Electrical and extraluminal contractile-force activity of the duodenum of the dog

Electrical and Extraluminal Contractile-Force

Activity of the Duodenum of the Dog

PAUL BASS, PH.D., AND JAMES N. WII.EY

M ANY ATTE3~IPTS have been made to elucidate the in terplay between the two outer muscle layers of the bowel. T h e studies have in-

volved a variety of methods, tissue preparat ions , and species. T h e litera- ture, even before the turn of the century, is conflict ing as to the mechanics of the muscle layers. T h e att i tudes of the early workers toward this prob- lem were described by MalP in 1896. t t e suggested that a single bowel contrac t ion consists of a contrac t ion a nd re laxa t ion of the circular coat ahe rna t ing with a cont rac t ion and re laxa t ion of the longi tud ina l (:oat. Bayliss and Starl ing in 1899, using an "en te rograph ," were a m o n g the first to record the separate activities of circular and longi tudina l muscle.'-' A h h o u g h their data showed that the activity recorded in the circular axis could be s topped wi thou t abol i t ion of longi tud ina l axis contract ions (Fig. 5"), these au thors concluded that the " two (:oats always contract at

the same time. ''2 Othe r early workers are in agreement that the two nmscle layers work together, a-a T h e bulk of the evidence, par t icular ly data ob ta ined f rom isolated guinea-pig ileum, would indicate that there is a coord ina ted reciprocal ac t iv i ty - - tha t is, one coat contracts as the o ther retaxes7 -~ Th i s coord ina ted proper ty exists in o ther tissues and other speciesJ "-'-~z Ra i fo rd and Mulinos, using unanesthet ized dogs prepared with exter ior ized segments of bowel, elegantly demons t ra t ed that the two muscles could respond differently to various stimuli. ~s-'-'° Recen t technical developments have allowed us to evaluate some of the propert ies of the two muscle layers of the duodenum. 2~' 22

T h e basic electric r h y t h m (BER) is involved in regula t ing local spike potentials and mo to r p h e n o m e n a of the d u o d e n u m . 2a I t has been repor ted that a reduced f requency of the duodena l B E R occurred caudad to a l igature site. '-'a-26 Spike potentials and local moto r contract ions, when they occurred, bore a strict 1:I re la t ionship wi th the two B E R frequen-

I:rom the Research Laboratories, Parke, Davis 8e Company, Ann Arbor, Mich. The authors thank Dr. A. C. Bratton, Jr., for his interest in this study, Mr. A. J.

Dresner for advising on the statistical analyses of the data, and Dr. D. R. Bennett for discussion and critical review of the manuscript.

© 1965 by HO~,_BEr~ MEDICAL DIVISION • HaRPZ~ & ROW, PUBLISHI~RS, New York.

New Series, Vol. 10, No. 3, 1965 ]8~

Bass & Wiley

cies. 2a It has also been demonstrated that the activities of the longitudinal and circular axes of the bowel can be differentiated by miniature extraluminal contractile force transducers. 21' 2_~ These transducers have been utilized in this study to demonstrate the relationships between the muscle layers and the electric activity above and below an anastomosis site.

M E T H O D S

SENSOR UNITS

The technics of recording bowel activity with extraluminal transducers and electrodes have been reported. 2~" 2z Several of the sensor units used in this study incorporated structural modifications. Firstly, the transducer and electrode were combined in a single uni t (Fig. 1, A and B). Sec- ondly, the shape of one of the transducers was altered (Fig. 1, C).

In the combined sensor units, the surface electrode consisted of a 3-ram. length of plat inum wire soldered to a lead wire and placed in a groove in

A B ~ j /j

Fig. 1. Diagrams of recording units: A, top, and B, bottom view of combination transducer-electrode, respectively; C, top view of transducer used in transverse axis of duodenum.

the bottom of a rectangular mold. The assembled strain gauge was then centered over the electrode and insulated from the electrode by a layer of silicone rubber (Medical Silastic 372~). The entire unit was then covered with Silastic, with the exposed electrode protruding from the

*Dow-Corning Corporation, Midland, Mich.

184 American Journal of Diqestlve Diseases

Duodenal Activity

bot tom. A similar un i t composed of the t ransducer and a needle electrode 27 was also constructed. Both surface and needle electrode units were used in this study.

T h e t ransducer used in the circular axis (Fig. 1, C) was similar to the un i t used in the longi tud ina l axis in this study. A detai led descript ion of its const ruct ion has been g iven? 2 T h e gauge clip was 4 x 9 ram. and was shaped in an l l-rnm, radius of curvature. A tempera ture-compen- sated epoxy-backed foil strain gauge ( E A - 0 9 - 0 9 0 D G - 1 2 0 ~) was b o n d e d to the convex surface of the clip. T h e conduc to r wires were soldered to the gauge terminals, led over the 9-ram. edge of the clip, and directed to the opposi te side across the concave surface of the clip. T h e gauge clip assembly and lead wires were enclosed in respective Silastic materials (Medical Silastic 372 and Medical Silastic 372 tubing; .062 in. I.D. x .125

in. O.D.). T h e transducers were 14 mm. long, 6 mm. wide, and 4 ram.

deep. Several sensor units were used in each dog. Lead wires f rom the sensors

were soldered in to a 17-contact female connector . T h e connec tor was sealed into a modif ied T h o m a s cannula wi th acrylic plastic and both connector and cannu la covered wi th a th in layer of Silastic ( R T V 382).

SURGICAL PREPARATION

Duodena l anastomoses were p repared in hea l thy female (logs. T h e m i d - d u o d e n u m was transected and anas tomosed end to end. Af ter an interval of 2 weeks, the record ing uni ts were sutured on to the serosal surface of the bowel. Details of the surgical implants have been described.21.27 In each p repara t ion the distances between the midpo r t i on of the sensor uni ts and the anastomosis were noted. These were a mean of 24 mm. above and 23 ram. below the anastomosis.

T w o different a r rangements of the sensor units were used. I n one ar rangement , each set consisted of a t ransducer 21 in the longi tud ina l axis, a t ransducer (Fig. I, C) in the transverse axis and a needle electrode -~7

between the two transducers. One set of 3 uni ts was implan ted cephalad, and one set caudad to the anastomosis. Each set was al igned in the same

transverse p lane of bowel (Fig. 2, insert). I n the o ther a r rangement , the

combined sensor units were used (Fig. 1, d and B) . T w o units were placed cephalad and two caudad to the anastomosis (Fig. 3, insert) . I n

bo th arrangements , the transducers were pe rpend icu la r to each other to

record the activity in the longi tudinal and transverse axes of the bowel.

*Micro-Measurelnents, Inc., Romulus, Mich.

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EXPERIMENTAL DESIGN

T e n dogs were prepared. Nine experiments were performed on 2 dogs with the separate sensor units and 17 experiments on 8 dogs with the combined sensor units. Several of the latter experiments served to fanlil- iarize us with the technics and to establish criteria for the quant i ta t ion of data.

Each exper iment consisted of two stages taken in sequence. In Stage 1, a control was obtained dur ing the first hour of recording. In Stage 2, morphine sulfate (100 ~g./kg.) was injected I.V. and the effects recorded for 15 min. Experiments on any single dog were separated by at least 5 days. Dogs were routinely fed at 3 P.M., and recordings were started at 8 A.M. All records were obtained f rom unanesthetized healthy dogs.

RECORDING

Electrical recordings were obtained at a tfme constant of 3 sec. Occa- sionally, to reduce drift in the BER, recordings from the combined electrode-transducer were obtained at a time constant of 0.03 sec. T h e transducer circuitry has been described, zl Physiologic and pharmacologic exper imental evidence strongly indicates that the transducer oriented in the longitudinal axis records predominant ly longitudinal-muscle activity, and the transducer in the transverse axis records predominant ly circular; muscle ac t iv i tyY' 22 T h e "life" of the chronically implanted transducers is more than 90 days. All recordings were obtained on an 8-channel pen- writer (Offner*).

RECORD ANALYSIS

Visual examinat ion of the records of the 26 experiments revealed a close similarity, including the electric patterns observed from either the needle or the surface electrodes, whether they were par t of the separate or combined sensor units. Accordingly, the records used in the analysis were obtained from 2 dogs with separate sensor units and 1 with the combined units. T w o records from each of 3 unanesthetized dogs (6 records) were selected for analysis on the basis of absence of animal movement. Animal movement causes electrical artifacts.

In each of the two stages of the selected records, all BERs, bursts of spike potentials, and contractions were counted for their rates of occur- rence. From each stage of each record, detailed measurements of the various segments of the 3 parameters (BERs, bursts of spike potentials,

~Offner Div., Beckman Instruments, Inc., Schiller Park, III.

186 American Journal of Digesflye Diseases

Duodenal Activity

and contractions) were done on 10 samples selected at predetermined intervals7 a The pooling of data for each segment ill a given stage from the 6 records numbered a total of 60 measurements. All measurements were subjected to an analysis of variance. If the F value at the I~o level was found to be significant, the treatment means were compared in a Duncan nmltiple range test 49 (F: 4.94; degrees of freedom: 3-treatment, 20-error). Individual dog data were used for correlation and regression analyses between the electric and nmscle activities on combined control and morphine data.

When the combination units were used, 2 electrical records were obtained from each area of bowel. Only 1 of the electrical records from above and below the anastomosis was used in the tabulation of data.

RESULTS

CONTROl. ACTIVITY

Figure 2 is an example of electrical and transducer activity above and below the anastomosed site of the duodenum. As shown in the figure, the h'equency of the BER is less below the anastomosis. There is a definite relationship between the spike potentials and the BER in that the spike potentials follow the peak (b) of the BER even when the BER is generated at a reduced rate. A 1:1 relationship exists between spike potentials and contractions, and is more pronounced in circular-muscle than in longitudinal-muscle activity.

The quanti tat ion of electric and contractile activity is sunnnarized in TabIes I and 2. The statistical comparisons are summarized in Fig. 3. Tile electrical activities (both BER and spike potentials) are similar to those seen in ligated-loop studies7 ~ The most prominent feature is a

decrease in frequency of the BER below the union. The BER rate is

19.0 cpm above and 14.6 cpm below the anastomosis. The other major

change in the BER below the anastomosis is an increase in duration of

its c-a' portion from 0.4:3 sec. to 1.34 sec. This segment of the BER is apparently the main portion al[ected by the anastomosis.

Another alteration seen below the anastomosis is that spike potentials occurred sooner on the BER (Table 2, b-d). Where b represents the peak of the BER and d is the initiation of the spikes, d occurs on the

average of 0.84 sec. after b, cephalad, but is present 0.38 sec. after b,

eaudad to the anastomosis. The contractile force from the same axis of the bowel does not differ

above and below the junction. In comparing the two axes at the same

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level of duodenum, the transverse axis consistently demonstrates greater force than the longitudinal axis (Table 2).

MORPHINE t~FFECT

For the first 30-60 sec. after drug administration, the frequency of the BER below the anastomosis approaches normal (Fig. 5), but this is not maintained (Fig. 4). At the low dose of morphine used, the response of the circular muscle is greater than that of the longitudinal muscle (Fig. 4 and 5).

Detailed measurements indicate that below the anastomosis, morphine significantly shortens the c-a' portion of the BER from a control level

h I

17_2f_3J

T 3 , ~ Z

lOsec T1mv

Fig. 2. Electric and motor activities cephalad and caudad to anastomosed duodenum. Insert indicates arrangement of separate electrodes and transducers, and their corresponding tracings, indicated by El, T1, and T 2 above, and E2, T3, and T~ below the anastomosis (A-B). A cycle of BER has been labeled. Point of init iation of major positive deflection is a, its maximum is b, lowest ampli tude of complex is c, and start- ing point of next cycle is a'; start and end of burst of spike potentials are d and e, respectively. Calibrations for transducers and electrodes are on right. Note closer relationships between circular mnscle activity and spike potentials than between longitudinal muscle and spiking activity.

188 American Journal of Digestive Diseases

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of 1.34--0.96 sec. ( T a b l e 1 and Fig. 3). T h e dit[ercnce be tween cephalic

and caudal segments is no longer significant (0.37 versus 0.96 see., T a b l e

1 and Fig. 3). T h e lack of significance be tween 0.37 a nd 0.96 sec. indi-

cates the var iabi l i ty of the parameter . T h i s var iabi l i ty is due to the

in i t i a l and occasional shor ten ing of the c -a ' por t ion of the B ER while

the a n i m a l is u n d e r the inf luence of morph ine . ~Ihe var iab i l i ty of the

c - a ' po r t ion does no t p roduce a signif icant over-all ettect on the f requency

of the BER (14.6 versus 15.3 c . /min . ) below the anastomosis. Both above

and below the anastomosis, the d u r a t i o n and n u m b e r of spike potent ia l s

are increased by morph ine , and there is a cor responding increase in the

n u m b e r of BERs wi th spike potent ia ls (Tab le 2 and Fig. 3).

T h e r e is a dif ferent ia l response of the two muscle layers to the m o r -

TABLE 1. BASIC ELECTRIC RItYTHM OF ANASTOMOSED DUODENUM EXPRESSED AS MEAN OF MEANS

Duration (sec.) Amplitude (my.) Frequency

Condition,s a-c* c-a' a-b b-c ca" (cpm)

Control Cephalad 2.70 0.43 0.80 1.15 0.33 19.0 Caudad 2.79 1.3~ 0.86 1.15 0.32 14.6

Morphine Cephalad 2.75 0.37 0.83 1.13 0.28 19.3 Caudad 2.81 0.96 0.86 1.14 0.26 15.3

F values N.S.~ 28.7 N.S. N.S. N.S. 59.6

*For explanation of symbols, see legend to Fig. 2. -iN.S., no statistically significant differences at the 1% level.

TABLE 2. SPIKE POTENTIALS AND MUSCULAR ACTIVITY OF ANASTOMOSED DUODENUM EXPRESSED AS MEAN OF MEANS

Condition,s

Muscle Max. activity

Duration ampti- [orce Latency (sec.) rude dis- % BER (gin.) from d to

No. discharge with contrae- b-d d-e charge (my.) spikes Circ. Long. tio~ (see.)

Con trol Cephalad 0.84 0.73 3.4 0.60 31.2 12.0 5.5 0.12 Caudad 0.38 0.69 2.6 0.30 39.4 10.2 5.7 0.20

Morphine Cephalad 0.59 1.05 6,1 1.00 83.3 24.7 4.6 0.09 Caudad 0.32 1.27 6.1 0.52 93.6 28.6 10.(~ 0.71

F values 6.7 17.9 2t.6 5.4 29.2 9.8 N.S* N.S.

*N.S., no statistically significant differences at the 1~) level.

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phine . T h e force of the l o n g i t u d i n a l muscle on e i the r side of the anasto-

mosis shows no s igni f icant increase af ter the d rug (5.5 versus 4.6; 5.7 versus 10.6, T a b l e 9). I n m a r k e d contrast , the c i rcu la r layer s ignif icant ly

( F ~ 9 . 8 ) increases the force of its con t rac t ions twofo ld above (12.0-

24.7 gin.) a n d ahnos t t h r ee fo ld be low (10.2-28.6 gin.) the j unc t i on . As n o t e d ear l ier , m o r p h i n e is ab le t e m p o r a r i l y to increase the f requency of

the BER. W h e n this occurs, the f requency of the c i rcu lar -muscle con- t rac t ions is also increased to m a i n t a i n the 1 : 1 r e l a t i o n s h i p wi th the burs ts

of sp ike po ten t i a l s and the BER. T h e a l t e r a t i ons p r o d u c e d by m o r p h i n e tha t a re s igni f icant a t the I~/~

level are c o m p a r e d a n d s u m m a r i z e d in Fig. 3.

Conditions tested I A B c I ° 1 Spikes/dlscharge; duration (d-e);

spiking discharge (sac.); °/o BER wi÷h spikes; muscular activity circular (grn.)

Frequency of BER (c./m|n.)

Max. amplitude of spiking discharge (inv.)

Duration (c-a') of BER (sec.)

Relationship o{ spiking to Br-R (b-d), sec.

B 0 A I c i

B I

I ° L B I c l A )

Fig. 3. Results of conditions tested when subjected to Duncan's multiple range test. ~'~ A indicates control, cephalad to anastomosis; B, control, caudad to anastomosis; C, response to morphine, cephalad to anastomosis; D, response to morphine, caudad to anastomosis. Any experimental conditions not underscored by the same line are significantly different at the 1% level; conditions underscored by the same line are not significantly different from each other.

190 American Journal of Diges'tlve Diseases

Duodenal Actlvi'ly

RELATIONSHIP OF N U M B E R OF SPIKE POTENTIALS, DURATION OF

SPIKING AND ACTIVITY OF CIRCULAR AND

LONGITUDINAL MUSCLE

The data were subjected to a correlation coefficient (r value) analysis in order to measure the degree of association between (t) the number of spike potentials per discharge and the longitudinal- and c'ircular- muscle activity, and (2) the durat ion of spiking and the activity o£ the two muscle layers (Table 3). Fisher's Z transformation was used to test the significance of all computed r's.

There is a significant correlation between the number of spikes per discharge and circular-muscle activity. In contrast, 4 of the 6 r values relating spike potentials to longitudinal-muscle contractions are not significant. Th e 2 that are significant were computed from data obtained

I 50g FORCE

~'7

^ ]':: :L;~I Q T.C. =03see "

I

T3~t / ',

i < , I

T 4. _./-- ./ _ .X, ...... .-, /,, / ~ , ~ / ~ . . / - ~ ~ _ / ~ . ~ /x ±

Fig. 4. Morphine effects o11 dectric and motor activities cephalad and caudad to allaStol-nosed £hlodellunl. Diagram at left indicates arrangement of combined electrode- t ransducels and their respective tracings. Cal ibra t ions are as in Fig. l, Note two f r equendes of contract ions above and below anastomosis , and differentiaI response between two muscle layers even when gains of amplif iers (as seen by cal ibrat ion bars) arc grcaler for T~ an d T~ than for T~ and T.>

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below the anastomosis and are near the lower limit for significance. The duration of the burst of spike potentials is positively correlated with circular-muscle activity in 5 of the 6 r values. Again in contrast, 4 of the 6 values relating durat ion of spiking to longitudinal-muscle activity is not significant. The random contractions in the longitudinal axis may account for the occasional positive correlation of spike-potential parameters with longitudinal-muscle force.

Graphic representations of the relationships between the electric and transducer activity above the anastomosis are shown in Fig. 6 and 7 and activity below the anastomosis is shown in Fig. 8. Regression slopes relating the number of spikes and the duration of spiking to the activity of circular muscle indicate a strong positive relationship. This relationship is absent between the two spike-potential parameters and the longitudinal muscle.

E1

c[

2V3J

T4 ~Osgc i-troY

Fig. 5. Electric and motor activities cephalad and caudad to anastomosed duodenum within first rain. of adminis ter ing morphine . Arrangement is as in Fig. 1. Note similar frequencies above and below anastomosis and differential response between two muscle laT,ers.


Duodenal Activity

TABLE 3. CORRELATION COEFFIC]IENT VALUES (r): NUMBER OF SPIKE POTENTIAI,S, DURATION OF SPIKING AND ACTIVITY (FORCE) OF

C1RCULAR AND LONGITUDINAL MUSCLE OF DUODENUM CEPHALAD AND CAUDAD TO ANASTOMOSIS

Dog No.

No, o] spikes versus iorce Du)alim7 of spiki*)g versus force

Circular Longitudinal Circular Longitudinal

Cephalad Caudad Cephalad Caudad Cephalad Caudad Cephalad Caudad

A-6 .472 ~ .956* .081 .472* .335 .883" --.150 .406 A-9 .852* .842* .384 .309 .500 e .531" .575* .289 A-10 .965 * .926 * --.102 .612" .732* .920* --.268 ,602"

*Significantly different from zero at the 5% level.

Fig. 6. Reg~'ession equations, lines, and their respecti*.e confidence limits at 0.05 level eepha- lad to anastomosis, (1) 1elating nu,nber o{ spikes and force in transverse axis (circular muscle), and (2) lack of relationship between number of spikes and force in longitudinal axis (longi- tt,dinal muscle).

50

45

40

35

3O

25

2O

I0

-5

-~0 0 z 3 4 5 6 7 8 9

NUMBER OF SPH(ES P[R DIS£NARGE

A s imi l a r r e l a t i o n s h i p exists b e t w e e n the e l ec t r i c a n d c i r c u l a r - m u s c l e

ac t i v i t y b e l o w the a n a s t o m o s i s (Fig. 8). T h e r eg re s s ion l i n e b e t w e e n elec-

t r ic a n d l o n g i t u d i n a l - m u s c l e ac t iv i ty was o m i t t e d f r o m Fig. 8. As m a y

be o b s e r v e d in the records , a n d as s h o w n in T a b l e 3, this m u s c l e l ayer

b ehaves in a f a s h i o n s i m i l a r to t i le l o n g i t u d i n a l m u s c l e a b o v e the anas to -

mosis. T h u s , b o t h a b o v e a n d b e l o w the anas tomos i s , a d i r e c t r e l a t i o n s h i p

exists b e t w e e n the force of c o n t r a c t i o n of t he c i r c u l a r m u s c l e a n d the

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45

40

35

30

25

. ~ z0 t ~ a

¢-' 15

10

5

0

-5

-1O

I I I t I ~

ov = -3.05 +(Z2.SI)x :

"' ;iiiiiiiii;iii

.40 .GO .80 1.00 t20 DURATION (d-e) OF SPIKING PlSCI4ARGE (sec)

Fig. 7. Condi t ions as in Fig. 5, wi th du ra t ion of spiking related to two axes (muscle layers) of bowel.

50 '::~ I/ii~i ii 45 :ii!!i!

35 .:[ii!:

5 . . o . .

~ / / ~ / ITRANi~RS:'A~XIS~ I ~ / / (TRANSVERSE AXIS,)|

I Z ,3 4. 5 6 7 8 B 20 .40 .60 .BO tO0 1.20 1.40 1.60 t.80 ?.OO NUMBER OF SPIKES PER DISCHARGE DURATION(d-8) OF SPIKING DISE!.IARGE (see)

Fig. 8. Regression equat ions , lines, and their respective confidence l imits at the 0.05 level caudad to anastomosis . At left, n u m b e r of spikes per discharge related wi th force in transverse axis, At r ight , du ra t ion of spiking related wi th force in transverse axis (circular musc le ) .


Duodenal AcfivH'y

number and dura t ion of spike potentials. This relat ionship is not obvious between the electric activity and the longitudinal muscle.

T h e correlation studies also indicate that the transducers used in these experiments are as sensitive as the electrodes in detecting muscle activity. A single spike occasionally would not correlate with any alteration in force; however, two spike potentials would frequently be accompanied by a rise of 5 gin. of tension (Fig. 6 and 8).

TONAL CHANGES ABOVE AND BELOW THE ANASTOMOSIS

There are differences in the amount of base-line force above and below the anastomosis. In both axes above the anastomosis, there are periodic sustained increases in force (tonus) with contractions superimposed on them. These tonal changes are not evident below ttle anastomosis. Th is contrast may best be seen by placing a straighbedge at the base of tracing T~ and T:~ in Fig. 2. Th is difference is also present in Fig. 4 and 5. Dur- ing the control period, when tonal changes are readily recorded, there is no apparent electrical counterpar t as recorded with the extracellular electrodes. T h e differential tonal change was also evident following the administrat ion of morphine. T h e drug init iated one or two spasms equal to 36 gm. of force in the circular muscle above the anastomosis, but less than 4 gin. of tonal change occurred in the circular muscle below the anastomosis.

DISCUSSION

T h e BER is involved in regulating local motor phenomena. In this anastomosis study the BER caudad to the section possessed a significantly lower frequency rate, similar to what was seen in the ligated bowel. -°a These two BER rates bear the same relationships to the spike potentials and the circular muscle contractions. Hence, the present technics can be taken as fur ther evidence that the BER governs the init iat ion of each burst of spike potentials. Since the spike potentials are directly related to the magni tude of the circular-muscle contraction, the BER also governs when the circular muscle contracts. Thus the picture emerges that the BER has its genesis in the longitudinal muscle, 2s' ~.~ and the spike potentials are related to circular-muscle contractions. T h e BER in the longitudinal muscle can set the stage for the discharge of spike potentials, probably from circular muscle. T h e number and durat ion of spike potentials are related to the magni tude of the circular-muscle contraction. I t has not been clarified which factors determine whether the BER will be accompanied by a burst of spike potentials.

T h e analysis of the data indicated a relat ionship between the spike

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potentials and circulm-nmscle contractions. In contrast, no relationship was found between spike potentials and longitudinal-muscle activity. Several possible reasons exist for the inability to demonstrate a relationship. Our method of recording with extracetlular electrodes does not differentiate the origin of the potential. This method of recording can give similar patterns whether the electrode is in serosa, mucosa, or muscle.29, a0 Th e layer of longitudinal muscle may not generate a large enough spike potential to be detected by extracellular electrodes. Pos- sibly the potentials from the longitudinal-muscle layer are masked by tile spike potentials from the circular muscle or even by the BER itself. For whatever reason, our results indicate that no detectable spike potentials are related to recorded longitudinal-muscle contractions.

Motor 24 or BER "-'> '_,6 frequencies in the small intestine are decreased below" a point of anastomosis or clamping. T h e study on the ligated bowel confirms that the two parameters are decreased by the same amountY 3 Our present study extends the earlier observations by demon- strating that both muscle layers decrease in their contraction rates below the area of insult. This decrease in activity below the section is not due to any permanent damage in the bowel because morphine was able temporarily to increase the frequencies to normal rates.

T h e mechanism by which morphine depressed longitudinal-muscle activity has undergone intensive study. Trendelenburg devised a technic with the ~ inea -p ig ileum which demonstrated that morphine prevents contraction of the longitudinal muscle-- the preparatory state required for isolated ileum to initiate a local reflex. 7 This along with other in vitro methods demonstrates that morphine can partially antagonize bowel contractions induced by 5-hydroxytryptamine (5-HT) a>4° and hista- minea2, aa, as, 40 and reduce the release of acetycholine from isolated ileum, aa,~14a Gaddum and Picarelli have postulated the presence of two types of 5-HT receptors in the small bowel, a5 One of these (M receptors), believed to be in nervous tissue, is blocked by morphine. Day and Vane have presented evidence indicating that morphine antagonism of 5 -HT induced contractions is mainly due to receptors sensitive to morphine which are located on the intrinsic nervous tissue, a9 Th e site of action of morphine has also been associated with the postganglionic sympathetic system of the ileum. 4~-4(; T h e drug can antagonize the action of dopamine and sympathetic-nerve stimulation in the isolated guinea-pig .iejunum.4~ Th e peripheral action of morphine has been associated with cholinergic, adrenergic, and serotonergic systems. Presently, we cannot say which system or mechanism is the most important for separating the activity of

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longitudinal f rom circular muscle. In contrast to its effects on motor activity, these and previous observations indicate that morphine does not markedly alter the BER. 2:~, 47 Therefore, the above three systems are not involved in the characteristics of the BER. This is fur ther evidence that the BER is myogenic rather than neurogenic in origin.

T h e ability of morphine to affect differentially the two muscle layers of the colon in vivo was demonstrated in 1934 by Raiford and Mulinos. 2° We have confirmed this property of the drug in the intact duodenum of unanesthetized dogs. This type of differential response and other observations lead to the following: (1) T h e number and durat ion of spike potentials are directly related to the force of circular muscle contractions. (2) T h e number and durat ion of spike potentials are also directly related to increases of in t ra luminal pressure. 23 (3) I t follows that increases of intraluminal pressures are due to the activity of circular muscle.

T h e term toners is difficult to define. I t seems acceptable to consider it as a shift in base-line tension, with superimposed phasic contractions. 4s On the basis of this definition, the loss of tonus below the anastomosis site suggests that this type o[ smooth-nmscle activity is also controlled from the upper port ion of small intestine. T h e inability of morphine to stimulate tonal changes below the anastomosis in our study and in other investigations 44 indicates that tonus in the duodenum is a very sensitive parameter and may easily be lost by the slightest manipulat ion. T h e loss of tonus, the lack of response to morphine, and the inability to record electric activity associated with tonal changes suggest that this type of activity has a genesis different from the rhythmic contractions of either circular or longitudinal muscle.

SUMMARY

Electrodes along with extraluminal contractile-force transducers have been utilized to study the relationship between the electric activity and the circular- and longimdinaI-muscte layers just above and below an anastomosis site in the duodenum of unanesthetized dogs prepared for testing over a period of time. The transducers differentiated the muscle activity of the two axes of the bowel.

T h e basic electric rhythm (BER) of the duodenum cephalad and candad to the anastomosis was I9 and 14.6 cpm, respectively. This decrease in frequency was accompanied by an increase in the c - a ' port ion of the BER. T h e init iat ion of the burst of spike potentials (d) was closer to the peak of the BER (b) below the anastomosis.

Morphine was used to enhance the num b er of spike potentials per

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burst and circular-muscle activity. There was a differential response by the two muscle layers to the drug, in which the activity of the circular muscle became continuously rhythmic and of high amplitude without affecting longitudinal-muscle movements. Each of the two BER frequencies still governed the initiation of each burst of spike potentials and the corresponding circular-muscle contraction.

The maintenance of the relationship among the BER, spike potentials, and circular-muscle activity leads to the following concept: The BER, generated from the longitudinal muscle, governs the conditions which determine when the circular muscle will generate spike potentials. The number of spike potentials and duration of spike potential bursts determine the magnitude of the circular-muscle contraction.

The anastomosis also initiated a differential effect in the tonus above and below the section. Tonal changes were minimal or absent below the transected portion of bowel. The method was not capable of detecting the electric activity related to tonal alterations.

Department of Pharmacology Parke, Davis 6 ~ Company

2800 Plymouth Rd. Ann Arbor', Mich.

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Electrical and extraluminal contractile-force activity of the duodenum of the dog