARIOUS SPECIES

Queen Bitch Cow Goat Nutrients Milk' Milkt Milk:!: Milk:!:

Moisture (g/100 g) 79 77.3 87.7 87.0 Dry m atter (g/lOO g) 21 22.7 12.3 13 Crude protein (g/100 g) 7.5 7.5 3.3 3.6

Arginine (mg/100 g) 347 420 119 119 Taurine (mg/ 100 g) ' 27 0.13 Methionine (mg/ 100 g) 188 82 80

Crude fat (g/100 g) 8.5 9.5 3.6 4.1 Lactose (g / 100 g) 4.0 3.3 4.7 4.0 Minerals

Calcium (mg/100 g) 180 240 119 133 Phosphorus (mg/100 g) 162 180 93 111 Potassium (mg/ 100 g) 103 120 150 204 Magnesium (mg/ 100 g) 9 11 14 14 Copper (mg/lOO g) 0.11 0.33 Iron (mg /100 g) 0.35 0.70 0.05 0.05

Metabolizable energy (kcal/100 g) 121 146 64 69 Metabolizable energy (kJ/100 g) 506 610 268 2H8

' Data from Adkins Y, Z icker Sc, Lepine A, et al: Changes in nu[!'i ('nl fll1d I 1'01" ill (,(" " pn"i I iOl1 01 cat milk during lactation. A m J Vet Res 58:370-375, 1997; and Zollmnn il, I )"h" I1 I'l"kt 'I' il, l<il 'lwk II, 1'1 al: Investiga tions on milk composition and mil k y ield in QU Cl' I1" 1ItI'" I" 1t1 I) , I" l 'I'Ott,,'lI ll1f',1I 01 11 11 ' Waltham International Symposil "'), Orlancio, 1')97,

tDatafrom Meyer H, K i ·nzl(' 11, f),,,,,,, "" '11 I ': M lIl'IlI'H' I1 f',1" ''' lt l MI I, III IIIII "' I" """i1 ,I/' ''" f1 I 'l'l "lid Hiindin sowie Futtcrau fnnhl11 \' !l 1l1! (;,Iw!t lli IHI II WI, ll li ilg 11 111 1' Ih ll l 1'11 11 I II \I HIIII 1I111 111d lt II, ' III , 1111 Tierphys iolof,\ il' "nd 'l'II 'I'I' I1ll1 ll1 l1 lf; (Ad"""" ,. III A" I" " II l 'Ii VIl III IIIII\ 11 ".) \ ,11,,," 1 t~"IIIIIIIII) 11,', 1 '" ·19R5.

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beyond a supply of nutrients. Enzymes, immune factors, hormones, and digestive factors serve important functions in the developing neonate. Although it sometimes becomes necessary to hand-feed puppies and kittens less than 4 weeks of age, it is probably better to foster or supplement feed than to completely deprive the neonate of maternal milk.

Neonatal Assessment

Nutritional assessment of the neonate requires regular evaluations beginning at birth. A nutritional assessment should include the dam's history and a detailed physical examination, including body weight, temperature, muscle tone and vigor, and behavior. At birth, kittens should weigh approximately 100 g. The birth weight of pups varies by breed (75-700 g) . Both species should nearly double their weight in the first week of life. The neonatal kitten should gain between 10 and 15 g daily. Gains below 7 g/ d are inadequate. Puppies should gain 2 to 4 g/ d/kg of their anticipated adult weight.s, 22

Caretakers should be encouraged to keep logbooks of all data that may provide information about the health and nutritional status of the neonate as well as about · the reproductive performance of the dam. Records should include food intake, body weight, body temperature and stool characteristics, especially during the first 2 postpartum weeks. Successful management depends on the quick recognition and correction of health, nutrition, and management problems.

Key Nutritional Factors in the Neonate

Colostrum and Milk

Colostrum provides nutrients, water, growth factors, digestive enzymes, and maternal immunoglobulins, all of which are important for the development and survival of the neonate. Colostrum differs from mature milk in water and nutrient composition. In addition, non-nutritional factors change concentration over the course of lactation. The pa ttern of ch ange is similar between dogs and cats, although not identi' I) I. In g n ra 1, tb DM concentration declines as water content increases from day '1 to 3 of lac tation . Lactose concentrations are low in colostrum (- -30 I!;/ I, or 25 I11g/ k al) and increa as milk matures. Protein and l ipi I i('vvls tk cl int' mari e JI from d, y 'I to . Tbi decline likely reflects III(' inili ,)1 (' 11,111 )',1' ill w,lt v l' ~' ll ltl l' lIt .IH cn loHlrlll11 transiti ons to mature lid II , l 'l'n l l'i ll I llv \ ' I ~ I'dH HIIHI 11 111 1 i l ll ' I'IW I' ii l ilihtl (\vt' r til' ('o llrsc of I,w l l tl ill il , ( ' II , lIl l',I '/i i l) 11 \1 1)1'1 .. 11 1'11111 1' 111 il il ll V1 II 'y wil it 1111)\ ' . (" II ('i llll1 111111

l"II '/ lJdl l lll li I 'P III 'I ' ltll" ll P il i 11 1 11'd lll' III' I II I !'I Y 1.1, w lli ' I'I '11i l 'II II, I 'II JiJ!I II',

II IH I 111 11)', 111 1 1 11 11 \ 11111< '1'1 111 111 111111 dl ' l l l l lI ' hll ii' I lldl, ' I " ' I HIIII '1i 111\1' 11111

li lli l l 1 111111 ' 1111 tl llI!' 1I II iI " ti , 11 11 11 I"II HI I"IIIIII>I 1111 111/ 11 1 11 11 1 II 'JlI"I ' III '

380 KIRK

milk. These values likely represent colostral milk (calcium:phosphorus ratio of 0.4:1) in that recent studies of queens' milk report calcium:phosphorus ratios ranging from 0.8:1 to 1:1 on day 7 and ratios reaching 1.2:1 by late lactation. Surprisingly, the maternal diet has a limited effect on the nutrient content of milk, with the exception of dietary fat and carbohydrates.

The neonate acquires passive systemic and local immunity from consuming colostrum or mature milk. Puppies and kittens should receive colostrum within the first 12 hours of life to obtain adequate systemic immunity (primarily IgG); after 16 hours, passive immunoglobulin transfer does not occur.4,7 Failure to ingest colostrum or milk during this period leaves the neonate immunologically compromised. This window of absorption is far shorter than that reported for large animal species, where adequate immunoglobulin absorption occurs for at least 24 hours.

Milk provides additional factors that help to regulate and enhance immune function. Components include cytokines and memory cells, which help to protect against antigens and pathogens and act as signaling factors within the intestinal mucosa.26 They also include proteins and enzymes that can inhibit or kill key pathogens. Certain oligosaccharides may serve as binding sites for pathogenic bacteria, thus preventing attachment at the intestinal epithelium.2o,26 Lysozyme and lactoferrin have antiviral activity. Maternal milk has thus been shown to inhibit important pathogens responsible for neonatal disease such as Camphylobacter, Escherichia coli, Staphylococcus, and Rotavirus.26 The practical outcome is a lower incidence of gastrointestinal disease in animals receiving maternal milk versus milk replacer.

Other benefits of maternal milk include improved nutrient absorption, control of neQnatal growth and development, and promotion of , gut colonization with "host-friendly" bacteria. Milk-derived proteins known to facilitate neonatal nutrient absorption include such factors as lipase, lactoferrin, and vitamin-binding proteins, which aid in fat, iron, and B-vitamin absorption, respectively.26 Leptin, insulin, epidermal growth factor and insulin-like growth factor are all found in milk. The role of these hormones has not been clearly defined; however, they are thought to influence gut maturation as well as body composition and growth. Nursing animals and human infants have less body fat and weigh less than formula-fed neonates.26,36 In people, this slower growth and lower body fat is associated with a lower incidence of diab et an 1 heart disease in later life, . Milk from the bitch and queen varies marl<edly fro m thnt of ru minant species, Consequently, mill< from these alternotiv 81 t' ics is nol suitable as the sole source of nutritiol1 f r nurs in g I ill'(' ns 11 11<1 pllpp i l 't . Replacement formula with c i'l litri I t pl'Ofi l(, Sil l)i lll l' I'() Ihnl I ll' 111 ,)1111'1' mill< shoul d b uS d fOt' o l'J hnnH nnd , (lp pll'Il H' l1 l. d f(l(ld lll )', ll (11(11' '111 1111' 2).


Energy

Maternal milk typically meets the energy requirements of the neonate. Estimated caloric intake is approximately 200 kcal/kg of body weight up to 4 weeks of age. By 6 weeks of age, male puppies and kittens are significantly heavier than female puppies and kittens and consume a proportionately larger quantity of food. At this stage, energy requirements are approximately three times the RER until the animals reach 50% of their adult weight. As a rule, milk contains from 0.85 to 1.6 kcal/mL (average, =1.46 kcal/mL) and milk replacers contain approximately 1 kcal/mL as fed.

Water

Total body water of the neonate is nearly 30% greater than that of the adult animal. To maintain adequate hydration, the water intake of the neonate is relatively high, A normal neonate needs about 130 to 220 mL of water per kilogram of body weight per day.

Protein

The minimum protein requirement of the nursing neonate has not been established but is assumed to be comparable to that of weanlings. The AAFCO crude protein recommendations are 22% and 30% DM for puppies and kittens, respectively. The protein content of maternal milk is greater than 30% DM in both species, however, and the digestibility of milk protein is nearly 99%. As a result, the nursing neonate typically ingests protein levels greater than those recommended by AAFCO.

Taurine

Taurine is important for normal growth and development of kittens. Queens' milk supplies about 400 mg/L of taurine. Queens fed lowtaurine foods have significantly lower milk taurine levels, which can impair normal growth and development. Cow's milk is a poor source of taurine (i.e., only 1.3 mg/L). Homemade milk replacer based on cow's milk should be supplemented with taurine.

Fat

Mi ll f:1 1 is , n impor tant source of energy and essential fatty acids C(lj' Ill l' I)VI I II ' l ll' . Uillil c most ther nutrient, the fat composition of the d ll ll ) '~l Ii It 'I ('(I I ) 11i)" n i n ell nil ill n u('n('(' m ilk fat quantity and quality. M,1I1 '1'1\ tI III II I, 1" 'lIvl ti l' Il ll' ('I'll'll ' j II lit! filII lI e itlM I inol 'i (;), id, arachidonic I I( ' d f II lld 1111 ;\ 1111/\ /1 ('1 11' 111 111 1 1(11 ' I )O I'l llI " 1'\'Ii ll,t! 1i ('v I· lnl 11 1cnt and 1II I1I 1 ( III II II Il fl li ll, ' l ld l 'l d ld ll 'll Ililti l " ll l lollrl y 111 ti t))',I) . II'

382 KIRK

Calcium and Phosphorus

Calcium concentrations in dog and cat milk are approximately 1% DM by middle to late lactation. The calcium:phosphorus ratio is approximately 1.2:1 at 1 week and remains so throughout lactation. The maternal diet has little influence on milk calcium content. Nevertheless, it is important to note that calcium supplementation to large-breed puppies between 3 and 6 weeks of age resulted in significant enostosis and developmental bone disease.16,40 Growing puppies have passive calcium absorption until several weeks after birth. During this time, they cannot regulate calcium absorption across the gastrointestinal tract below 40% of the ingested amount.16, 40 Because this period often coincides with initial food exploration and weaning, it becomes critical to provide foods with proper levels of calcium and the correct calcium:phosphorus ratio to large- and giant-breed puppies (Table 3). Calcium supplements should be strictly avoided, except to balance a home-prepared diet or to treat a specific disease.

Trace Minerals

Dog and cat milk contains iron, copper, and zinc concentrations markedly higher than those in human and bovine milk. Copper and iron levels tend to gradually decline throughout lactation, whereas zinc concentrations remain constant. Mineral deficiencies are rarely reported to occur in nursing kittens and puppies fed maternal milk. Occasionally, iron deficiency and'\mild anemia may occur at 3 to 4 weeks of age if insufficient stores are not accumulated during gestation and the first week of life. Fast-growing large-breed puppies seem to be at greatest risk and may be treated with iron-containing supplements or early provision of good-quality food.8 The occurrence of iron deficiency should , prompt an immediate review of the food and feeding practices of the dam before and during gestation.

Feeding Plan

Foods should be liquid until puppies and kittens are 3 to 4 w e ks of age, when semisolid to solid foods may be introduced. Foods m, consist of maternal milk or milk replacer. Maternal milk i con id " I' 'd ideal because it provides all the essential nutrients, antibodies, ll ZY IJl l'S,

and hormones. Commercial and homemade m ilk r pi a ' f S may mimic the essential nutrient content of maternal mi ll but In li tH Ol'l'WI" hl' lldi cial properties. The quality of milk and mi ll 1'('1 1:ICl ' I'S i, ' diCnculi 10 assess without analysis. Measul' l11 ent or IWOI) ,ll.ll )',I'ow li) L I m h,lld the most practical m tllOc! of :1:-;:-;(':-; :-; 111<'111.

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2 to 4 hours during the first week of life and then every 4 to 6 hours until weaning. Cold neonates do not suckle and have reduced gastrointestinal function. It is thus imperative to adequately warm weak puppies and kittens before they are fed. Hypoglycemia and hypothermia may occur simultaneously in neonates and have similar clinical signs. If kittens or puppies fail to respond to warming, a dilute glucose solution (2.5% glucose) may be given orally. This should be repeated until kittens are able to initiate a strong suckling reflex.

Monitoring

Nursing puppies and kittens should be reassessed daily by the owner or breeder. If the neonate fails to thrive, is weak, demonstrates restlessness, exhibits excessive vocalization, or has a bloated abdomen, it should be evaluated together with the dam. These signs may indicate insufficient milk production or quality or another disease process. Puppies and kittens that are well fed should grow at the previously described rate and remain content between nursings.

GROWING PUPPIES AND KITTENS: POSTWEANING PERIOD TO ADULTHOOD

The postweaning growth period includes weaning until adulthood (i.e., 10-12 months). The nutritional needs for growth include maintenance needs similar to those of the adult and energy and substrates , necessary for rapid tissue accretion. The growth rate slows if nutritional deficiencies exist. As is the case during other stages, a nutritional assessment evaluating the animal, diet, and feeding method should be performed. The general health and risk factors should be determined during the growing phase. A thorough history and physical examination, including determination of body weight and condition, are generally sufficient.

The rapid growth rate continues until the animal reaches 5 month ' of age and then slows as the kitten or puppy approaches 80%, of ad u I t size. Large- and giant-breed dogs mature somewhat later. Most at8 an dogs achieve skeletal maturity by 1 year of age. Additiona l W 'i )" ht go in may occur after 12 months and represents a p hase of maturn [i o f) <l lll! muscle development. There is no evidence thnt th a~' nl' IWliI"t' I"iI) )', alters the rate of growth. Unfortunate ly, en 'rgy rC'(l'lirvlll (' n l. dOl" li lll' with neutering, and I·h · ri sk fo r 01 cH il inCI"('IIKl'S . ()I v 'il Hhuilid IH' pr v nt d at ( n ('11 1" 1 :11',1' IWI' II 11 ,' (' or it. ~.d); II in\ ' i lill illljl l(' l 0 11 1lI '.lilh II l1d 10 1 gc'v il .


Key Nutritional Factors during Postweaning Growth

. Many of the key nutritional factors were discussed in the preceding section, and recommended levels are outlined in Table 3. The following sections highlight factors to consider once the neonate is weaned.

Energy

Growing puppies and kittens require substantial energy to meet the needs of rapid growth, thermoregulation, and maintenance. Ensuring optimal growth is desirable, but excessive energy intake may contribute to obesity or developmental bone disorders in large- and giant-breed dogs. Eight-week-old puppies and kittens have an energy requirement of approximately three times the RER, which declines to adult levels near 1 year of age. Neutering reduces energy requirementsY, 39 After neutering, limiting food intake or decreasing dietary energy may be required to prevent excessive weight gain or an excessive rate of growth.

Protein

The protein requirements during growth reflect essential amino acid and nitrogen needs for tissue accretion. In kittens, protein also provides sulfur-containing amino acids, which are required in greater amounts than in other species. A source of animal protein is best for the cat. Although the role of high-protein diets as a cause of developmental bone disease in dogs has been refuted, excessive protein levels are not generally advised.30 Amino acid levels compatible with AAFCO recommendations seem adequate.1

Fat

Dietary fat serves three primary functions in growing animals: it supplies essential fatty acids, it acts as a carrier for fat-soluble vitamins, and it provides a concentrated source of energy in the food , Excessive fat contributes to obesity and other health-related problems, however. In the large- and giant-breed dog, excess energy intake is a key contributor to the occurrence of developmental skeletal disease. The AAFCO minimum recommendations for growth are 8.0%, 0.5% and 0.2% for total fat, lino] i.c acid, and arachidonic acid, respectively. These levels sustain <ld quate growth. Faster growth rates are achieved with higher fat intake bll t may hav negat.ive health consequences in the large-breed dog,

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386 KIRK

perparathyroidism as a result of dietary calcium deficiency is the most common cause of nontraumatic orthopedic disease in cats in Utrecht. 16

The minimum requirement for dietary calcium in growing kittens is approximately 5 g/kg of food (0.5% DM), although levels of 0.8% DM are more than appropriate for nursing, weanling, and postweaning kittens.22 Unlike the situation with puppies, calcium excess in kittens is not associated with developmental orthopedic disease. Nevertheless, extremely high concentrations of calcium can significantly reduce magnesium availability in the caUB

Both excess and deficient dietary calcium can promote skeletal abnormalities in puppies. Although nutritional secondary hyperparathyroidism and osteoporosis may result from calcium deficiency, a more common concern is the risk of developmental skeletal disease as a result of calcium excess in large and giant breeds. Several factors influence the frequency and severity of skeletal disease resulting from improper calcium intake (Table 4). Because calcium homeostasis mechanisms are poorly developed in the young, increasing dietary calcium results in increased calcium absorption and retention. Foods for large- and giantbreed puppies should provide 0.7% to 1.2% DM calcium in a moderately energy-dense food (3.2-3.8 kcal (of metabolizable energy (ME) per gram of DM). Phosphorus levels influence the utilization and balance of calcium. The calcium:phosphorus ratio in the dog should be maintained at 1.1:1 to 1.8:1. Small-breed dogs are more tolerant of a wider range of dietary calcium and phosphorus (see Table 3).

Potassium

The potassium requirement of kittens is dependent on the protein content of the food and the effect of the food on acid-base balance., Urinary potassium loss is markedly increased when kittens are fed high-protein or acidified foods. To avoid syndromes associated with hypokalemia, kittens should not be fed highly acidifying foods, and potassium allowances should be at least 0.6% DM intake.

Other Nutritional Factors

Diet Acidity

The urinary pH of growing kittens is lower than tha t of ad ult ats fed similar foods . Presumably, the lower pH is caused by hydrogell ions released during bone formation, which are excre t d in to the lIriIW ." Excessive dietary acidification may re 'LIlt in poo r bOlw mincnlii l',fl li ol1 and growth. Thi incr ascd I' SF OI1fK' to di('i'o!' nei lifi cn li()1l VO ld l"" ('H tmtil kitt ns a rc nl pf'() ill\ ;rl l'1 I monlh, of .1)',(' . I 11 1( '11 14 ho(d" 11 1)1 il, ' rt' cI ,food H 11 ~' 11 prodlll '" 111 'ill l ll 'Y /1I1 V.lill, ' 1 1, ' 1/ Ihl ill I,: ' W ill ' ll Ii'd 11 '( '1'

('hO II'I' , I I(lo d / 1111 rI II) ',I IYI'I ,.ill II IVI' 1\ II If "" 11 1' llli ll l pi I


Table 4. FACTORS THAT INFLUENCE THE RISK AND SEVERITY OF DEVELOPMENTAL SKELETAL DISEASE IN LARGE-BREED PUPPIES

Factor

Dietary calcium

Age of onset

Duration of excess

Phosphorus level

Caclium availability

Growth rate

Dietary energy

Feeding method

Protein content

High Risk! Increased Severity

> 3.0% dry matter

3-17 weeks

Weeks

> 1.4% dry matter

High

Rapid

Calorie-dense

Free-choice

No effect

Rationale

Puppies are unable to regulate calcium absorption until they are several weeks old. High calcium intake results in passive gastrointestinal uptake, hypercalcitonism, decreased osteoclastic activity, and decreased bone modeling.

Excess calcium between 3 and 6 weeks (partial weaning) results in the most severe abnormalities in calcium balance; however, calcium is poorly controlled through at least 17 weeks of age.

Chronic intake during a susceptible age results in hypercalcitonism and parathyrOid atrophy.

The effect of high daily calcium excess is exacerbated by concomitant high phosphorus intake.

Certain calcium salts (e.g., calcium carbonate) are more absorbable than other sources. They can exacerbate dietary calcium excess through increased uptake.

Rapid growth requires greater bone remodeling and increased mechanical loading on bone and cartilage.

Energy intake directly affects growth rate and indirectly alters various hormones that stimulate chondrocyte proliferation and differentiation and bone formation and resoprtion. Fat is the major contributor to diet energy.

Ad libitum food intake or free-choice feeding allows excessive caloric intake. Free-choice feeding should be avoided, except with low-energy diets or underweight puppies.

Protein content of the diet enhances palatability and can promote increased food intake. Without excess food intake, protein does not increase the ri 'k of developmental skeletal disease.

388 KIRK

Digestibility

The food should be palatable and highly digestible (i.e., apparent DM digestibility> 80% and protein digestibility> 85%). The small stomach capacity and relatively high energy demands of young a~in:als limit food intake capacity. Providing highly digestible foods maXimizes use of the nutrients consumed and helps to avoid diarrhea.

Functional Foods and Nutraceuticals

The provision of specific nutrients or ingredients with functional properties beyond that of meeting basic nutrient needs is currently generating much interest. Recent findings establish th~ pos~ibility of altering body composition, immune competence, gastromtestmal function, and joint health in the growing animal through nutritional manipulation. Although few studies are specific to the growing dog or cat, the potential benefits provide exciting opportunities for enhancing the overall health of dogs and cats. In livestock, ingredients such as carnitine, chromium, and conjugated linoleic acid repartition energy stores and promote accretion of lean tissue over fat during the growth period. In a recent study, puppies supplemented with carnitine were larger with more muscle and greater bone mass and density than unsupplemented dogsY Chromium supplementation of Beagle dams d':lring gestat~on and lactation resulted in slight increases in the body weight of nursmg puppies but no specific benefit to the reproductive efficiency of the dam.2s

Chondroprotectives

Chondroprotective ingredients such as glucosamine and' chondroitin sulfate are popular dietary supplements and food additives for the support of joint health. Studies in adult dogs have shown mild to moderate benefits with chronic supplementation. In puppies, intramuscular administration of glycosaminoglycan polysulfate from 6 weeks to 8 months improved coxofemoral joint congruity and reduced the occurrence of coxofemoral subluxation in treated pUpS.28 Controversy remains over the bioavailability efficacy and mechanism of action of the various glycosaminoglycans. Nonetheless, glycosaminoglycan therapy has resulted in positive outcomes in dogs with certain orthopedic disorder . The long-term benefit to growing puppies and kittens is yet to b' determined.

Probiotics

Probiotics are microorganism Sli h ,Ii-! IlIlIIPdll llll',I'I )i, ' IlI lI 'I"1 ,I Ill '

yeasts fed to animals for th I uq ()K~' or l'q ',ld lll lll l'. II \! , 11\1, '/1 11111 11 11 111 ' I ,Ii the host. Th y hel ve' ht'( '1) II Hi'd Ilwl'I II li' III II ' dl ~1 11 111 1 IIlll l ril \, IIII II"II II v II


human beings and livestock to correct or normalize the microbial population within the gut. More recently, probiotics have been found to aid nutrient digestion and stimulate the immune system. Common organisms supplied as probiotics include Lactobacillus sp, Bifidobacter sp, Streptococcus thermophilus, and certain yeasts. The health-promoting effect of Lactobacillus includes improved food digestion as a result of microfloral enzymes that breakdown fiber, stimulation of antibacterial activity of Peyer's patches, enhanced IgA secretion, and a potential protective effect against allergies via modulation of the Thl and Th2 lymphocyte ratio.2 Lactobacillus can also stimulate macrophage function and increase the rate of apoptosis, a possible benefit in cancer protection.2 One study has reported alteration of gut microflora in response to probiotic therapy in puppies.3 The changes were short-lived, and specific health benefits were not determined in that study. Anecdotally, probiotics seem useful in managing diarrhea in response to antibiotic use in puppies and kittens. Probiotics may also prove to be beneficial in intensive breeding operations or large kennels, where stress, overcrowding, or unfavorable husbandry practices increase the likelihood of transmission of intestinal pathogens. For most puppies and kittens, however, good husbandry and sound nutritional practices are better options.

Prebiotics

Prebiotics are indigestible substances that provide substrate for the growth of healthful bacteria in the intestinal tract. Examples include a variety of oligo saccharides (e.g., inulin, fructooligosaccharides, manninoligosaccharides), resistant starches, and fermentable fibers. In addition to selectively supporting the growth of nonpathogenic bacteria, fermentation of prebiotics can help to reduce proliferation of gut pathogens, increase calcium bioavailability, and increase levels of short-chain fatty acids that serve as a major energy source for the gut muscosa. Certain prebiotics are thought to have a direct immunomodulatory effect as well as the ability to reduce hypertriglyceridemia and hyperinsulinemia. Negative side effects are rarely reported, with most involving mild gastrointestinal distress (i.e., flatulence, bloating, laxation).2,37 Data are limited on the benefit of prebiotics in companion animals. Although some studies have reported increased levels of Bifidobacterium and LactobaciLl.us in dogs and cats after the feeding of lactosucrose,19 two other :> tu d i reported negligible changes after the addition of fructooligosac-'harid s in either dogs or cats.41,43 Regardless of any alterations in gut

mi 'l"oflon1 or int stinal 111 rphol.ogy, studies demonstrating a functional hen ' fil on il111THl nC 'ta tu l:l, gnstroin t tina l health, or disease resistance il) pllPpil \ 11I Id I illl 'Ii , 111'( ' I(\cl ing.

II 114 111'1'11111111'" Iii 11 11 11 ,' II jll ', 'lrI ,' 1"'I'Ollllll t' lld Cl l'ions fo r th use of III'li ' l tll l, lI 1()(l tl lI ill 111 1'/11'111 l'I'I·III Ii II )I' II ll1d il'H II IIVI' d l' lll()ns lrat( ~ rl 1 11 '1 IlI il lI ll I)', 11111111'111 '" 1111 1'1'1\ ,1111 II\I Y 111\1 11',11 ' 1(II WIIIlIl / """ 111 1'. 1',I'(lW lhi 11 ,I W" Vil l, 11 11'1 ·111'11 111 11,\ ''1 111111 ' '1 11111 d l ll'IHII' 1111 '\"' 111 1111 , IIIIIII II II I', I'V Iy '111 '1"" 1,1 III ' .1 ,,11'1111111""

390 KIRK

Feeding Plan

A food that is complete and balanced for growth as demonstrated by AAFCO or similar animal feeding trials should be fed until puppies and kittens reach adulthood (10-12 months). Unmoistened dry foods and moist foods are appropriate. Semimoist foods that excessively acidify the urine (i.e., <6.0 pH) should be avoided until skeletal growth is completed. Identification of health risks such as obesity or developmental bone disease in large-breed dogs necessitates a scrupulous review of foods provided for growth. Treats are unnecessary but may be fed in small quantities (i.e., <10% of the daily intake). Milk is commonly offered to kittens as a treat. Amounts offered should be limited, because intestinal lactase levels decline shortly after weaning.

All feeding methods are appropriate for growing kittens. Free-choice feeding is preferred in kittens younger than 5 months. Conversely, regulation of excessive food intake by meal-feeding twice daily is preferred in dogs. Free-choice feeding and time-limited feeding are not always satisfactory in controlling food intake. Fresh water should be available at all times.

To determine the amount to feed, energy needs may be calculated based on age-appropriate requirements or determined using various feeding guides.s,22 After an initial food and amount is chosen, weight gain and body condition should be monitored to tailor the feeding amounts to individual pets. Poor weight gain, hair coat, and muscle tone along with inactivity and excessive crying are some of the signs of inadequate nutrition. A BCS above 3 (5-point scale), bloating, and diarrhea can be signs of overnutrition. All changes in appetite, body condition, attitude, or feces should prompt a review of the diet and feeding methods so that early corrections can be made.

SUMMARY

The ultimate goal of feeding puppies and kittens is to ensure a healthy adult. The specific objectives, however, are to optimize growth, minimize risk factors for disease, and achieve optimal health and longevity. Minimum nutrient requirements are easiest to determine in growing animals using growth rates as the nutritional marker. These level en u r a minimum level of good health in most animals. Never th I s, th ' optimal nutrient levels for growth may not represent the optima l. I 'v ,It; for other physiologic functions (e.g., immune function , di as' prevt'ntion, behavior). Nutritional requirements for growing <1 1 imnls nrc lwin ); redefined using physiolo ic param ters oth ' I' tho n v; r()w I h 1'0 I (' .

The most common < L1S 5 o f malnulrilion In Ill<' 1l('() I) li l' (1(' 111 10 111' protein-en rgy defi , it' llI ' or !)v('nJlllrilloll ill III(' 111'1"1 11 111. 11 pI ·I'II)!i. ~:I II )' II' mi rOn UITil'nl nh nol' ll w lilil'll [II'(' l'I ' I:ll lv I' ly 1111< '("11111'"1 N,'v I'I'lh"I" 1 , dll ' 11111rilinl)1I1 :1\ 11111 1 dill ' II)'. 111 '1)1 11 11 11 1 11( ,,, .01(11'1111 '"1 II " ". IIY II II I 1111"1 '1 fIj I ' 11l'111 ' i" llI 'i'w lilll 1111" III III IVI\ ,1 1111 11(111) 1, 11I1j'11I 1 II III 11111 1 111'111 11 111 111 III


tailor the nutritional plan to the individual at each life stage and to remember that pediatric nutrition should start before conception.

References

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128(suppl):2730S-2732S, 1998 4. Bouchard G, Plata-Madrid H, Youngquist RS, et al: Absorption of an alternate source

of immunoglobulin in pups. Am J Vet Res 53:230-233, 1992 5. Buffington CA, Rogers QR, Morris JG: Effects of age and food deprivation on urine

pH of cats. Vet Clin Nutr 1:12-17, 1994 6. Burkholder WI, Swecker WS, Jr: Nutritional influences on immunity. Semin Vet Med

Surg (Small Anim) 5:154-166, 1990 7. Casal ML, Jezyk PF, Giger U: Transfer of colostral antibodies from queens to their

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9. Dieter JA Steward DR, Haggarty MA, et al: Pregnancy failure in cats associated with long-term dietary taurine insufficiency. J Reprod Fertil SuppI47:457-463, 1993

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') I, I "" 1', 11 \1 111 I rvt A 11 1'111 1 III It! (I I 1,11 11 I IIi ', i', 11I1 !lilt' ,11111 Iil l 1I11 'III I'lI lI ll llI III 1,1I, 'I IIIII ,,. ill/· i\ III WIII 1( '1,".1 ,,11 111 '1 '11111 11 I I IIH~ III I I ' II \,~ III I "II' I 1111 1 li lli'" 1'11111

' I 1111 ·1"1 11 11 f\ 11I1I1I I I r-, llld dd I, " 'id 1111111 ,1111 1' III " I'IIIIII lliI 111 11'111> II I I V." H"II 1', I 1',1, 11' ,11 1'11 11

392 KIRK

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29. MacDonald ML, Rogers QR, Morris JG, et al: Effects of linoleate and arachidonate deficiencies on reproduction and spermatogenesis in the cat. J Nutr 114:719-726, 1984

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31. Olovson SG: Diet and breeding performance in cats. Lab Anim 20:221-230, 1986 32. Ontko JA, Phillips PH: Reproduction and lactation studies with bitches fed semipuri

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Nutr 126(suppl):10815-1085S, 1996 35. Pawlosky RJ, Denkins Y, Ward G, et al: Retinal and brain accretion of long-chain

polyunsaturated fatty acids in developing felines: The effects of corn oil-based maternal diets. Am J Clin Nutr 65:465--472, 1997

36. Remillard RL, Picket JP, Thatcher CD, et al: Comparison of kittens fed queen's milk with those fed milk replacers. Am J Vet Res 54:901-907, 1993

37. Roberfroid MB: Chicory fructooligosaccharides and the gastrointestinal tract. Nutrition 16:677- 679, 2000

38. Romsos DR, Palmer HI, Muiruri KL, et al: Influence of a low carbohydrate diet on performance of pregnant and lactating dogs. J Nutr 111:678--689, 1981

39. Root MV: Early spay and neuter in the cat: Effect on development of obesity and metabolic rate. Vet Clin Nutr 2:132-134, 1995

40. Schoenmakers I, Mol JA, Hazewinkel HAW: Hormonal calcium regulation and calcium setpoint in offspring of bitches with different calcium intakes during pregnancy. J Anim Physiol 83:1-14, 2000

41. Sparkes AH, Papasouliotis K, Sunvold G, et al: Bacterial flora in the duodenum of , healthy cats, and effect of dietary supplementation with fructooligosaccharides. Am J Vet Res 59:431--435, 1998 .

42. Sturman JA, Messing JM: High dietary taurine effects on feline tissue taurine concentrations and reproductive performance. J Nutr 122:82-88, 1992

43. Willard MD, Simpson RB, Cohen ND, et al: Effects of dietary fructooligosaccharide OJ'

selected bacterial populations in feces of dogs. Am J Vet Res 61:820- 825, 2000 44. Yajnik C: Interactions of perturbations in intrauterine growth and growth d lu'ing

childhood on the risk of adult-onset disease. Proc Nutr Soc 59:257- 265, 2000

Address reprint reques /:$ 1'0

Claudi.a A. Kirk, DVM, I hi ) Hill's Science and "[: hn logy Ill,' I'

Post I'n l30x I )fitl Top '1<0 , KS 6660 I- IWK


CONGENITAL AND INHERITED RENAL DISEASE OF

SMALL ANIMALS

Deborah S, Greco, DVM, PhD

Normal pediatric patients have immature kidneys, impaired renal function, and decreased renal blood flow and glomerular filtration rate until approximately 10 weeks of age.3 The immaturity of the kidneys leads to clinical implications in the treatment of pediatric veterinary patients, particularly when renal compromise is present. Pediatric patients are more susceptible to dehydration and overhydration. Similarly, drugs eliminated by or toxic to the kidneys should be used cautiously in pediatric patients.

Congenital renal diseases are present at birth and may be determined genetically; familial renal disorders occur in related animals with a higher frequency than would be expected by chance, and frequently are inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's syndrome), This article alerts the veterinarian to commonly observed congenital and hereditary conditions of the kidneys in small animals.

FUNCTIONAL ANOMALIES

Fanconi's Syndrome

Fanconi's syndrome, which results in impaired renal tubular reabsorp tion o f amil10 acids, glucose, and electrolytes, has been described in

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Basenjis, Norwegian Elkhounds, Schnauzers, and Shetland Sheepdogs.3

Clinical signs develop between 1 and 7 years of age, and are consistent with chronic renal failure . Urinalyses reveal glucosuria, mild proteinuria, and low urine specific gravity. Diagnosis is based on breed, clinical signs of polydipsia, polyuria, and laboratory abnormalities of normoglycemic glucosuria, aminoaciduria, nonanion gap metabolic acidosis, and hypo-kalemia.3

\

Cystinuria

Primarily a disorder of male dogs, including Irish and Scottish Terriers, cystinuria has been reported in over 60 breeds.3 There is a risk factor for the development of cysteine stones; however, most dogs show no clinical signs related to the disorder.

Hyperuricuria

Unlike cystinuria, hyperuricuria is associated with prediposition to urolithiasis in adulthood. The disease is transmitted as an autosomalrecessive disorder in Dalmations.3

Nephrogenic Diabetes Insipidus

This disease is described in puppies with severe polydipsia and polyuria, nocturia, and poor growth. Urine-specific gravity ranges from 1.002 to 1.005. Diagnosis is based on clinical signs and response to cautious water deprivation and antidiuretic hormone administration. ' Therapy consists of strategies to reduce the severity of polydipsia and polyuria, such as salt-restricted diets, and the diuretic chlorothiazide.

Primary Renal Glucosuria

Primary renal glucosuria has been reported in Scottish Terriers, Norwegian Elkhounds, and mixed-breed dogs.3 The dogs are asymptomatic. Diagnosis is based on persistent glucosuria in the face of eu lycemia.

STRUCTURAL ANOMALIES

Renal Agenesis

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CONGENITAL AND INHERITED RENAL DISEASE OF SMALL ANIMALS 395

because of compensatory hypertrophy of the contralateral kidney. This condition is familial in Beagles, Shetland Sheepdogs, and Doberman Pinschers. Clinical findings include an inability to detect both kidneys on palpation or radiography. This condition is often associated with agenesis of the ureter and abnormal or absent vas deferens, epididymus, or uterine horns. '

Renal Hypoplasia

Hypoplastic kidneys are composed of histologically normal nephrons; however, renal mass is reduced. Clinical findings and therapy depend on the extent of involvement with bilateral disease, carrying a much poorer prognosis.

Renal Dysplasia and Aplasia

Disorganized parenchyma and segmental or focal areas of immature or anomalous structures in an otherwise normal kidney characterize renal dysplasia. Renal aplasia refers to a more severe generalized form of dysplasia that affects the entire kidney. These conditions are observed in male and female puppies of many breeds (Table 1) and rarely in kittens. 1, 3-5, 8, 15 Puppies and kittens with renal dysplasia are often clinically normal for extended periods of time before signs of chronic renal failure ensue. The age of onset of clinical signs range from 4 weeks to 5 years; however, most are seen before 2 years of age.

Early subtle signs of chronic renal failure include selective appetite, poor growth and haircoat, weight loss, nocturia, and mild to moderate polydipsia and polyuria. Abdominal palpation may reveal small irregular kidneys and occasionally signs of rubber jaw, which is characterized by symmetric enlargement of the maxilla and mandible, bone pain, and soft pliable mandibles. Pathologic fractures also may be observed.

Laboratory findings characteristic of chronic renal failure include azotemia, hyperphosphatemia, metabolic acidosis, isosthenuria and normocytic, normochromic anemia. Renal secondary hyperparathyroidism may result in hypercalcemia or more commonly hypocalcemia. Low urine specific gravity, inactive sediment, and mild to moderate proteinuri.a are observed on the urinalysis. Diagnosis is based on signalment, lini.cal findings l and laboratory findings; however, renal biopsy is re

g II i I' 'd for d fjni. tiv diagnosis. Primary lesions of the kidneys include fv l;d g lo l11 ' 1'1I1i o r I'ubulc , persistent mesenchyme, persistent metanephric du elH, [I I I iell l lll blll Hr " pith 'Iiu m., and dysontogenetic metaplasia.3,5

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CONGENITAL AND lNHERITED RENAL DISEASE OF SMALL ANlMALS 397

adult dog or cat food in these patients. Phosphorus should be restricted by using a dietary phosphorus binder; the goal is to keep the serum phosphorus in the normal range.9 Calcitriol therapy (2-3 ng/kg per day) may be helpful in this regard; alternatively, calcium carbonate supplementation can be used. Finally, the use of angiotensin-converting enzyme inhibitors (dogs) and calcium channel blockers (cats) is suggested to ameliorate systemic hypertension.9 Metabolic acidosis can be addressed with oral bicarbonate therapy.9

Renal Ectopia and Fusion

Ectopia is the congenital malposition of one or both kidneys. Renal fusion is the congenital union of normally lateralized kidneys; fused kidneys may assume various shapes, such as horseshoe kidneys.

Duplex and Supernumerary Kidneys

Puppies may present with one or more accessory kidneys. If the supernumerary kidneys are affected by pyelonephritis, surgical resection is recommended.

Primary Renal Neoplasms

Several renal malignancies, including nephroblastoma, lymphosarcoma, carcinoma, and undifferentiated sarcoma, have been described in puppies and kittens, Surgery and chemotherapy may be recommended, although prognosis often is guarded in the case of nephroblastoma because of widespread metastasis. Hereditary multifocal renal cystadenocarcinomas have been reported in the German Shepherd dogP

Glomerulopathies

Proteinuric renal disease is the hallmark of glomerulopathies, in-I.udin congenital and inherited glomerulopathies. Congenital glomer

Ldopathi 'S h av b n describ d in the Samoyed, Bull Terrier, Doberman, IIng li l)h 0 I 'I" ~ GI,i I, Rollw 'iI I~ and Newfoundland.3, 5, 10-12, 16 Most I 1I1 I i(\ ' li nd I illl' nH w ilh l~ l ol\)('n J! (lF' t l i . tj I I" nt with signs of chronic I" 'nn l f:lillll'l' t'i illl('1' Iholll wi lli {)V(' I'I IIl' l hl"o li s ndl"om (peripheral (.\11' 1"01 , II 1>I'1'I ' 11\ )1" I,II 'I I ,I"lI illl , l ,r"" ,I IIII I'i I' , .\IHI h pon lhutni l111ri ).

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398 GRECO

dogs (X-linked). Affected dogs develop persistent proteinuria as early as 2 months of age and as late as 2 years of age. The affected male dogs may develop signs of chronic renal failure as puppies and may die at 8 to 16 months of age. Affected female dogs may have mild proteinuria in middle age. Urinalysis may reveal moderate to severe proteinuria and glucosuria or hematuria. Bull Terrier hereditary nephritis is a genetic disorder of Bull Terriers that is characterized by abnormalities of the glomerular basement membrane. It is similar histologically to the Samoyed glomerulopathy and is inherited as an autosomal dominant.

Doberman Pinscher familial glomerulonephritis is observed in puppies as young as 6 weeks, or may not become apparent until 8 years of age.16 Male dogs seem to be affected earlier than female dogs. Urinalyses reveal persistent marked proteinuria and, variably, glucosuria. Affected dogs also may have concurrent unilateral renal and ureteral aplasia. Diagnosis of hereditary glomerulopathies is based on signalment, clinical signs, and renal biopsy. Therapy for chronic renal failure, including dietary phosphorus restriction, control of systemic hypertension, and acidosis, may slow the rate of progression of disease.

Amyloidosis

Renal amyloidosis, the familial form, occurs in young related Abyssinian cats and. Chinese Shar Pei dogs.6, 7 The condition is recognized between 1 and 6 years of age. Clinical signs are those of chronic renal failure. Surprisingly, proteinuria is an inconsistent finding in affected animals. The medullary interstitium is the primary site of amyloid deposition in this disease, as opposed to the glomerulus in acquired renal amyloidosis. Diagnosis is based on breed, dinical signs, and renal biopsy.

Polycystic Renal Disease

This disorder is characterized by formation of multiple cysts throughout the renal medulla and cortex.2,14 Affected kidneys are enlarged and lobulated. Puppies and kittens of various breeds may be affected. A strong familial tendency occurs in Cairn Terriers, Persian cats, Beagles, and domestic long-haired cats. In Cairns, Persians, and domestic long-haired cats, hepatic biliary cysts also are observed. Cl ini· cal signs include progressive abdominal enlargement, renomega ly, 21 1 d signs of chronic renal failure . Diagnosis is based on r n al ultrasound and biopsy.

References

1. Aul"rnn (i(. MOI'1I 11l II ~; , ) ,111 11 11 ,,1,1 : d', 1,1 ,iI 11I 11'lil l,' 1I 'l lI iI .l 1I1I'II/H' II I 1'o01d" 11 ,, 'I I Ii 'v l ' l ll ')'w,''''' ' , '11 111 '11 ( 1'i1{,1 1'111 I ) 11\ 1\ 1 '1111 " II I " 'I" 1'I' It ,

CONGENITAL AND INHERITED RENAL DISEASE OF SMALL ANIMALS 399

2. Biller DS, Chew DJ, DiBartola SP: Polycystic kidney disease in a family of Persian cats. JAVMA 196:1288-1290, 1990

3. Bovee KC: Genetic and metabolic diseases of the kidney. In Bovee KC (ed): Canine Nephrology. Philadelphia, Harwell Publishing, 1984, pp 339-354

4. Brown CA, Crowell WA, Brown SA, et al: Suspected familial renal disease in Chow Chows. JAVMA 196:1279-1284, 1990

5. DiBartola SP: Familial renal disease in dogs and cats. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 5. Philadelphia, WB Saunders, 2000, pp 1698- 1703

6. DiBartola SP, Benson MD, Dwulet FE, et al: Isolation and characterization of amyloid protein AA in the Abyssinian cat. Lab Invest 52:485-489, 1985

7. DiBartola SP, Tarr MJ, Webb DM, et al: Familial renal amyloidosis in Chinese Shar Pei dogs. JAVMA 197:483-487, 1990

8. Eriksen K, Grondalen J: Familial renal disease in soft-coated Wheaten Terriers. J Small Anim Pract 25:489- 500, 1984

9. Finco DR, Brown SA, Barsanti JA, et al: Recent developments in the management of progressive renal failure. In Bonagura JD (ed): Kirk's Current Veterinary Therapy. Philadelphia, WB Saunders, 2000, pp 861-863

10. Hood Jc, Robinson WG, Huxtable CR, et al: Hereditary nephritis in the Bull Terrier: Evidence for inheritance by an autosomal dominant gene. Vet Rec 126:456-459, 1990

11. Jansen B, Valli VE, Throner P, et al: Samoyed hereditary glomerulopathy: Serial clinical and laboratory (urine, serum biochemistry, and hematology) studies. Can J Vet Res 51:387-391, 1987

12. Lees GE, Wilson PD, Helman RG, et al: Glomerular ultrastructural findings similar to hereditary nephritis in five English Cocker Spaniels. J Vet Intern Med 11:80-85, 1997

13. Lium B, Moe L: Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in the German Shepherd dog: Macroscopic and histopathologic changes. Vet Pathol 22:447-455, 1985

14. McAloose D, Casal M, Patterson DF, et al: Polycystic kidney and liver disease in two related West Highland White Terrier litters. Vet Pathol 35:77-81, 1998

15. Minkus G, Breuer W, Wanke R, et al: Familial nephropathy in Bernese Mountain dogs. Vet Pathol 31:421-428, 1994

16. Picut CA, Lewis RM: Juvenile renal disease in the Doberman Pinscher: Ultrastructural changes of the glomerular basement membrane. J Comp Pathol 97:587-596,1987


Deborah S. Greco, DVM, PhD Department of Clinical Sciences

College of Veterinary Medicine and Biological Sciences 300 W. Drake

Colorado State University Fort Collins, CO 80523-1601



DIAGNOSIS AND TREATMENT OF JUVENILE ENDOCRINE

DISORDERS IN PUPPIES AND KITTENS

Deborah S. Greco, DVM, PhD

Endocrine and metabolic disorders affecting puppies and kittens from birth until 6 months of age may manifest as clinical problems related to growth, water metabolism (polydipsia or polyuria), or as episodic weakness. Endocrine and metabolic disorders which affect stature, such as pituitary or hypothyroid dwarfism, present to the veterinarian for the assessment of delayed or aberrant growth. On the other hand, juvenile-onset diabetes mellitus and diabetes insipidus cause excessive thirst, urination, and difficulty in house-breaking.

PITUITARY DISORDERS

Central Diabetes Insipidus

Diabetes insipidus is a disorder of water metabolism characterized by polyuria, urine of low specific gravity or osmolality, and polydipsia.1•

17. 18 It is caused by defective secretion of antidiuretic hormone (i.e., central diabetes insipidus) or by the inability of the renal tubule to respond to antidiuretic hormone (i.e., nephrogenic diabetes insipidus) .1. 17. 18 Deficiency of antidiuretic hormone (vasopressin) can be partial or om.pl teo Central diabetes insipidus is characterized by an absolute or

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402 GRECO

relative lack of circulating antidiuretic hormone, and is classified as primary (idiopathic and congenital) or secondary. Secondary central diabetes insipidus usually results from head trauma or neoplasia. Central and nephrogenic diabetes insipidus are rare disorders.

Central diabetes insipidus may appear at any age, in any breed, and in either gender; however, young adults (6 months of age) most commonly are affected. The major clinical signs of diabetes insipidus are profound polyuria and polydipsia (more than 100 mL/kg per day; normal, 40 to 70 mL/kg per day), nocturia, and incontinence usually of several months' duration. The severity of the clinical signs varies because diabetes insipidus may result from a partial or complete defect in antidiuretic hormone secretion or action. Other less consistent signs are weight loss, because these animals are constantly seeking water, and dehydration.1, 12, 17, 18

Routine complete blood count (CBC), serum biochemical, and electrolyte profiles are usually normal in animals with diabetes insipidus. Plasma osmolality often will be high (> 310 mOsm/L) in central or nephrogenic diabetes insipidus because of dehydration. Puppies with primary polydipsia often will exhibit low plasma osmolality « 290 mOsm/L) because of overhydration. When abnormalities, such as slightly increased hematocrit or hypernatremia, are present on initial evaluation, they are usually secondary to dehydration from water restriction by the pet owner. In diabetes insipidus, the urinalysis is unremarkable except for the finding of a persistently dilute urine (urine specific gravity 1.004-1.012).1,17,18

Diagnostic tests to confirm and differentiate central diabetes insipidus, nephrogenic diabetes insipidus, and psychogenic polydipsia include the modified water deprivation test or response to antidiuretic hormone supplementation. The modified water deprivation test is designed to determine whether endogenous antidiuretic hormone is re- \ leased in response to dehydration and whether the kidneys can respond to antidiuretic hormone. The more common causes of polyuria and polydipsia should be ruled out before this procedure. Failure to recognize renal failure before water deprivation may lead to an incorrect or inconclusive diagnosis or may cause significant patient morbidity.I, 12. 17, II!

Pituitary Dwarfism

Pituitary dwarfism results from destruction of the pituitary gle nd by a neoplastic, degenerative, or anomalous process. It may basso int(·( I with decreased production of other pituitary hormon s, il III ling III roid-stimulating hormone (TSH), adreno orti o trOI i hor111 01')(' (/\(''1' 11 ), luteinizing hormone, Folli 1 - timul ating horm one, nnd !'I'OWlh I l( ) 1'1l 10 1 ll' .

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JUVENILE ENDOCRINE DISORDERS IN PUPPIES AND KITTENS 403

dwarfism are slow growth noticed in the first 2 to 3 months of life and mental retardation that usually is manifested as difficulty in housetraining.2 Physical examination findings m~y in~lude proportion~te dwarfism, retained puppy haircoat, hypotOnIC skm, trunkal alopeCla, cutaneous hyperpigmentation, infantile genitalia, and delayed dental eruption. Clinicopathologic features include eosinophilia, lYI?phocytosis, mild normocyctic normochromic anemia, hypophosphatemIa, and occasionally hypoglycemia resulting from secondary adrenal insufficiency.2 Differential diagnoses include other causes of stunted growth, such as hypothyroid dwarfism, portosystemic shunt, diabetes mellitus, hyperadrenocorticism, malnutrition, and parasitism. lO Diagnosis is made by measuring serum growth hormone concentrations (no longer commercially available) or serum somatomedin C (insulin-like growth factor 1).2 The advantage of insulin-like growth factor 1 is that it is not speciesspecific. There is a usually a subnormal response to exogenous TSH and ACTH stimulation tests; furthermore, endogenous TSH and ACTH are decreased in affected dogs because of panhypopituitarism.

PANCREATIC DISORDERS

Juvenile Diabetes Mellitus

Diabetes mellitus, a common endocrinopathy of adult dogs, rarely is observed in puppies. All reported cases of diabetes mellitus in dogs and cats have been type I or insulin-dependent diabetes mellitus.6 Many canine juvenile cases of diabetes mellitus, as in humans, are believed to have a viral cause. Dogs suffering from juvenile diabetes mellitus usually present between 3 and 6 months of age. A genetic basis for diabetes mellitus is suspected in the Keeshonden, and predisposed breeds for diabetes mellitus include Puliks, Cairn Terriers, miniature Pinschers, standard poodles, miniature schnauzers, dachshunds, and beagles.6

In young dogs and cats, stunted growth often is associated w.ith diabetes mellitus because of calorie deprivation. In dogs, progressIve polyuria, polydipsia, and weight loss develop rapidly usually over several weeks. Another presenting complaint of diabetes mellitus in puppies i acute onset of blindness caused by cataract formation. Diabetic cataracts can develop rapidly, and the owner may notice that the puppy suddenly i bumping into furniture and other obstacles. The most common phy i a.l examination findings are dehydration and muscle wasting or thin body ondition. l~ma i a t d di.abetic animals may have concurrent IlI1dl'rI ing li sol'(kl':-l, !-l li ch (IS ' xo rin' pancrea tic insufficiency, particu-1,, 1'1 Ilms\' wilh jll Vt' llil l' 1l1l1'I\'l di nbel t's.H /\ di agnos is of diabetes mellitus /: h()lIld hi ' "il li l,d ,H I 1111 ' 111 \' 11'1)(,1' nll 'li"iI'ill Higns coml , li bl ' with di be-11'11 11 11'111111, , 11111 I'V1 1l " II I'I ' il l lil ld111)', II Yl lI' l')',IYi 'I ' IlILI IIIH I ).J \'iI, lll'i n,

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subcutaneously (SQ) twice daily. The puppies must be fed 3 to 4 times daily, and regular insulin must be administered at a dose of 0.1 to 0.2 U /kg SQ with meals. A growth formulation, rather than high-fiber foods, should be fed to growing puppies and kittens. Caloric requirements should be calculated for a growing animal.

THYROID DISORDERS

Congenital Hypothyroidism

Congenital hypothyroidism is a common endocrine disorder in hum~n. infa.ntsP In contrast, there are few reports of congenital hypothyrOIdIsm m dogs and cats.4, 10, 14, 15,20 Only 3,6% of the cases of canine hypothyro~d~sm occur in dogs younger than 1 year of age,15 Congenital hypothyrOIdIsm may be caused by aplasia or hypoplasia of the thyroid /?iland, thyroid ectopia, dyshormonogenesis, maternal goitrogen ingestion, maternal radoactive iodine treahnent, iodine deficiency (endemic goi~e~), autoimmune t~yro.iditis, hypopituitarism, isolated thyrotropin defICIency, hypothalamIc dIsease, or Isolated thyrotropin releasing hormone (TRH) deficiency, 9

Because thyroid hormone secretion is essential for normal postnatal de.v:lop~ent of the .nervous ~nd skeletal systems, congenital hypothyr~)ldiSm IS charactenzed by dIsproportionate dwarfism, central and penpheral nervous system abnormalities, and mental deficiency.13 Signs of adult-onset hypothyroidism, such as lethargy, inappetence, constipation, dermatopathy, and hypothermia, also may be observed.

Congenital hypothyroidism, regardless of cause, has characteristic historical and physical examination features, Dogs and infants have a histo~y of large birth weight (in babies, a result of prolonged gestation) t~at IS followed by aberrant and delayed growthP In puppies, the first \ SIgnS of abnormal growth occur as early as 3 weeks after birth, and a!='n?rmal body p~oportions are evident by 8 weeks of age- which is sIm~l~r to huma~ n:fa~ts, which are normal at birth but, if undiagnosed, ~xhibit charactenstIc SIgnS by 6 to 8 weeks of ageP Historical finding m puppies with hypothyroidism, such as lethargy, mental dullness, wea k nursing, delayed dental eruption, and abdominal distention, a1 0 ar observed in children with hypothyroidism.13

. Physic~~ features. of hJ:'pothyr~id dwarfism in children include hypotoma, umbIlical herma, skm mottlmg, large anterior and po t ri r fontanels, macroglossia, hoarse cry, distended abdomen, dry skin, joun.li " pallor, slow deep tendon reflex, delayed dental eruption, and hYI o thermia?' 11, 13, 21 In dogs with congenital hypothyroidism, hypotoniCl , I1l nc ro~

glossia, distended abdomen, dry skin, delay d d ntal ' 1"1'1 lion, .111(1 hypothermia have been d s rib d (Fig, '1 on I 2).,1, (', II, 'I, II 1" , " II 1$ '1' :11 1111"

dogs develop mor r;:q idly nn I be('OII; <' w{' ighl bl'n ril1)', '$(111( '1' Ih ,lll 111.11nan infants, g;dl Ilhl101'Ill :liil i(" .lIlt! di :4 prOI 1( 1I 'll(llloll, ' d W.1 I'll: III 111 '1' pr()l~li ll('nl f(', lIIII 'I't III 1'111"111" 1'()II) ', I'IilI.Ji hYllillll Vl'll ld 11 111 MtdJ.II 'I, II VIIII 1'1,1 11 111 , II hl'llll1l 111 1111' , Iliitl II III }',I' 1'11 1111111111 )', 1(111 )', 111 ' 111 1' Plll l' " I 11'1'


Figure 1. Standard Schnauzer littermates demonstrating differences in physique between euthyroid (right) and congenitally hypothyroid (left) puppies.

sequelae of untreated hypothyroidism in humans.13 Similar facial features, such as broad maxillas and macroglossia, have been observed in affected puppies. In humans, delayed eruption of permanent teeth is observed in untreated individuals with congenital hypothyroidism; delayed dental eruption is characteristic of puppies with hypothyroidism diagnosed after 4 months of age. In humans and in dogs, macroglossia and effusions of the body cavities are the result of myxedematous fluid

406 GRECO

accumulation.9, 13 Puppies with hypothyroidism often exhibit haircoat abnormalities, including retention of the puppy haircoat and thinning.

Thyroid hormone is crucial for proper postnatal development of the nervous system. Infants with untreated hypothyroidism exhibit poor coordination and speech impediments later in life.16 Delayed treatment often results in low perceptual-motor, visual- spatial, and language scores in children with congenital hypothyroidism. If treatment is delayed beyond 4 to 6 months in human babies, intelligence irreversibly is affected, and mental retardation may ensue. Mental retardation is also likely in puppies with hypothyroidism; however, no objective evidence of delayed or aberrant intelligence is available to assess affected puppies. Because the bulk of cerebellar development occurs postnatally, Purkinje cell growth also is affected significantly by congenital hypothyroidism.19

In humans and puppies, if treatment is delayed, signs of cerebellar dysfunction, such as ataxia, are observed.9, 19

Skeletal abnormalities, such as delayed maturation and epiphyseal dysgenesis, are the hallmark of congenital hypothyroidism.23 Delayed epiphyseal maturation is observed in the vertebral bodies and long bones of affected puppies. Epiphyseal dysgenesis, which is characterized by a ragged epiphysis with scattered foci of calcification, is observed in humans and dogs with untreated congenital hypothyroidism (Fig. 3A and B) . Normal epiphyseal development proceeds from a single center; however, in hypothyroidism, thyroid deficiency leads the development of multiple epiphyseal centers, each with its own calcification progression. Disorderly epiphyseal calcification leads to secondary ar thropathies in children suffering from untreated congenital hypothyroidism. 23

Clinicopathologic features of congenital hypothyroidism include hypercholesterolemia, hypercalcemia, and mild anemia. Hypercholesterolemia develops in congenital and adult-onset hypothyroidism because of decreased hepatic metabolism and decreased fecal excretion of choles- ' terol. Hypercalcemia secondary to congenital hypothyroidism is the result of decreased renal clearance and increased gastrointestinal absorption of calcium.22 Decreased thyroid hormone stimulation of erythropoietic precursors results in a mild normocytic, normochromic anemia in some puppies suffering from hypothyroidism.s

Thyroxine is essential for the proper transcription, translation, and secretion of growth hormone by pituitary somatotrophs.24 In humans (and most likely the dog), circulating growth hormone concentra ti o n ~ are high during the first few days after birth, but rapidly decrease during the subsequent few weeks to levels just slightly above tho in ad I Ii ts. In a previously reported case of congenital hypothyroid i 111 , th ' dog exhibited a blunted growth hormone response to xyla7. in , but hnd n normal growth hormone response to provoca tiv s til11ul , li ot, nfl'{'r Irl-I II ment of the hypothyroid sta teYI

Diagnosi of ongl-nil . I h polh J'o idi ,' 111 L' hd Nt-d (I ll 1'lillie,1I /11) ;1\: " upporting clinicnl I .Ilho lo)" y ,lI ld II I I'lli d 11111t 'lio ll It':IIIII )'" Ntll'lll .d Pili '

pi t'. ' '))',l'tl !) 10 (I WI'I,I :I I' ,! \' t' :1\' 11111 1 11l1.t! 11 1\' " 1 II I" CII'I ) l'IIII I'I'IIII'dll llll ' IWII II I 1111'1'1' 1111 11'1 I tI ),, 1Ii ' l 111 11 11 111 111 11 11 1 ,1, llil l til l)', I. 1111 ' 11 '111 11 ', Ii .1' 11 1111


Figure 3. A and B, Differences in long bone growth plates between littermates in Figure 1. Note the delayed progression of closure of growth plates and shortened radius and ulna in the affected puppy.

TT4 of 2.0 fLg/ dL, which is normal for an adult dog, would be low in a 6-week-old puppy and indicative of thyroid dysfunction. Serum-free thyroxine (FT4) also would be expected to be higher in neonatal dogs. Indeed, . a recent report of TT4, FT4, total triiodothyronine (TT3), free triiodothyronine (FT3), and reverse T3 (rT3) in puppies from birth to 12 weeks confirmed the suspicion that TT4 and FT4 are high in neonates.3

At birth, TT4 was within the normal range; but by 1 week of age and until 5 w eeks of age, the serum TT4 was two to three times the normal adult range, TT3 and FT3 were lower in these neonatal puppies, suggesting an inability of neonatal animals to convert T4 to T3 peripherally. The adven t of the endogenous canine TSH assay should allow discrimination of prim.ary congenital hypothyroidism from secondary hypothyr i li sm (T H d fid ncy). Puppies with primary hypothyroidism (e.g., ('hy roid 1ysg 11 -s is, dyshonrtonogen sis) would be expected to have (' lvv;) I( 'd enti ogl-l1lHl ' '['SII on -nl r::tl ions, whet: a puppies with TSH d '(ki "Il ' , hOlild buv(' , IlilIH )I 'IIl HI I'ndo)',t'l OilS T. li on ntrations. Spe\'In" il llId j, 'n 11 11 ,'I\l lol',I'IH 111 11 ' \,~; II 111 II (lOlldl" l'l1 n itw,' I nvC' nOl" h n 111 '1'111 1'1111 ' i I

'1''' '1 11'' 11" 111 II I 111 11 ),," 1\ l,tI 11 1' 1,,,1111' 1111" '111 11 III 111 1[ '1' " /I ,1111 1 I, 111 " ll il ill 1111 hll 111111 '1 1111 1, '111 Iii 11 11 ' l"l til 1111 II lt tl ( I I II 111-.1 1, )', 'I IIII' tl lI )\ III'" II

408 GRECO

Figure 4. Normalization of physique after supplementation of L-thyroxine in the congenitally hypothyroid puppy from Figure 1.

f.Lg/kg once daily in the cat). Early treatment results in normalization of the physique (Fig. 4).

References

1. Bruyette DS: Polyuria and polydipsia. In August JR (ed): Consultations in Feline Internal Medicine. Philadelphia, WB Saunders, 1991, p 227

2. Campbell KL: Growth hormone-related disorders in dogs. Compend Contin Educ Pract Vet 10:477-482, 1998

3. Casal ML, Zerbe CA, Jezyk PF, et al: Thyroid profiles in healthy puppies from birth to 12 weeks of age. Proc Am Coli Vet Intern Med, San Francisco, CA, 1994, P 989

4. Chastain CB, McNeil SV, Graham CL, et al: Congenital hypothyroidism in a dog due to an iodide organification defect. Am J Vet Res 44:1257- 1265, 1983

5. Cline MJ, Berlin NI: Erythropoesis and red cell survivial in the hypothyroid clog. 1\111 J Physiol 204:415-418, 1963

6. Feldman EC, Nelson RW: Canine and Feline Endocr in.ology and R>procl u lion, cd. I. Philadelphia, WB Saunders, 1987, pp 55- 90

7. Fisher DA: Medical management of sllspect d aSCH of l'OI1)\I 'lIi I'll I Ii I (l lh roi d l 111 , 11/ Burrow GN (ed) : Neona t@l Thyro"icl S p 'ning. NI'w (11'1, 1{.lVI' 1I l' I"'IiH, 19BO, pp 2:1'1 244

8. Greco DS, h iJ~tn i n CH: I ':n(l 1)(' 1'1 1)1' diHOI'd,'! 'H, II/ 11 ' 11 11, 111 11 II ) (, ·d): V,' I", 'I," " Y I'"dllll , I, tl,

d . 2, Phil acl \' lphi ll , W II :;, 11 11 11 1,'1'11, 11)%, 1'1' \'1'/ 111'/


9. Greco DS, Feldman EC, Peterson ME, et al: Congenital hypothyroid dwarfism in a family of Giant Schnauzers. J Vet Intern Med 5:57-65, 1991

10. Greco DS, Peterson ME, Cho DY: Juvenile-onset hypothyroidism in a dog. J Am Vet Med Assoc 187:948-950,1985

11. Kenny FM, Klein AH, Augustin AV, et al: Sporadic cretinism. In Fisher DA, Gurrow GN (eds): Perinatal Thyroid Physiology and Disease. New York, Raven Press, 1975 pp 73- 78

12. Krause KH: The use of desmopressin in diagnosis and treatment of diabetes inSipidus in cats. Compend Contin Educ Pract Vet 9:752, 1987

13. LaFranchi SH: Hypothyroidism. Pediatr Clin North Am 26:33- 51, 1979 14. Medleau L, Eigenmann JE, Saunders HM, et al: Congenital hypothyroidism in a dog.

J Am Anim Hosp Assoc 21:341- 343, 1985 15. Milne KL, Hayes HM: Epidemiologic features of canine hypothyroidism. Cornell Vet

71:3-14,1981 16. Moschini L, Costa P, Marinelli E, et al: Longitudinal assessment of children with

congenital hypothyroidism detected by neonatal screening. Helv Paediatr Acta 41:415-424,1986

17. Nichols CE: Endocrine and metabolic causes of polyuria and polydipsia. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy XI. Philadelphia, WB Saunders, 1992, p 293

18. Nichols R: Diabetes insipidus. In Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders, 1989, p 973

19. Noguchi T, Sugisaki T: Hypomyelination in the cerebrum of the congenitally hypothyroid mouse (hyt). J Neurochem 42:891-893, 1984

20. Robinson WF, Shaw SE, Stanley B, et al: Congenital hypothyroidism in Scottish Deerhound puppies. Aust Vet J 65:386-389, 1988

21. Sawin CT: Hypothyroidism. Med Clin North Am 69:989-1004,1985 22. Tau C, Garagedian M, Farriaux JP, et al: Hypercalcemia in infants with congenital

hypothyroidism and its relation to vitamin D and thyroid hormones. J Pediatr 109:808-814, 1986

23. Wilkins L: Epiphyseal dysgenesis associated with hypothyroidism. Am J Dis Child 61:13- 34, 1941

24. Wood DF, Franklyn JA, Docherty K: The effect of thyroid hormones on a growth hormone gene expression in vivo in rats. J Endocrinol 112:459-463, 1987


Deborah S. Greco, DVM, PhD Department of Clinical Sciences

College of Veterinary Medicine and Biological Sciences 300 W. Drake

Colorado State University Fort Collins, CO 80523-1601



FRUSTRATING CASE PRESENTATIONS IN CANINE

THERIOGENOLOGY

Autumn P. Davidson, DVM

Generally, small animal theriogenology is a rewarding subspecialty in veterinary medicine. Although demanding of the clinician's time and expertise, the breeder client tends to be loyal and compliant. A good reproductive practice generates its own referrals, and usually is busy. Obstetrics and pediatrics are undeniably rewarding parts of the specialty. Theriogenology incorporates the interesting fields of reproductive physiology, endocrinology, embryology, genetics, metabolism, nutrition, critical care, anesthesia, pharmacology, and anatomy. The theriogenologist's practice is uniquely medical and surgical.

Frustrations do exist in the small animal theriogenologist's practice. Technology in the small animal theriogenology practice has not kept pace with that in the equine or bovine field and even less so with the practice of human reproduction. The primary reason is a lack of funding supporting the development of technical expertise in a field in which anticipated financial returns are poor. The Westminster Kennel Club Best of Breed stud dog will never match the financial expectations of the Triple Crown winner. The value of such dogs (and cats) is more personal, but even the most motivated dog or cat owner cannot afford to develop a technique permitting intracytoplasmic insemination or embryo transplant in his or her pet. Technology developed for equine and bovine patients may not be applicable or effective in the canine or feline. Reli able induction of fertile estrus in the bitch remains technically chal-

iI'·( lm lIw I k pn,·I I1ll'n IH or ML'cii in!; nnd Epid 'll1iology, School of Veterinary Medicine, l!lll v,·,·sll y or '" l lromi.., I I . v i ~; .I nti 1111' Vel 'rinary linic, Guide Dogs for the Blind, II 11'., ~:I '" 1, " 1 .... 1, ( " rl lI,\I • !i ,l

V II' II 'IWJ Il (11 tJ II ', III' I Jt il ' lll \[\ 11 ·1'1\ '1[\ 1 II N I1v\ 1\ 1 I ' I{I\ ( 1'1('1'

\ I II I I ~ \I I I · t 11 I ~ I I II I • ~ I I ' I I 'I Ii I I III

412 DAVIDSON

lenging. Male subfertility in the stud dog has few options. Pediatric critical care in canine and feline practice is exacerbated by small patient size and financial constraints.

Fortunately, the development of advanced reproductive technology in endangered canine and feline species may apply to dogs and cats. The ~atural fecun~ity of dogs and ~ats and the consequent pet overpopulation problem Inject further ethIcal concerns into the small animal theriogenologist's practice. Clinicians should guide their clients through the myriad genetic screenings advised for the particular breed, and shoul~ discuss proper puppy placement and neutering. Some dogs and cats sImply should not be bred (aggressive or genetically defective individuals), despite their inherent value to the client.s Unsolved and controversial clinical problems are not uncommon to the reproductive practitioner. Progress in understanding the cause, pathophysiology, and proper therapeutics of such problems is hampered by anecdotal information abounding among the breeder clientele and often among veterinarians. University residencies and postdoctorate programs limited to OL

even emphasizing small animal theriogenology are uncommon. Collaborat~on a~ong small animal theriogenologists is developing slowly. This article dIscusses some of the clinical problems familiar to the small animal reproduction specialist.

PUPPY VAGINITIS

Chief Complaint

An apparently healthy female puppy presents with mucoid vulvar discharge, usually white to yellow and sometimes copious. The dis~harge c~ be accompanied by mild perivulvar dermatitis. The puppy ' IS not typIcally attentive to the discharge, and there is not. any associated change in urinary behavior. The age of onset ranges from 6 weeks to puberty, the duration is days to months, and the disorder is often intermi ttent.

Diagnostics

Cytologic examination of the discharge finds suppurative inflammation. Vagi~al cultures .(aerobic) generally fail to grow anything but normal flora In small, mIxed numbers. A urinalysis (culture "if"), a -quired by cystocentesis, is characteristically normal (a decrea durin specific gravity is typical for pediatric dogs).

Cause

The p . ifi il lL '(' iii 111l111 !1 WI) , 1\ 11 illil lltl llllll ' Iii /lI VI'IIIII ' li d) ', ll ld gland lll nr (· pIlIH ·lllIlll hli li 11I 11'Il llI ll llil lll Jld 1III III ' IIII 'lIdllll ', III, ' "1111.11 11111

FRUSTRATING CASE PRESENTATIONS IN CANINE THERIOGENOLOGY 413

is reported to resolve with puberty or ovariohysterectomy (two different events endocrinologic ally, neither likely to be truly therapeutic). Puppy vaginitis diminishes with maturity in most cases. Important differentials include urinary tract infection, urinary incontinence, the onset of the initial estrous cycle, vaginal foreign bodies (i.e., foxtails), and vaginal anatomic anomalies causing pooling of urine or secretions.2

Therapeutics

Cleansing the perivulvar area with a gentle solution (nonalcoholic otic preparations or baby wipes) and benign neglect are advised if other maladies are not evident.

CHRONIC VAGINITIS

Chief Complaint

The dog presents with variable vulvar discharge that is mucoid to hemorrhagic or purulent, which is accompanied by signs of discomfort (e.g., licking, scooting, pollakiuria). Perivulvar dermatitis also may be present.n The condition usually is noted in ovariectomized bitches, of any age, and in variable times from the spay procedure. The history usually includes multiple therapeutic efforts without resolution, although transient improvement can occur. The duration is generally chronic, from weeks to months and sometimes years.

Diagnostics

A minimum data base (complete blood count [CBC] and serum chemistries), including a urinalysis (preferably acquired by cystocentesis) and culture or culture "if," is advised. A careful perivulvar and vaginal examination, preferably with the dog under sedation or anesthesia, with endoscopic equipment allowing evaluation of the entire vaginal vault, should be performed. Radiography (e.g., vaginogram, urethrogram, cystogram, intravenous pyelogram [IVPl) and ultrasound of the lower genitourinary tract may be indicated. Vaginal cytology, aerobic ondmy opla ma cranial guarded vaginal cultures, and pinch biopsy of (Iff ted vaginal mucosa are helpful. Identification of any contributory (1 \1 , torn ic nb norrn a liti s iimportant (e.g., significant strictures, mass ivli i()I1S, rvtiunliant lors'" I vLdvar fold, pelvic bladder, anomalous ure-1III'il i 11 111i1 III1) y), II is h \11 (ul to v;) luntc I'll bitch in a normal standing IH II 1IIll11 Itl II/ It'HI ,\\ 1, '1'11 ,11 Il l1 l1 tOIll fll ' (, lI I'll Ivl nnd to I' peat the exami-11 ,11 1(1 11 11 111 '1' I I II' 11.11 11 1'i 11 .II I,d ,'Illi .I )'"ti ll ti'1t'1'1'1'('111111)('n . Th PI' n e Iii 1111111 ' 1"lIdlll )'1 III 1111' V 1)',1 11 d vi lldl , 11I111 ,1i WIIl '11 IIII' hil t' h i. ' lInti l' 1'

dll ,11 1I 111'11I1 1 ' 111\ II" Ild fl l,'j\d II )'., 111111 11 \1 ' 1111 ' (\ 111 '1' II I 1'I·dlll\1I 11111 vll lv,I I'

414 DAVIDSON

folds can be difficult to ascertain when the bitch is positioned for vaginoscopy.

Cause

The cause of chronic vaginitis is usually multifactorial, and the primary cause often is masked and exacerbated by previous therapies, including long-term antimicrobial use, self-mutilation, and topical irrigations. Vaginal mucosal biopsy frequently shows lymphoplasmacytic inflammation, but sometimes suppurative (neutrophilic) or eosinophilic inflammation is predominant. Cranial vaginal cultures can show overgrowth of an atypical bacterial species (pure gram-negative cultures, resistant organisms, Pseudomonas species) or pure culture of Mycoplasma species if antibiotics have been used extensively. Occasionally, a yeast (Malessezia) overgrowth is identified. Extensive perivulvar dermatitis can perpetuate chronic vaginitis. Urinary tract infection with urethritis and cystitis also can contribute to vaginitis. Vaginal foreign bodies and neoplasia can cause symptoms of chronic vaginitis.2

Therapeutics

The discontinuation of topical irrigations, prevention of self-mutilation with Elizabethan collars, and initiation of antimicrobial therapy only when indicated by proper interpretation of culture and sensitivity testing should be undertaken. Antimicrobial therapy should be limited , to those cases in which pathogens have been identified as displacing normal flora. Topical estrogen therapy is helpful in establishing normal mucosal integrity in postmenopausal women with idiopathic vaginitis; oral diethylstilbesterol therapy can be evaluated in the ovariectomized bitch. The dose is empiric and usually the same as used for urinary incontinence caused by sphincter incompetence (0.5- 1.0 mg orally given one to two times weekly). Several weeks of therapy with estrogen may be required before improvement is recognized. A short anti-inflammatory course of corticosteroids can be useful in diminishing vaginal pathology, but the subsequent propensity for urinary tract in f ction m Li st be kept in mind. Nonsteroidal anti-inflammatories may be us f Lil. urg i-

, cal correction with careful postoperative control of If-Illuti la tion iH indicated if anatomic abnormalities have contributed to Or hilv ' Ca liI' ,d the condition.6 Redundant dorsal vulvar folds a r mol" om lll oni inlpli cated than vaginal strictures. Obviotl 'Iy, 1"1 (' id <'nl i(i cnli (l /1 ,1I 1d l'< 'lll (lv: li of foreign bodies bOll ld cll re v<"Igini tis. ;\ 1"'1 ro Jl!'!' II I' 1111'1'1 '1 II/' id l·lll in l·d vaginal neop lms i" ('<"In inc ll l( ie H11I'g 'I' Ill' l'I" 'II)(l lh l' I'I IP ,II


SHORTENED INTERESTROUS INTERVAL

Chief Complaint

A bitch exhibiting failure to conceive is found to have interestrous intervals of less than 4 months.

DiagnostiCS

Evaluation of the bitch's entire estrous cycle finds it to be normal in all aspects except a shortened interestrous interval. Ovulation is confirmed with measurement of serum progesterone levels, and is preceded by a normal elevation of serum estrogen as documented by serial vaginal cytologies. Estrous behavior is normal. No evidence of systemic disease is present. The interval from onset of proestrus between cycles is less than 4 months. This shortened interval is documented to be caused by an abbreviated anestrus or diestrus as opposed to a failure of ovulation and subsequent lack of diestrus. Diestrus may not last the expected average 45-day interval. Ultrasonography of the reproductive tract fails to demonstrate any abnormalities.

Cause

The cause is unknown, but it is suspected to have a familial tendency, because the condition is seen more commonly in certain breeds (Rottweiler, Bull Mastiff, Mastiff). Exogenous inhibition of prolactin secretion by the administration of dopamine agonists can shorten the interestrous interval in bitches. The status of prolactin secretion (or presence of undefined dopamine agonism) in bitches with spontaneously abbreviated interestrous intervals is unknown. Infertility results, presumably caused by a failure of adequate involution of the uterus during the abbreviated anestrus.

Therapeutics

Inhibiting cycling for a milllmum of 6 months is advocated as effective management of this condition. To benefit from the rest period, br 'd lllg shou ld take place on the subsequent estrous cycle. Inhibition of 'ycl ing n lll be CI com lioh '0 by n ative feedback. Unfortunately, the ()Ill drll ); li l'VII , l'ti (or /i ud l 11 1'(' is A ~ rog 's t rone compound, and it is ('Old " 111111 1"0111 '.1 ill 11\1 ' 11I !. I, '1 hill' h ni\( l I.PIVl' 11 lK'ca liS' of its orrelation wll h 11)(' iI ,' 1,101'1I1I' liI Iii IIYI)llIi' II'Ii . 'I'h.' I I/h' or Idlll'li{' Ll nd rog 'ni 1"III'I I()l lI l!ir (11 111111,'1'11111 ', ( '1''''1111 ' III I II ) 1\ 111'1 1\11 1 v,' 1'1101"(0 i'or III 'n'Nli lll) "YI 'III ' lI y, 1VI II\lI III 11)1 ' Ilrl hil i 11111 11 11' 1111 11 11 ' " 0',,.,111111 11 1'11 1 I" I'YII II II ' II'I1 , ' /\ ' \1 '1 ""I ,iI " '1'"1 1'1 "I dl,'liI 111 ', iI • \. 1 •• , 111111 iil l' l ll ld \, . 1111 11 1', 11 \1' III II

416 DAVIDSON

estrous cycle after cessation of the compound, presumably caused by uterine atrophy, are common. Waiting for a more fertile estrous cycle to occur may allow frequent cycling to become re-establis~ed. No controlled studies have been performed that evaluate the efficacy of. such an approach. The manufacturer specifically states that the drug is not intended for use in bitches intended for breeding.

PREMATURE LABOR

Chief Complaint

Healthy bitches sometimes exhibit a failure to carry litters to term with no infectious or septic cause of the premature delivery apparent. Premature neonates have a poor prognosis for survival.

Cause

Commonly, measured progesterone levels at the time of premature delivery are low « 5 ng/mL), suggesting hypoluteoidi~m, or p~emature luteolysis. Hypoluteoidism has not been documented m the bitch as a primary cause for late-term aborti~n . Progesteror:e levels probably decline because of local prostaglandm release, which occurs because of myometrial activity.4

Diagnostics

If intervention does not occur, late gestational hemorrhagic vulvar discharge can occur, followed by the appearance of uteroverdin and eventually the delivery of premature, nonviabl~ neona~es. Prel!,-at~lr labor can be documented in the bitch by performmg utenne momtonng during the last 2 to 3 weeks of gestation with a co~erci~lly available uterine monitor. Monitoring can be performed by chents m the hom\.! setting. No more than one or two contractions should occur during a 1-hour monitoring session before stage I labor is appropriate (56- 1::8 dnys from the diestral shift or 64-66 days from the luteinizing bormOIll' SlII');V

or initial rise in progesterone above baseline). Monitoring should Inll' place twice daily during the last 10 to !4 day of g's tnliol . l' l·t'v il)l!. examination of the aborted fetu sand blt h should he vt' nli('d (J Ill 011\ infectious (e.g., brullosis) or se ll'i (' .g., I Inc(,ll lili s, IlWII'ill l-l) ('1 1\1 /11, 1\11 early d li v ry, nnt! Ihl' ,d)()rl('d (l' III ,'('S , illlllid hol v!' \)( '('1\ 1\111'11\111 111\ pos l'morl(,lIl (' IlIlliJl,d i(1 11 \11111'1' 1111111 Ih,jl\)', illllll llllll'I' W Ih 111, ,11'1 lill i/


Therapeutics

The administration of exogenous progestational compounds can prolong gestation in the normal bitch, but will not alleviate premature myometrial activity adequately. Their administration can cause abnormal differentiation of fetal gonads. The administration of tocolytic compounds (e.g., terbutaline, Brethine) by subcutaneous or oral route, titrated to effect, can inhibit premature uterine activity. Terbutaline is a tocolytic agent, a l3-adrenergic receptor antagonist. The administration; should be discontinued 48 hours before the calculated delivery date to permit normal labor and delivery to occur.

ACQUIRED MALE SUBFERTILITY

Chief Complaint

An apparently healthy, young, formerly fertile stud dog with normal libido begins to produce small litters or frequently fails to cover bitches.

Diagnostics

Ideally, the breeding behavior of the dog should be witnessed to rule out problems with husbandry. Documentation of failure to cover a known fertile bitch when bred appropriately is desirable. Failure to achieve a normal copulatory lock because of poor breeding habits (most commonly, a dog that attempts to turn before complete engorgement of the bulbis has occurred) can cause poor breeding success. If breeding behavior is normal, a complete physical examination, CBC, serum chemistries, Brucella screening, urinalysis with culture (sample acquired by cystocentesis), semen evaluation with appropriate quantitative urethral and ejaculate cultures, and ultrasound evaluation of the reproductive organs should be performed to rule out infectious, septic, and metabolic causes of acquired sub fertility. Assessment of the thyroid status alleviates client concerns (total T4, free T4 by equilibrium dialysis, thyroglobulin autoantibodies, and canine endogenous TSH [thyrotropin]), but is an unlikely cause of infertility.s Semen cytology typically finds oligospermia, a thenospermia, and sperm morphologic abnormalities. Epithelial

' Il ' and l1'l.onocytes are increased in the ejaculate. Sperm-to-sperm agg lulina ti on may be evident. Multiple semen evaluations over a 90- to 120-dny I ' rind should be performed to be valid. Azoospermia should prompl evn lu <lliol1 of s 'm 'n nil nlin ' pho phatase levels to assess libido .1 1111 1'I1i(' (11 11 hil .i\vnd nbs ln l(' li Vl' di sOI'lkrs . 1: ticular biopsy can be IH'l'llll 'lIH ,d III 1'h.II ' 1. 'II' I·j/,,(, ,1( 11 'I\II ,1('Y 0111(\ 1'0 1111 I('\'en 'Sf> of pennatogene-

I il iid 1111 ' IIlIoIl '1 I 11 '1 ' t il 'I III ' 111 "I" 'IIII ,iln)', I'lli l' "JlP,lrnllls. liltLir of the 1111j1/1 \' \1\ '1 1111 '11 11111 Il\' " .. ll dll l II 11'111;'11 1111t! 11I '1' IIIml (, lIiIIlI'VS hnv(' 1"'1'11 dlll l; 1"1 111 1111; '11 '11'1 til 11 0111 ' 11 11 11 11 '1'11 1" 'illIllIlI'd , Ii IWIIII 'rill )', iH

418 DAVIDSON

elected, the complete testicles should be submitted for histopathologic evaluation, permitting the breeder to document the cause for planning future breedings with related individuals.?

Cause

Generally, no infectious, endocrinologic, or metabolic cause for the acquired sub fertility can be identified. Testicular biopsy can identify lymphoplasmacytic inflammation if performed early. in the co';lrse. of disease. The measurement of or assessment for antisperm antibodIes would be of interest. The cause of this inflammation is unknown; previous traumatic or infectious causes generally are not identified. BioRsy late in the course of the disorder shows no evidence of inflammation; instead diminished spermatogenesis and atrophy are evident. A familial tendency is suspected in some breeds (Bull Mastiff, Bernese Mountain dog).9

Therapeutics

The diagnosis of premature testicular degeneration warrants a poor prognosis for return to normal fertility. Assisted reproductive techniques, such as intrauterine insemination, optimal ovulation timing, and semen banking, can improve pregnancy rates for a limited time. Clients should be warned of the potential heritability of this problem. The use of immunosuppressive agents is contraindicated because of their effect on spermatogenesis.

IDIOPATHIC AGALACTIA

Chief Complaint

A postpartum otherwise healthy bitch presents with inadequate lactation to meet neonatal demand. Normal gestational length and husbandry are typical.

Diagnostics

Determination that adequate mammary development and la ta tion have occurred should take place before an elective c a r an s(' tion. If an emergency section is required, regardles of th s tatuH of In 'Inlio l1, intervention is indicated. Bitch with inadc'l'.-IAte Id cl ;llioll ,II 1('I'Il) should be evaluat d thol'OlI )'hly for 111c1'n bo lic ()I" ill(l:lllll1l.lIlIl' !iil ol'll l'I'r (e.g., In triti s, ,('1<1 1\\\1, i,l , Ill il , lil i.) ;111(\ Ilul l'i li' )II,l1 ,1 1)(1 II (\1 '.1 11, 111 lil llIl lI l, nnd ,' holdd Iw In',lkd .l1' IH 'Il III 'I. II, '1 , (). 'I'11i1 1111 \1 '/ \ II \, IY 111'1111111 I'V II I\II lillil (I I 111i ' hl'l\lll) ',I'11I1I 1" 111\ 11 l'hl '"11 1111 ' I, 11111 1 \1( 1) ',1 111" "111'hlll l'l'" lI ild

FRUSTRATIN AS E PRESENTATIONS IN CANINE THERIOGENOLOGY 419

ultrasound evaluation of the uterus. The normal presence of colostrum (typically not copious) should not be confused with agalactia. The level of neonatal contentment and weight gain indicate adequate lactation and nursing.

Cause

Lactation results from proper integration of mammary parenchymal and glandular development during gestation, and is under the control of pituitary and ovarian hormones (i.e., proclatin, estrogen). Milk letdown is promoted by oxytocin release, a reflex triggered by nursing; therefore neonates must spend adequate time suckling. Disruption of the pituitary-ovarian-mammary gland axis can cause idiopathic agalactia. Agalactia can be associated with premature delivery of neonates, and is suspected (by breeders) to be a potential complication of ovariohysterectomy performed at the time of a cesarean section. Because estrogen promotes lactogenesis, the adequacy of mammary development should be assessed before removal of the ovaries during cesarean section. Bitches with adequate lactogenesis at term should not be impacted negatively by ovariohysterectomy. A genetic component may be present with ' this disorder.1

Therapeutics

Lactation can be promoted if treated promptly when adequate mammary development has occurred. The administration of minidose oxytocin, 0.5 to 2.0 U per dose, subcutaneously every 2 hours should be initiated. The nurslings should be removed from the dam before each injection, and should be replaced 30 minutes later. The neonates should be supplemented adequately to ensure survival, but not excessively, so that they suckle vigorously. Gentle hand stripping of the mammary glands should take place if suckling is not vigorous, Concurrent administration of metoclopramide subcutaneously, 0.1 to 0.2 mg/ kg, every 6 to 8 hours may promote prolactin release. The administration of acepromazine at mild tranquilization dosages also may facilitate milk letdown. Therapy should continue until lactation is adequate (usually 12-24 hours later).

SUMMARY

'1'1)(' pl',Il 'li('I' of :iIlII III I1 l1il1l nl Ih('r iogC' nology i rewarding, but frusII',di ll ll! " I: I \'II II1 '\'I'ltl ll )" 11 'I'ltll ll lo)"il ' ,l( l v, II1('(':{ M i ompa rcd wi.th other 111 11 11' 11 '11 1'1 '1'"11 111111"" ,'111 111 l d l ll \ 11'1 ,,1 11/\ I() jll 'ill 'li" I' ),,()o(\ qlla lil m d i-1'1111 ' " ',," 1\ Ilil 'll l l\ 11111, ,,1 ' 1'"\\'\1 11\ 111 11 1'1'111 I 11111'/-1 IIt,II ,I i'( ' \l ol' 11 11'111 Iii '" Itt 1111 '1 '1 11 '11111 I Illli l ,III ' Illd Ii' II II ,ddl ' III I'l ' I' ll! ' dd. , 1111I"'ll I,d

420 DAVIDSON

collaboration among theriogenologists specializing in small animal practice is evidenced by growing attendance at national and international scientific meetings, increased scientific publications, and internet communications.

References

1. Davidson AP, Stabenfeldt GH: Reproduction and lactation. In Cunningham JG (ed): Textbook of Veterinary Physiology, ed 2. Philadelphia, WB Saunders, 1997, pp 482--498

2. Feldman EC, Nelson RW: Canine and Feline Endocrinology and Reproduction, ed 2. Philadelphia, WB Saunders, 1996

3. Freshman JL, Amann RA, Soderberg SF: Clinical evaluation of infertility in dogs. Compend Contin Educ Pract Vet 10:443, 1988 \

4. Goldenberg RL, Rouse DJ: Prevention of premature birth. N Engl J Med 339:313, 1998 5. Johnson C, Bari ON, Nachreiner R, et al: Effect of l3lI-induced hypothyroidism on

indices of reproductive function in adult male dogs. J Vet Intern Med 13:104, 1999 6. Kyles AE, Vaden S, Hardie EM, et al: Vestibulovaginal stenosis in dogs: Eighteen cases

(1987-1995). JAVMA 209:1889, 1996 7. Larsen R: Testicular degeneration and hypoplasia. In Tilley LP, Smith FW (eds): The 5-

Minute Veterinary Consult Canine and Feline. Baltimore, Williams & Wilkins, 1997, p 1094

8. Mostoskey UV, Padgett GA, Stinson AW, et al: Canine molecular genetic diseases. Compend Contin Educ Pract Vet 22:480, 2000

9. Olson PN, Schultheiss P, Seim HB: Clinical and laboratory findings associated with actual or suspected azoospermia in dogs: Eighteen cases (1979-1990). JAVMA 201:478, 1992

10. Root MV, Johnston SD, Johnston GR: Vaginal septa in dogs: Fifteen cases (1983-1992). J Small Anim Pract 206:56, 1995

11. Scott DW, Miller WH, Griffin CE (eds): Environmental skin diseases. In Muller and Kirk's Small Animal Dermatology, ed 5. Philadelphia, WB Saunders, 1995, p 887

12. Sobel JD: Vaginitis. N Engl J Med 337:1896, 1997 13. Thacher C, Bradley RL: Vulvar and vaginal tumors in the dog: A retrospective study.

JAVMA 183:690, 1983


Autumn P. Davidson, DVM Small Animal Clinic

Veterinary Medical Teaching Hospita I 1 Shields Avenue

University of California, Dav is Davis, CA 95616


CANINE MOLECULAR GENETIC TESTING

Danika L. Metallinos, DVM, PhD

Recent advances in molecular genetics provide the groundwork for the development of genetic tests for the diagnosis and prevention of inherited diseases. The basis for the testing and the types of tests offered are explained in this article. Veterinarians should be prepared to understand genetic testing and counseling because they are becoming important to the practice of veterinary medicine.

INHERITED DISEASES IN DOGS

Inherited diseases are common among domesticated dogs because of the population structure of dog breeds. There have been over 370 inherited diseases described in dogs, with additional diseases recognized each year. Because of the high level of inbreeding within dog breeds, autosomal recessive disorders are more common, with approximately 70% of the canine disorders inherited as autosomal recessive traits.l The establishment of a breed begins when dogs with similar physical and behavioral characteristics are bred to each other to create more dogs with those characteristics. Once the breed has been established, there are a limited number of individuals available for breeding purposes; thus, related dogs are bred together, which leads to decreased heterogeneity (genetic differences). Using this breeding practice, traits with value to the breeder can be fixed in the progeny, leading to a consistent type of dog. Unfortunately this practice, called linebreeding, also uncovers reces-

ti on, chool of Veterinary Medicine,

VIl' I'!l. I ' IN I II ~ Jl I I ( 1I ' llil li lll tvlll ~ ll l\ '.1\ 1 II AN l tvl i\ I , I 'I 'i\ t ' I'\l ' I\

Vii i 1/ 11 11 I I 1I 1 1~ 1 1 1 11 1 i ' ~ 1 11 11 '1111/ 1" 1

422 METALLINOS

sive alleles, which explains why most genetic diseases are recessively inherited.

The popular sire effect further reduces variability in dog breeds. There are a limited number of breeding animals within a purebred dog breed, and many are closely related because of the overuse of popular sires. Many breeders choose to breed to the top winning male dog, and there are no prescribed limits on the number of progeny that a male\ (or female) dog may produce. A stud dog could easily sire over 1000 puppies in 1 year. In a breed where only 5000 puppies are registered each year, this is a significant number. Advances in canine reproduction have led to the use of fresh-chilled and frozen semen, which adds to the breeding potential of sires. The overuse of popular sires leads to a limited gene pool within a population that is already limited, which can be deleterious for the breed if a sire carries the allele for a recessive disease.

Historical bottlenecks have occurred in some breeds and have had detrimental effects on diversity within those breeds. These bottlenecks occur during times of war and when people's priorities change. The Chinese Shar Pei and Portuguese Water Dog are examples of breeds that were near extinction in their respective countries before their introduction into the United States, where fanciers have increased their numbers significantly in the past 20 years.

Evidence for the decreased variability or genetic differences in dog breeds can be found by molecular analysis. To date, all dogs affected with a particular disease within a breed have the same mutation. This is not true in human populations, except in the case of populations where there is significant inbreeding. An advantage exists to reduced heterogeneity in dog breeds. It is much easier to perform a genetic analysis of inherited diseases in dog breeds than in human populations. The possibility exists to correct these problems through selective breed- ' ing once mutation tests are available.

HOW DOES OUR UNDERSTANDING OF INHERITED DISEASE AFFECT VETERINARY MEDICINE?

The advances being made in canine genetics have a profound impact on veterinary medicine, Many of the diseases seen in veterina ry medicine have a heritable basis. Breeders and clients are demanding information about genetic diseases, and the opportunity exists for v t 1"inarians to have a positive impact on the incidence of inh rited d it; '[IS 'H.

A poll taken of the 27 veterinary schools in the United tnt s showvd that only 11 offer formal genetics courses in I·h ir I I'of ss ionnl (' lIl'l'i (' 1I lum. To meet the demands of clients, v tcrin ;;l l'i llll ,' hove In II Ht ' 1'(II)lillil ing education or be If-taught g n'ti isl:4.

There is fundin g nvnilnblv for I'l'HI'III 't' h (Ill IltllI 'I' II 'd diHI'illl" /i II d(l)', I, Tn th ('(1 1'1 19 l)()H, dl))" 1'1'1'1 ,.1"1'/1 11 ,111111111'1 ,111 111'1· II Y 1111 ' 11t)1;1I1"1 l' I'jlll for jll'I)(ItIt 'ill )', dU)',1 IV 111 IltllI 'I 'II I'" 1IIIIId"1I 1I '1'111' 1' '' 1111 1) /11' III 11\1' II '

CANINE MOLECULAR GENETIC TESTING 423

attacks has been for the American Kennel Club (AKC) to develop a Canine Health FOlmdation, whose mission is to improve the health and well-being of purebred dogs. In addition, individual breed clubs have developed foundations for the improvement of the health of their particular breed. Breeders have been forced to become more open about health problems, and consumers are becoming more educated about health issues as well.

There are now over 20 genetic tests available for inherited diseases in dogs (Table 1). These tests can be used for diagnostics in the case of diseases where traditional diagnosis is invasive, and they can be used to determine breeding strategies to eliminate the diseases in future generations. DNA testing affects veterinarians working in the area of reproduction, because DNA profiling for individual identification is required for stud dogs when they are collected for either fresh-chilled or frozen semen or if they are used for breeding frequently. The AKC may also allow the use of DNA testing to register dogs from the same litter with different sires and to determine the sire in unsupervised breedings.

MOLECULAR GENETIC TESTS

Samples Needed for Genetic Testing

DNA can be isolated from any cell in the body, except red blood cells. Most genetic testing can be run using DNA isolated from buccal mucosal swabs of the dog's mouth. This is a noninvasive procedure and can be done by the owner. Buccal swabs can be taken at any age; however, puppies should be weaned to avoid the mother's white blood cells from milk giving false data. The buccal swabs, which are 6-in sterile cytology brushes, can be obtained from companies that perform DNA testing. The swab is gently rubbed with a back and forth motion on the buccal surface of the mouth and is then placed in a sealed envelope before being mailed to the company (Fig. 1). Veterinarians can keep these swabs on hand in the clinic to facilitate testing. Swabs are available free of charge by companies performing the tests. Some genetic testing companies require whole blood, which is collected into EDTA tubes and hould be refrigerated. Others accept anticoagulant acid citrate dextrose

(A D) tubes, which do not require refrigeration. Samples can also be ob ta in d fronl any ti u , in luding postmortem samples. Ideally, tissue i:4 Hil il p- froz 'n in Ii 1(lid nilrog n, but DN A can be extracted from sampk'. (r() V-VII ill II 1'1')" liI ,lI' (1'\ '("l.vr for n short p riod of time. It is difficult In ohLlill 11\11 /', 1,11'('1'1 1)1 I )NA illll)< '1 1'1 '1)111 (Ill'nlalin-(' Inb 'dd d tissues; h(lW<'VI'I', /l illi\! ' I'II IIIJ ' 11111 '/1 II) IIY '" '1'('111 1111 '/11 ' 1 )1111'1 1'/1 ill Ill<' (111111'('. Un-1111 ' 11111/1 / III 1111 ' II ' I I II I I,d I,v VI'I" I 11 111 /111 11 , II II' ,'(. Iili l III I lNA II's lH III 'V I'I <'it llll /',I' 11 \'1'1 1111 11' \ d'l l', II I II \ 11/1".1 111 III' II'I ill '" 11111'., 1111 ' I Ii /I' ll It' 1111\ 1\ "1 1' 1 II II, \ 1',' " ,'11 11,. 11 1t " 1'1 II' Iii I I I' )',

424 METALLINOS

\ Table 1. MUTATION TESTS FOR INHERITED DISEASES IN DOGS

Disease Breed

Canine leukocyte Irish Setter adhesion deficiency

Congenital Briard stationary night blindness

Cystinuria Newfoundland

Fucosidosis English Springer Spaniel

Mucopolysaccharidosis

Myotonia congenita

Phosphofructokinase deficiency

ProgreSSive retinal atrophy

Progressive retinal atrophy

Progressive retinal atrophy

Pyruvate kinase deficiency

Pyruvate kinase deficiency

Severe combined immune deficiency

Von Willebrand's disease

Von Willebrand's disease

German Shepherd

Miniature Schnauzer

American Cocker Spaniel, English Springer Spaniel

Irish Setter

Irish Setter, Cardigan Welsh Corgi

Cardigan Welsh Corgi

Basenji, Dachshund, West Highland White Terrier

Basenji

Basset Hound, West Highland White Terrier

Doberman Pinscher, Manchester Terrier Poodle, Shetland Sheepdog

Doberman Pinscher, Manchester Terrier, Pembroke Welsh Corgi, Poodle, Scottish Terrier, Shetland Sheepdog

Test Laboratory

Optigen LLC (Ithaca, NY) (607) 257-0301

Optigen LLC

GeneSearch LLC (Rockville, MD)

(301) 770-6970 PennGen Laboratories

(Philadelphia, PA) (215) 898-3375 PennGen Laboratories

PennGen Laboratories


" PennGen Laboratories

VetGen LLC (Ann Arbor, MI)

(800) 4 VETGEN GeneSearch LLC Optigen LLC

VetGen LLC GeneSearch LLC

Michigan State University


VetGen LLC

GeneSearch LLC PennGen Laboratories

GeneSearch LLC

VetGen LLC

Individual Identification nnd Pnrontn 10 All 'IV I

Type of Test

Mutation

Mutation

Mutation

Mutation

Mutation

Mutation

Mutation

Mutation

Mutation

Mutation Mutation

Mutation Mutation

Mutation

Mutation

Mutation

Mutation Mutation

Mutation

Mut, l;lll1

I )N A 111 1,1 III)', III ti l')', I I 11 'II·d 1111 111 1 , Itl i litl iI"ltl l ll , 01 1 1111 ,11111 1I, III 'I il ll)',I' "IIIII I ,til ,11 1111 11 ') ',1111 111 1111 1 1' 1111 '11" 1111' \ 1 I 111 111 11 1,11 1"


Figure 1. Samples can easily be obtained for DNA extraction using a sterile cytology brush and gently brushing with a back and forth motion on the buccal surface of the dog's mouth,

individual identification for stud dogs used for artificial insemination when the bitch and dog are not in physical proximity. In the future, DNA identification may be required for registration purposes. Presently, it is a means to permanently identify a dog. Because DNA can be recovered from hair or saliva, techniques can be used to identify animals for forensic purposes. For example, dog hair left at the scene of a crime or saliva in a bite wound might be used in criminal investigations. This is done by employing a panel of microsatellite markers to detect differences between individuals.

Microsatellites are simple sequence repeats of DNA that exist all over the genome of mammals (Fig. 2). Generally, they are dinucleotide repeats, but they can also be trinucleotide repeats or tetranucleotide repeats . During replication of the DNA, mistakes can be made, which results in the addition or deletion of base pairs within the repeated sequence, leading to size differences between individuals. Polymerase chain reaction (peR) analysis can be used to amplify the repeat from gcnomi DNA, and the product is then sized on a gel. Individuals differ in th' s'iz of the bands amplified. In Figure 3, an example of a ll1i ros, t(' lli tc rnDrl er showing individual variation in the size of the

'1'( ;'1'( ; /1'1' ( II : /1' 1'/1'1'( " I' ( ;( '/I( 11\11'1"1'( '( : ( 'I '( "1"1"1'( : '1'/1 r 'r 'r '( '/\(; ( "1' (" I' eTC/I'T' 7\ TC CA '1'( :'1'1\( '1\1 ' f\/ '1\ ( '1\1 '1\( 'N ' 1\( ' 1\( '1\ ( 'I\ ( ' f\{ ' f\{ ' 1\( '1\ ( '1\ '1'( :( '/1'1'('( ' /1' 1'( ;' 1'( ;' 1"1' ( ' /\' 1'/1 '1 '

1'( '/I I '/\/\ '1'( "1'1'( .r ;'1" 1'1 ' /1 '1'/1 ( ' /1/1/1/11 "1"1"1'( :( ;1111 '1'/1'1'1"1'/11 '1'('( '/II ' /I '1'1' /1'1'1 '/II ;1\1'

1 I IIU n • 1111 I III" I i11 /\ III jill 1111 ' 11\ II 11 111111 11 1IIIIlti (1(1i I" 11 11 111 1111" 111111 1 111111 A 1"111 II I I 111 1111111 1111 1 IIIIIIIIII I( Itl (11111 111 1 Vi llI! iii hili Jilt l lilllill I 1IIIIIvldii II

426 METALLINOS

1 2 3 4 5 6 7 8 9 IO 11 12 l3 14

Figure 3. PCR primers were used to amplify a microsatellite repeat from different dogs numbered 1- 13 and a water control numbered 14. The PCR products were electrophoresed on an 8% polyacrylamide gel and then stained with ethidium bromide prior to being photographed under UV light. PCR = polymerase chain reaction .

PCR products amplified is shown. Markers that show many differences between individuals are used for individual identification and parentage verification. Because there are so many different dog breeds with different sets of alleles, it is necessary that the microsatellites used for this type of analysis be evaluated in the breed before the analysis is used for identification purposes. The DNA sample and the set of alleles identified by this method provide permanent identification of the dog. Disputes about parentage can be determined using these methods. An example of three microsatellite markers that are part of a parentage verification panel used at the Veterinary Genetics Laboratory (University of California, Davis) is shown in Figure 4. The size of the band is written in base pairs under the marker. The alleles of the putative sires, dam, and offspring are shown to the left. Exclusion of sire 40 is demonstrated by asterisks next to the alleles that show the exclusion; however, sire 37 could not be excluded using these three markers.

Mutation Tests

Inherited diseases are caused by mutations or changes in the DNA ' of the affected individuaL DNA is the genetic material of the cell. It is composed of four bases: adenine, thymine, guanine, and cytosine. The DNA is double-stranded: adenine pairs with thymine, and guanine pairs with cytosine. The base pairs are translated into proteins using a three-base pair code for an amino acid. The dog's body is made up of thousands of different proteins. Each tissue expresses different sets of the proteins encoded by the DNA. Mutations can cause disease by

AHT121 VIASD10 CXX161 Dam 104/110 114/1 22 112 Offspring 9 6/110 106/114 1 06 /11 2 Sire 40 98*/10 4 11 0* 1 06 Sire 37 9 6/ 112 10 / 1 . 0 10

Figure 4. The microsatellite mark r re II tod nl)1'O 1I11 1 111 p. 1111 dOli. 11 11 11 Illd 011 ill ii left. Alleles are shown a Iz 0 iii 11(1( 0 pnln . 11111111111111111 IIIIW wli lllil 1111 1111 ' WillI! II 1111 to exclude Sire /.1.0 fTOm "" Ili 1111 11 11 11 01 11 11 1 11 11 1 JlIIII 1111 11 111 "," I) 11 11 :1 11" :1/1 1111 11111 Ittl exolu I (J II 111[111111 111 :1 111 11 11 1111 (L I'IIIII Y III Mrt ll 111 I tllI l" 11111 , 1'111). I ) lviI, 1.1\)


altering a protein's function or expression in the appropriate tissue. These mutations can be single-base pair changes, insertions of DNA, deletions of DNA, or rearrangements of DNA. The goal behind the molecular genetic analysis of inherited diseases in dogs is to define the mutation that causes a particular disease and to design a test specific for that mutation.

Some diseases are caused by changes in an enzyme involved in a biochemical pathway. These types of mutations can be defined by first understanding the biochemistry of the defect and then looking for a mutation in the gene that codes for the particular enzyme. Based on the type of disease, tissues involved, and other clinical data, it is sometimes possible to hypothesize which gene might be responsible for a particular disease. Because there is so much information available in mouse and human genetics, the disease gene in dogs can sometimes be a candidate from human beings or mice. The approach is to clone and sequence the gene from dogs and look for mutations in normal and affected individuals. The actual mutation can be located in the region of the gene that codes for protein, or it can be located at a site distant from the gene. It is almost impossible to prove that a gene is not responsible for a disease without using genetic analysis, because the causative mutation can be far removed from the coding region.

The type of test designed is based on the actual mutation. Some mutations change a restriction enzyme site, allowing distinction of the mutant form from the normal form by digestion of the PCR product with enzyme. Other mutations change the length of a PCR product, for example, severe combined immunodeficiency in Arabian horses, which is caused by a four- base pair deletion.4 Still other mutations are singlebase pair changes that do not change a restriction enzyme site, for example, myotonia congenita, which is a single-base pair change in Miniature Schnauzers, or Von Willebrand's disease in Scottish Terriers, which is a single- base pair deletion.2•3 More advanced PCR techniques are necessary to distinguish the mutant allele in these cases. Table 1 lists the mutation tests available in dogs. Mutation tests are breed-specific; thus, a test designed for one breed cannot be used in other breeds.

Linked Marker Tests

Determining the actual mutation responsible for a disease can be d i fficul t if th r are no obvious candidate genes. An alternative approach to id c·ntify ing th mu ta tion is to find the location on the chromosome of Illl' gVIlt' in volv('d using linl t g analysis. Linkage analysis is the d(,[ (, t'IIlillnli(l11 of' 1111 ' 1'('! .l li vl' loc,)li oll or 111 :1 r1 ' rs or ph notypes (traits 0 1' tl i f! I 'II!H'II) 11 II , I l 'hl'IIIIH HIII III\' , ' 1'111 ' I II1I'(l I'III1l'I' (If I'his for v tc rina ri ans IlI lit lil lltl ll )t· ('11 11'1 " 1111 , \ 1,(·1" 11 111' 1I11i' l ld 111 111 '1 1' 1' 11'11 111 ~ (l lh i1 1 hf'( I( ld( 'I'H huv \' 111 /1 11 ·11 .1 11 )', III Il r 1' 111 1 1, /"1 II, ' 1' 111 I '" H" ", Ili l,· II,, · l il i li ll l lll il 11/ (1111 )('1 11 )"

Id l ' lil II l1d 'III" " III ti l , 1111 ,'1 11 ,1111 III! ' 111111 111111 11 III 1 1 111 1'"11 111 ' 11 1, 'y II I VI '

428 METALLINOS

some intrinsic error rate that must be taken into account when interpreting them. Table 2 lists the linked marker tests currently available.

Dogs have 38 pairs of autosomes and the sex chromosomes (X and Y). During meiosis, four gametes (haploid genome) are formed from a diploid cell. The haploid cell contains one of each of the chromosomes. Two events occur during meiosis that are integral to an understanding of linked markers. The first is segregation, and the second is crossing over or recombination. The chromosomes are replicated during the initial phase of meiosis, with homologous pairs lining up and crossing over occurring. This means that the homologous chromosomes exchange sections of DNA with each other. During the next phase of meiosis, the homologous chromosomes are pulled apart and segregate to opposite poles of the cell. If two markers are on different chromosomes, they independently assort to the daughter cells. There is a 50% chance that they assort to the same daughter cell if two markers are on different chromosomes. If they are on the same chromosome, the chance that they assort to the same daughter cell is greater than 50%, and the markers are said to be linked. A crossover can occur between two markers, and the frequency of crossover is related to the distance between the markers. The further apart two markers are, the greater is the chance that a crossover event occurs between them. Even though the mutation causing the disease has not been identified, a linked marker may be useful in certain pedigrees to help eliminate the disease. Linkage analysis establishes the genetic distance between markers on a chromosome and between the disease gene and markers.

There are two ways that linked marker tests can be false. One way is if there is a recombination (crossover) event between the linked marker and the disease. The frequency of this happening is related to the distance between the marker and the disease gene; as a result, markers that are close to the disease gene are the most useful.

The second way that a linked marker gives false results is if a marker allele is assumed to be carried on the same chromosome as a disease allele. Although the marker is always located the same distance from the disease gene, in some individuals, different alleles of the marker can be associated with the disease allele. The results of the test are then

Table 2. MARKER TESTS FOR INHERITED DISEASES IN DOGS

Disease

Copper toxicosis

Prcd form of progressive retinal atrophy

Renal dysplasia

Breed

Bedlington Terrier

Chesapeake Bay Retri.eve l~ !\ Jl g litih Cocker Spaniel, Labrnd ur Retri eve l~ Portugll('HI' Wllh'" Dog

I ,h' lI llI " PHil, Shih ' ('y.l! , :\11 11 \ '1111 11'11 Wllt'ltl I'1! 'n'II I" ,

Test Laboratory

Type of Test

IVI",I I' I


misinterpreted. It is not possible to assume that the same disease is caused by the same gene in two different breeds. Similarly, it is not possible to assume that a linked marker test is going to be informative in a different family of dogs even within the same breed. For example, if a marker, M, is linked to a disease gene allele D* and there are two alleles at M, 121 and 124, the D* could be on the same chromosome as marker allele 121 in some families . In other families, the D* could be carried with marker allele 124, which would lead to a mistaken diagnosis of carrier status of the disease if marker allele 121 was found in an individual from the second family. Using the marker to infer the disease status could give a false-positive or false-negative result depending on the phase in that family.

COUNSELING AND THE FUTURE OF VETERINARY GENETICS

Veterinarians are often asked whether a specific disease is inherited. This is often a difficult question to answer, which can lead to frustration on the part of the breeder or client. Just because a purebred dog has a disease does not mean that the disease is inherited. Inherited diseases can also occur in crossbred dogs. There are many examples of mixedbreed dogs with hip dysplasia, hypothyroidism, atopy, and osteosarcoma. Assumptions about the mode of inheritance of a disease cannot be inferred from other breeds (because of heterogeneity between breeds) or human studies. Proof that a disease is inherited comes from either a statistical analysis of pedigrees or breeding trials. Recommendations to clients based on anything less are conjectures.

There are inherited diseases that are fixed within a breed based on breed type, which can further complicate counseling. For example, an elongated soft palate in Bulldogs is associated w ith their severe craniofacial defects. A second example is chondrodysplastic dogs, which have an increased incidence of vertebral disk disease. Dogs with large amounts of white in their coats have a higher incidence of congenital deafness than solid-colored dogs. Although not all individuals within these breeds have the medical disorders, it may prove difficult to eliminate them without changing the breed type.

In the next 10 years, more genetic tests should be available for di.agnos.ing inherited diseases in dogs, and many diseases should be b tte r und r t od and liminated . In Tables 1 and 2, there are lists of th' 1IIL1I'a li nn iJ nd lin l cd 1II.<:l rk r test available as of June 2000. Because only n ('w g\' lw lic I'I'HI:-; nr(' iJv<1 iln bl · right now, counseling for the (' lil1\iI),"il )!) (I I illl l(' ril vd d iHi'.\fIl" ill dOl' , e:1I1 ~ (' diffi lil t. Genetic counHI ' llll /', 101' do)" 111'< '1,<1 1'1'1 I III 1111II I'w ll(' I'I' 1H' lw( II' 11 11111111111 and liv s to k )',( '111 '111 ' 1·(,111 11 11' 1111 1', 1I 1\ 'I,d"I I II.l VI' I lid 1'111 1IIl II' IItil y 1'1'( ' 11 1'<1 tiog ' wilh Iill i'l ll l.d d II' I/H'I 111 11111/ 1 I III ' 11 11 ' II ' Iii " II VI ' II l iI 111 1'11 II VII 11""1' 10

1,1111 111 11111 1 1111 til 1',1 " (1111 11'11 ·111 )',1 11 \ "ii" II Ililllltl lf·. 1r IlI lt l," 11\11 11111 1'.

430 METALLINOS

of the literature, research being conducted, genetics, and important place that dogs have in our society.

SUMMARY

Inherited diseases are common among dogs. Recent advances in molecular genetics provide the groundwork for the development of genetic tests for the diagnosis and prevention of inherited diseases. As a result of this progress, genetics should become an integral part of veterinary medicine. DNA tests are safe, easy to perform, and reliable if interpreted correctly. Genetic tests only need to be performed once in a dog's lifetime, because the results of DNA testing never change. Veterinarians should be prepared to understand genetic testing and counseling because they are becoming increasingly important to veterinary medicine.

ACKNOWLEDGMENTS

The author thanks Michael Bannasch and Dr Marcia Eggleston for their assistance in preparing this article.

References

1. Patterson DF: Companion animal medicine in the age of medical genetics. J Vet Intern Med 14:1, 2000

2. Rhodes TH, Vite CH, Giger V, et al: A missense mutation in canine C1C-1 causes recessive myotonia congenita in the dog. FEBS Lett 456:54, 1999

3. Venta PJ, Li J, Yuzbasiyan-Gurkan V, et al: Mutation causing von Willebrand's disease , in Scottish Terriers. J Vet Intern Med 14:10, 2000

4. Wiler R, Leber R, Moore BB, et al: Equine severe combined immunodeficiency: A defect in V(D)J recombination and DNA-dependent protein kinase activity. Proc Natl Acad Sci VSA 92:11485, 1995

Suggested Reading Thurman TF: A Comprehensive Primer on Medical Genetics. New York, Parthenon Pub

lishing Group, 1999

Address reprints requests /:0

Danika Metallinos, DVM, PhD Department of Population Health and Reprod u bon

School of Veterinary Mcdi in One Shield Avenue

VIliy rsily o f a li fomin , I n v i ~ Do v is, ./\ t)!'i(, I ()


Glossary

Allele: Alternative form of a gene. Autosome: Those chromosomes not involved with sex differentiation. Candidate Gene: A gene implicated in pathogenesis based on protein function,

chromosomal location, or sequence homology. Chromosome: Long, single, continuous molecule of DNA. DNA is divided into

a number of chromosomes in all organisms. DNA Marker: DNA segment, often anonymous, that exhibits sufficient sequence

variation to be useful in genetic linkage analYSis and DNA diagnOSis. Founder Effect: Higher then expected allele frequency in a population as a

result of inheritance of the allele from a common ancestor. Genetic Map: Map of loci assembled by genetic linkage studies. Genome: Complete set of genes (DNA) in an organism. Haploid: Half the chromosome number of somatic cells. Linkage: The tendency for neighboring genes to segregate together during meio

sis. Locus: Unique location of a gene on a chromosome. Meiosis: The process of germ cell division that randomly allots one chromosome

from each pair to gametes and reduces the chromosome number from diploid to haploid.

Microsatellite: Repetitive DNA consisting of small numbers of repeating nucleotides.

Mutation: Spontaneous change in DNA sequence or chromosome structure. PCR: Polymerase chain reaction by which individual pieces of DNA are ampli

fied through sequential cycles of heat denaturation, annealing, and polymerization.

Phase of Linkage: Combination of alleles on parental chromosomes deduced by linkage studies.

Predisposition: Greater likelihood of disease. Restriction Enzyme: An enzyme that cleaves DNA at specific sites based on the

sequence of the DNA.

CLINICAL THERI ~ J\NOI.O(; Y

INDEX

Note: Page numbers of article titles are in boldface type,

Abortion, spontaneous, diagnosis of cause of,242-243

Agalactia, idiopathic, causes of, 419 diagnosis of, 418-419 treatment of, 419

cxz-Agonists, for periparturient premedication, 325

Amyloidosis, 398 Anesthesia, for cesarean section, 321-330

premedication for, 325 for periparturient patient requiring ur

gent nonobstetric care, 320 general, for cesarean section, 327-330 local, for cesarean section, techniques

for, 326 of neonate, 330-337 periparturient and neonatal, 315-341

cardiovascular changes during, 318-320

neurologic changes during, 316-318 respiratory changes during, 316

physiologic changes and impact on, 315-320

techniques for, for cesarean section, 323, 324

Anestrus, bitch in, prebreeding examination for, 238-241

Anovulvar cleft, closure of, 277-279 Atropine, for cesarean section, 328

in neonatal resuscitation, 355

Ba lanoposthitis, jn dogs, 253- 255 Bit h, trans ervi al insemiJla tion

I" hniq" ~H in , 291 - 304 "I l' rim' ilnd fpl 'nl l11()nitt)l'illg in, 305- 3'13

Ill o()d Hil mi ling, I" nVO nnll'H, h l',lvoiL'll1i ll (", "", :I(,d

1I" I'I'dl'l f'" 1111111 111',1' "1 " '11 111 1, 111 1" " "1'. '),11 ')d 'l 1"""" II f', II I 'III ' II

ti ll 111 11 1 1', 111 '1111 ,111 dill 1111 111,,1111 ilill I, I Ii 111111111,,11 11) III II'

Calcium requirements, during gestation, 376

for neonates, 382 of growing dogs and cats, 385-386

Carbohydrates, requirements for, during gestation, 376

Cardiovascular emergencies, in neonates, 362

Cats, familial and congenital diseases of, 396

growing, nutrition of, postweaning to adulthood, 384-390

healthy neonatal, hematologic values in, 346

young, normal biochemical values in, 348

Cervix, canine, 293-294 Cesarean section, anesthesia for, 321-330

preparation of patient for, 321-322 Chondroprotectives, for growing dogs and

cats, 388 Colostrum, nutritional value of, for

neonate, 379-380 Critical care, neonatal, 343- 367 Cystinuria, 394

Dehydration, in acutely ill neonates, 359-360

Dewclaw removal, analgesia and anesthesia for, 336-337

Diabetes insipidus, central, 401-402 nephrogenic, 394

Di abetes mellitus, juvenile, 403-404 I i, rrhea, in n ,onate, 363 I ) i ll~, , ' p , lnl , for 'sa l' an 5 ction, 327 111""1"' 11,, hl!i 'll in , t ' ,ltninnlion of, 242 111 ' 11 ''' ''''(11 ), 11111 '1111 '.1 , 1',"I\\ 'Ii<' li 'Nlinf ', (nr,

' lillJ, I"" II""" !''' I, ,, , 1)1 I I I ri"f ', I ' I 1"

111101" 1'"11 11111\ il l \1 11 rll lI lI \

11111 l it I I II 11101 I" I I I

I II

434 INDEX

Disease(s) (Continued) linked marker tests for, 427--429 molecular genetic tests in, 423--429 mutation tests for, 424, 426--427 parentage analysis for, 424--426

Dobutamine, for neonatal anesthesia, 335 Dogs, familial and congenital diseases of,

396 growing, nutrition of, postweaning to

adulthood, 384-390 healthy neonatal, hematologic values in,

345 inherited diseases in, 421--422 neonatal and pediatric, vital signs in,

344 reproduction services for. See Reproduc

tion services, canine. reproductive tract of, anatomy of, 292-

294 stud. See Stud dog. vagina and vulva of, surgery of, 271-290 young, normal biochemical values in,

347 Dopamine, for neonatal anesthesia, 335 Doxapram, in neonatal resuscitation, 355 Drugs, in neonatal therapy, complications

of,363-364 Dwarfism, pituitary, 402--403

Ejaculation failure, in dogs, 249-250 Electrolyte abnormalities, in acutely ill

neonates, 360-361 Endocrine disorders, juvenile, in puppies

and kittens, diagnosis and treatment of, 401--409

Energy requirements, of growing dogs and cats, 385

of neonates, 381 Epinephrine, for cesarean section, 326

in neonatal resuscitation, 355-357 Episioplasty, 277, 278 Episiotomy, for canine vaginal surgery,

272- 275 Erection, failure of, in dogs, 248-249

persistent, in dogs, 253 Estrous cycle(s), 222

abnormal, 220 major hormones in, 222-223

Etomidate, for cesarean section, 328 for neonatal anesthesia, 334

Fanconi's syndrome, 393-394 Fat requirements, during ges ta tion, 37(',

of growing dogs and n l ~" Wi of n · on", ',('H, :lR !

110" nl'ld ll, " IIIII'I" I,d, d,tt I iii ', n" 'I III II,tt " 1'/ (,

Feeding plan, for growing dogs and cats, 390

for neonates, 382-384 Fentanyl, for cesarean section, 328 Fetal monitoring, and uterine monitoring,

in bitch, 305-313 Fetal resorption, diagnosis of cause of,

242-243 Food(s), digestibility of, benefits of, during

gestation, 377 for growing dogs and cats, 388

Genetic testing, for inherited diseases, samples needed for, 423

molecular, canine, 421--430 Genetics, veterinary, future of, counseling

and, 429--430 Gestation, and lactation, nutritional factors

in dam during, 371- 377 Glomerulopathies, 397- 398 Glucose, in neonatal resuscitation, 357 Glucosuria, primary renal, 394

Hemorrhagic syndrome, in neonates, 362 Hyperuricuria, 394 Hypoglycemia, in acutely ill neonates, 359 Hypothermia, in acutely ill neonates, 360 Hypothyroidism, congenital, 404--408

clinicopathologic features of, 406 diagnosis of, 406--407 nervous system disorders in, 406 physical features of, 404--406 skeletal abnormalities in, 406 treatment of, 407--408

Hypovolemia, from blood' sampling in neonates, 364

in acutely ill neonates, 359- 360 HypovolemiC shock, in neonates, 362 Hysterectomy, pregnant patient

undergoing, anesthesia for, 320-321

Infertility, evaluation for, 215 of bitch, identification of, 2] 9

logical approach to, 237- 245 testing for, 231-232

Insemination techniqu s, tranB '"vi 'nl, application of, 299- 300 equipnlent fo r, 2

va luati on of, 29H , 0, in b ild" 29'1-,104 1" ' 11 '1"1' 1', of, 2')H 2\1\) " N.,w /1,.·,.1 11 1,,1 " I,,,d ll llt 'lI ld, II II'IIt" d

II I, II )' , " 111 11< 11 11' ''11(,' 1' '' 11 1,'1111,, 1 " I " I I I'l l.

results of, 301 safety concerns associated with,

300-301 uses of tech.nique and equipment for,

302-303 Interestrous interval, shortened, diagnosis

of, 415 possible causes of, 415 treatment of, 415--416

Isoerythrolysis, neonatal, 362

Ketamine, for cesarean section, 328 Kidneys, agenesis of, 394- 395

duplex and supernumerary, 397 dysplasia and aplasia of, 395- 397 ectopia and fusion of, 397 hypoplasia of, 395

Labor, premature, causes of, 416 diagnosiS of, 416 treatment of, 417

Lactation, gestation and, nutritional factors in dam during, 371- 377

Lidocaine, epidural, for cesarean section, 326, 327

Luteinizing hormone, in estrous cycle, 223

Malnutrition, in neonates, 363 maternal, reproduction and, 369- 378

Marker tests, linked, for inherited diseases, 427--429

Milk, nutritional value of, for neonate, 380 of various species, nutrient content of,

compared, 378- 379 Molecular genetic tests, in inherited

diseases, 423--429 Monitoring, of nursing puppies and

kittens, 384 of queens, during gestation, 377-378 perina tal, in bitcl1, 305-311

therapeutics during, 311-312 uterine and fetal, in bitch , 305-313

Mutation tes ts, for inherited diseases, 424, 426- 427

N l d ll ~ 1I 1" " 1,\ "I '''I lI d,, 1 "I'/ li 'lil'i ll"I " II, :l~17 N"I III Il I,d ,, 1'1 11,' " I'I It" ' , :111:1 :11.7 N" " ," ,I " I II II 'li lt 'Y, d'II I',/' III , \/, 1 111,1 NI'I"I" " 'l) "' 111 1,1, III '1 "1'1 " ,, 111 ,' ,,, ,, ' 1," ,

1' ,iI lt d .111" I I " '~" I "'11 11 1111 1' III 1111 , \ \ I I \ I 1"1 11 11 I \ 1,,1 \ I , III

INDEX

anesthesia induction in, 333-334 anesthesia of, 330-337

435

calcium and phosphorus requirements of,382

cardiovascular emergencies in, 362 cardiovascular values in, 344-346 diarrhea in, 363 drug distribution and metabolism in,

330-331 energy requirements of, 381 fat requirements of, 381 feeding plan for, 382-384 hemorrhagic syndrome in, 362 hypovolemic shock in, 362 isoerythrolysis in, 362 malnutrition in, 363 monitoring and support for, during anes

thesia, 334-336 nosocomial infections in, 364 nutrition of, 378- 384

assessment of, 378- 384 feeding plan and, 382-384

oxygen therapy in, 361-362 perioperative analgesia for, 336-337 postdelivery resuscitation in, 349- 350

cardiac compression in, 353-354 drugs in, 355-358

route of administration in, 354 equipment for, 351 stimulation of ventilation in, 352-353 warming and drying in, 350-352

preoperative preparation of, 332 protein requirements of, 381 pulmonary values in, 346--348 renal values in, 348- 349 respiratory emergencies in, 361-362 taurine requirements of, 381 thermal injury in, 364 thermoregulation in, 349 trace mineral requirements of, 382 vital signs and normal blood values in,

343-344 water requirements of, 381

Neoplasia, renal primary, 397 "New Zealand" endoscopic method, of

transcervical insemination tech.niques, 295-298

Nonobstetric care, urgent, anesthesia for periparturient patient requiring, 320

"Norwegian" method, of transcervical insemination tech.niques, 294-295

Nosocomia l infec tions, in neonates, 364 Null'''' Iti a ls, for growing dogs and cats,

, HH NI" t'i ll l' II , 11 14/1" 11/411 H' I1 I of, for I'l' I)J'olili lion,

1'/11 ,17 1, 17" , ,( 11", "," 1" ". \,/11 l/l i

,I tI '~'" I II III ti l I'llt III I 111 ·d lll l'. 1Ii ' III 11 11+1 II i ' \/1 1

I" .1 111 11 10 " , II 11 111 I tI I" \,,1, I'"

436 INDEX

u-Opioid agonists, for periparturient premedication, 325

Opioids, for cesarean section, 328-329 Os penis, fracture of, in dogs, 255 Ovulation, and fertile period, 223-224 Ovulation timing, behavior and observable

signs in, 224-225 breedings and, 229-233 concepts and controversies in, 219-235 diagnostic procedures and, 224-228 exfoliative vaginal cytology and, 225 for canine reproduction services, 212 hormonal assays and, 226-227 indications for, 219-221, 230 protocol for, 228-229 reproductive physiology and, 222-224 vaginoscopy and, 227

Oxygen, in neonatal resuscitation, 358 Oxygen therapy, in neonates, 361-362 Oxytocin, during uterine and fetal

monitoring, 311-312

Pancreatic disorders, 403-404 Paracervix, and dorsal median fold,

canine, 292-293 Paraphimosis, in dogs, 252 Parentage analysis, for inherited diseases,

424-426 Pediatric nutrition, new concepts in,

369- 392 Penis, canine, congenital abnormalities of,

250-252 disorders of, 247-258 functional abnormalities of, 248-250 neoplasms of, 256 normal anatomy and physiology of,

247-248 physical abnormalities of, 250-256 trauma to, 255-256

pH, urinary, of foods, during gestation, 377

of foods for growing dogs and cats, 386

Phimosis, in dogs, 252 Phosphorus requirements, during

gestation, 376 of growing dogs and cats, 385-386 of neonates, 382

Physical examination, prior to breeding, 237

Pituitary disorders, 401-403 Polycystic renal disease, 398 Potassium requirements, of growing dogs

and cats, 386 Prebiotics, for growing dogs and a ts, 89 Pregnancy, canine, cardi.ova, IdAI' C' hllll gU~

during, an sl'hcsi) lind , ' Iii :I () n Llrolog ir ci lllll f'PI dll1'I '1 f'" 1111, '1 111<,,, 111

111111 , :11( 1 III!

respiratory changes during, anesthesia and,316

diagnosis of, ultrasonography for, 242 hysterectomy during, anesthesia for preg

nant patient undergoing, 320-321 management of, and whelping assis

tance, 243-244 Priapism, in dogs, 253 Probiotics, for growing dogs and cats,

388-389 Proestrus, bitch in, evaluation in, 241 Progesterone, in estrous cycle, 223

measurement of, during nonpregnant diestrus, 243

Propofol, for neonatal anesthesia, 334 Protein requirements, during gestation and

lactation, 375 of growing dogs and cats, 385 of neonates, 381

Renal disease, congenital and inherited, of small animals, 393-399

Reproduction, maternal malnutrition and, 369-378

nutritional assessment and, 370-371, 372 nutritional factors for, 383

Reproduction services, canine, artificial insemination for, 213

chilled-extended semen breedings in, 213- 214

considerations for starting, 209-210 equipment needed for, 210 evaluation for infertility in, 215 insemination with frozen semen in,

214-215 mismating in, alternatives to

management of,216-217 overview of, 209-218 ovulation timing for, 212 prebreeding examination for, 211-212 pregnancy diagnosis, peripartutient

care, and cesarean section in, 215 pyometra and metritis treatment in,

215- 216 reproduction services to offer in,

210-217 semen collection and evaluation fOl~

212-213 Reproductive tract, canine, ana tomy of,

292-294 Respiratory emergencies, in n onntCH,

361- 362

f;I'1I11"I , 1I1111111" IWI , l1l l1 ll llf ',I ' I\i l 'IIII II dllf \l' 1'V Ih , " It', ') 1111

111 ' 11"" " 11 11 11,'11 " I, III IlI dll" ,I III' II I lid dUll, '( Ii ',,/I

chilled or frozen, br eding with, 220, 233 frozen, insemination with, in canine re

production services, 214-215 of stud dog, collection of, 261- 262

evaluation, 261- 262 quality of, testing of, 232

Skeletal disease, developmental, risk factors influencing, in large-breed puppies, 386, 387

Sodium bicarbonate, in neonatal resuscitation, 358

Stud dog, sub fertile, clinical management of,259-269

inability to breed but normal ejaculate in,260-261

lack of libido but normal ejaculate in, 259- 260

semen abnormalities in, 261-268 Subfertility, acquired male, causes of, 418

diagnosis of, 417-418 treatment of, 418

Tail docking, analgesia and anesthesia for, 336-337

Taurine, deficiency of, in gestating queens, 375-376

requirements for, in neonates, 381 Theriogenology, canine, frustrating case

presentations in, 411-420 clinical, 209-430

Thermal injury, in neonates, 364 Thyroid disorders, 404-408 Trace minerals, requirements of, for

neonates, 382 Tromethamine, in neonatal resuscitation,

358

Ultrasonography, for pregnancy diagnosis, 242

in ovulation timing, 228 Urethral prolapse, in dogs, 255

INDEX 437

Urethrostomy, perineal, vulvovaginectomy with, 287-289

Uterine monitoring, and fetal monitoring, in bitch, 305-313

Vagina, canine, and canine vulva, surgery of,271-290

caudal approach to, 272-275 length of, 292 surgical approaches to, 271-272 ventral approach to, 275-277

prolapse of, partial vaginectomy for, 283 Vaginal bands, correction of, 283-286 Vaginal masses, pedunculated, resection

of, 279-283 Vaginal mucosa, edematous, resection of,

279-283 Vaginal septa, correction of, 283-286 Vaginal stenoses, correction of, 283-286 Vaginal strictures, correction of, 283-286 Vaginectomy, complete, 286-287

partial, for vaginal prolapse, 283 Vaginitis, chronic, in dogs, causes of, 414

diagnosis of, 413-414 treatment of, 414

puppy, 412-413 Vulva, canine, and canine vagina, surgery

of,271- 290 Vulvoplasty, 277, 278 Vulvovaginectomy, with perineal

urethrostomy, 287-289

Water, requirements for, in neonates, 381 Whelping assistance, pregnancy

managementand, 243-244 Whelping date, prediction of, 221

Xylazine, for periparturient premedication, 325

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