Functional Development Coronary Collateral Circulation

Functional Development of the Coronary CollateralCirculation During Coronary Artery Occlusionin the Conscious Dog

Colin M. Bloor, MD and Francis C. White, BS

We studied changes in the coronary collateral circulation during coronary arteryocclusion in 14 conscious dogs by: a) determining simultaneous changes inperipheral coronary pressure (PCP) and retrograde flow (RF) after abrupt cor-onary artery occlusion; b) correlating these functional indices with quantitativeanatomic indices (AI) of coronary collateral development (Menick et al: Am HeartJ 82:503-510, 1971); and c) observing changes in these indices after repeatedreocclusions of a coronary artery. These dogs were subjected to left circumflexcoronary artery (LCCA) occlusions for 2 hours to 8 days; pressure tubes wereimplanted in the aorta and LCCA, the latter tube placed distal to an occlusive cufffor PCP and RF measurements. Afterwards the animals were sacrificed, their heartsinjected with a modified Schlesinger's gelatin mass, and Al determined. During 2to 24 hour LCCA occlusions (11 dogs) mean PCP rose to levels 50 to 80% of pre-vailing aortic pressure. During repreated 2- to 24-hour occlusions (2 dogs) in thesame dog, the rate at which PCP rose increased. Retrograde flow was unchangedduring 2- to 24-hour occlusions. Anatomic indices of these dogs were in the samerange as those observed in unoccluded controls. NThen LCCA occlusion was main-tained for more than 4 days (3 dogs), mean PCP rose during the first 24 hoursand then remained stable; RF did not change until 4 days into occlusion and thenincreased. Anatomic indices of dogs occluded for more than 4 days were signifi-cantly greater (P < 0.001) than those of the 2- to 24-hour occlusion groups. Ourstudv shows that: a) the early PCP rise after occlusion is not associated with anincrease in RF, b) RF is a better index of collateral function and c) RF correlatedwell with the anatomic development of the collateral bed (Am J Pathol 67:483-500, 1972).

IN PREvious sTUDIEs in the anesthetized dog, using pe-ripheral coronarv pressure, retrograde flow and isotope clearances as in-dices of coronarv collateral blood floW,'- no evidence was found forincreased frinction of the coronarv collateral circulation during the firstfew davs after the onset of acute coronary arterv occlusion. Thesesttudies wvere in agreement with earlier morphologic studies,8 whichshow-ed no increase in the size or number of intercoronarn collaterals

From the Department of Pathology, Universitv of California, San Diego, Schoolof NMedicine, La Jolla, California.

Supported by MIIRU Contract PH-43-68-1332, Grant HE-12373 US Public HealthService Program Project Grant HE-12373 and the San Diego County Heart Association.

Accepted for publication Dec 13, 19 1.Acddress reprint requests to Dr. Colin MI. Bloor, Department of Pathology. University

of California at San Diego, School of Medicine. La Jolla, Calif 92037.

483

484 BLOOR AND WHITE American Journalof Pathology

until at least 4 to 5 days after the onset of coronary artery occluision.How-ever, recent studies of the coronary collateral circulation in theconscious dog suggest that a marked increase in coronary collateralcirculation can occur w-ithin a few- days after coronary artery occlu-sion." These latter studies used indirect indices of collateral flow-iv ,peripheral coronar- pressure and augmented coronary blood flowthrough the unoccluded coronary arterv, wvhich may account for theirvariance wvith earlier investigators. In acute experiments involvingligation of the anterior descending branch in dogs, Rees and Redding5followed xenon clearances for 10 days in the closed-chest state andobserved a lag of 3 to 4 days after infarction before the clearancesstarted to rise, a finding consistent wvith previous morphologic stud-ies.'-' A recent study in our laboratory showed the feasibilitv ofmeasuring and correlating retrograde flow- in the conscious dog with aquantitative anatomic index of coronary collateral circulator- devel-opment.11 Thus, our study intends to: a) determine simultaneouschanges in peripheral coronary pressure and retrograde flow afterabrupt coronarv artery occlusion; b) correlate these functional indiceswith a quantitative anatomic index of coronarv collateral develop-ment; and c) observe changes in these parameters after repeatedreocclusion of a coronarv arterv.

Materials and MethodsOur studies were made in 14 healthy dogs weighing 20 to 35 kg.' These animals

were trained to lie quietly and unrestrained for seVeral hours on a padded table,before and after surgery. WNe anesthetized the dogs with intravenous sodiumpentobarbital (30 mg kg) and performed a left thoracotom- at the fifth leftinterecstal space while maintaining the animal on intermittent positive pressurebreathing with a Harvard respirator. The heart wvas exposed and supported in apericardial sling. The main branches of the left coronary artery w-ere identifiedand 1.5-cm segments of the left anterior descendens and the left circumflexbranch were dissected free. In 6 dogs, a pneumatic occlusive cuff 12 was placed onthe left circumflex branch. An intracoronan- tube l13 wvas implanted in the leftcircumflex branch distal to the cuff for measuring peripheral coronary, pressure. In8 dogs a pneumatic occlusive cuff 12 was placed on the left anterior descendensbranch and a silastic T-tube 11 inserted into the same branch distal to the cuff.The T-tube allowved continuous coronarv blood flow until the time of occlusion.Then measurements of peripheral coronary pressure and retrograde flow wereobtained from the T-tube. In all animals a polyvinyl catheter was inserted intothe distal aortic arch to obtain aortic blood pressure. These devices were tunneledsubcutaneouslv and attached to appropriate skin connectors.12 Patency of the in-tracoronarv tube was maintained by flushing once or twice daily wsith 20,000 USP

* In conducting the research described, the investigators adhered to the Guide forLaboratorv Animal Facilities and Care as promulgated bh the Committee on the Guidefor Laboratory Animal Facilities and Care of the Institute of Laboratorv Animal Re-sources, National Academy of Science-National Research Council.

Vol. 67, No. 3 CORONARY COLLATERAL CIRCULATION 485June 1972

units ml of heparin; the aortic tube was flushed dailv with 1000 USP units mlof heparin. Fibrinolysin was occasionallv needed to obtain free backflow of blood.Aortic and coronary phasic pressures wrere measured with Elema-Schonandertransducers. Records of phasic pressure were recorded on an Elema-SchonanderMingograf 81 ink-jet recorder. Nfean aortic and coronanr blood pressures weredetermined on a number of representative heart beats bv planimetric integrationusing calibration factors. Tension-time index 14 was equal to the product ofmean systolic aortic pressure during svstolic ejection times the duration of svstoleanid w-as ex-pressed in mm Hg-sec!'beat.Two to three days after recovenr from surgery aortic and coronary pressures

and coronary collateral indices were measured, wvith the dog lying on its rightside. Tw,o methods -ere used to study coronary collateral circulation. First, esti-mates of residual pressure (peripheral coronary pressure) were obtained b-measuring it in the coronarv branch distal to the point of its temporary or per-manent occlusion, using the pneumatic cuff.9 During control runs (ic, beforepermanent vessel occlusion) the peripheral coronary pressure was arbitrarily de-fined as the residual pressure at the end of a 10-second occlusion. Second, retro-grade flow wvas measured from the peripheral end of the anterior descendensbranch 11 bs collecting it for at least 30 seconds in a graduate. After the controlruns in the normal dog, either the circumflex or anterior descendens branch wasoccluded abruptly by the pneumatic cuff for periods of 2 hours to 8 days.Changes in coronary collateral indices during permanent coronar- occlusion weremonitored as frequently as technicallv feasible, usually at 5-to 15-minute intervals.

In 2 dogs, the occlusion was released after 2 hours and coronary collateralindices measured 1 minute later. After 2 days recovery, the 2-hour occlusion,as repeated. This procedure was repeated tvice more. In 1 of these dogs, 24-hour occlusion of the circumflex artery was later repeated in like manner at 4-day intervals.

After the experimental studies were completed, the animals were killed wvithan overdose of sodium pentobarbital, the hearts removed and placed in cold salinein a refrigerator for 24 to 36 hours until rigor mortis subsided.

Gelatin Injection Method

The hearts -.-ere warmed to room temperature, the atria removed and theleft coronary branches cannulated with polyethylene tubing. Both major left cor-onarv branches %vere injected wvith a modified Schlesinger mass, according tothe procedure of NMenick et al.11 After appropriate fixation and clearing, the num-ber and diameters of intercoronary collaterals were recorded and the quantita-tive anatomic anastomotic index determined for each heart, according to Nfenickct al.11 Representative sections were taken from the injected specimen for his-tologic examination.

Results

Systemic and coronarv data before and during coronarv artenrocclusion are summarized in Tables 1 and 2. Due to the complicatednature of the experiments, not all of the desired measurements wereobtained in each dog. Four dogs (7, 9, 10 and 13) developed ventric-ular fibrillation during coronarv artery occlusion. This occurred at 2to 25 hours after the onset of occlusion. Nine days after occlusion car-


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diac arrest occurred immediately after fibrinolvsin wvas injected intothe heart to unplug the silastic intracoronan- tube of dog 12.

Control Data

A typical peripheral coronary pressure tracing is show-n in Text-figure1. This tracing resembles the ventricular pressure wave- ie, a rapidincrease at the beginning of svstole and a rapid decline in the latterhalf of svstole with no runoff during diastole. During the control period,heart rate and aortic blood pressure averaged 122 + 6 beats/min and103 ± 3 mm Hg, respectively. These values are similar to those ob-tained by Pasvk et all5 in the unanesthetized dog. Retrograde flow-sduring the control period averaged 3.0 + 0.3 ml/min. Retrograde flowhas not been measured previously in the intact unanesthetized dog,but this value wvas similar to that obtained by other investigators inthe open chest anesthetized animal.1'

Responses During Coronary Artery OcclusionSystemic and General Changes

At some time wvithin the first few- minutes, and often within the firstminute, after coronar- artery occlusion, heart rate increased. As theocclusion continued, heart rate increased further. The peak rate,varying from 108 to 187 beats/min, wvas reached some 6 to 24 hoursafter the onset of occlusion (Tables 1 aind 2). Aortic pulse pressuredecreased progressively throughout the occlusion period, while meanaortic pressure did not decrease significantly. Tension-time index(Table 2) decreased significantly (P < 0.01) at 1 to 48 hours afterthe start of occlusion and then returned to control levels.

Peripheral Coronary Pressure Changes

WNithin the first few minutes of coronary artery occlusion, meanperipheral coronary pressure rose. A significant increase (P < 0.01) ofmean peripheral coronary pressure occurred within 2 hours of theonset of occlusion (Table 2) and pressure continued to rise through-out the duration of occlusion. At the same time, there was a markedincrease in peripheral coronar- pulse pressure in both its systolic anddiastolic levels. Although mean peripheral coronarx pressure reacheda level that wvas approximatelv 66& of the prevailing aortic bloodpressure during the first 96 hours of coronary artery occlusion, theperipheral coronary pressure trace retained a ventricular pressurewvave form like that show%n in Figure 1. In the 3 dogs (5, 8, 12) oc-cluded for longer than 96 hours, mean peripheral coronary pressure

CORONARY COLLATERAL CIRCULATION

09

Aortic Press(mm Hg)

Peripheral Circulation Pressure(mm Hg)

92120

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.... .....

40

120 46

40

O

TEXT-FIG 1-Phasic tracing from Dog 3 six hours after the onset of coronary oc-

clusion. Traces from top to bottom are time (1-second inter-als), aortic blood pressure(AP) and left circumflex peripheral coronarv pressure (PCP). Mlean values for heartrate, AP and PCP are given in bold numerals. Recording speed = 50 mm/sec.

continued to rise; in dog 5, at 10 days after the onset of occlusion, itwas nearly identical to the prevailing aortic blood pressure (Text-figure 2). A striking alteration of wave form occurred in the peripheralcoronary7 pressure trace when the duration of occlusion exceeded 96hours. The tracing was similar to the aortic pressure trace ie, theappearance of diastolic runoff and a dicrotic notch, and no longerresembled a ventricular pressure curve. These features of the pressure

curve indicate the presence of large intercoronarv collaterals.9

Retrograde Flow Changes

Typical changes obser-ved in retrograde flow before and after cor-

onarv arterv occlusion are showrn in Tables 2 and 3. Control valuesfor retrograde flow averaged 3.0 0.3 ml/min. In the 5 dogs that

developed ventricular fibrillation or cardiac arrest (7, 9, 10, 12 and 13)retrograde flow decreased from control values (Table 3). Dogs 7 and13, which had the lowest control values for retrograde flow, developedventricular -fibrillation the earliest-ie, within 2 hours of the onset of

Vol. 67, No. 3June 1972

Heart Rate(bots/minW

489


HNMrt Re 946 97

90 105

920roAortic Prsuesmao 4-

throgrode flow * 4.3m1/nin Retroorade flow * 6.4.1/mn

p 120r 46 , 903

Clrcuiotion Prssure _(mm N 40 -_ > *->

I y 7 days

Time from Occlusion 8-76

TEXT-FIG 2-Phasic tracing from Dog 5 one day (left panel) and 7 days (right panel)after the onset of coronarv occlusion. Description same as for Text-figure 1. At 7 daysperipheral coronary pressure trace has a wave form similar to the aortic blood pressuretrace.

coronarv artery occlusion. In the remaining 3 dogs, there was nosignificant change in retrograde flow from control values during thefirst 96 hours of occlusion, although mean peripheral coronarv pres-sure rose to high levels. WN'hen the duration of occlusion exceeded96 hours, retrograde flow increased above control levels. Dog 5, oc-cluded for 240 hours, and dog 8, occluded for 120 hours, showed a49 and 19 increase, respectively, in retrograde flow. This rise wassecondarx to an increase in the size and number of intercoronarvcollaterals, since heart rate and mean aortic blood pressure of these2 dogs were not significantlv different from control values (Table 1).

Text-figure 3 shows the changes in collateral indices observed in Dog5 during 8 davs of coronarv artery occlusion. During the initial 24 hoursof occlusion there were rapid rises in heart rate and peripheral coro-narv pressure, while mean aortic blood pressure and retrograde flowwsere unchanged. The tachvcardia persisted for an additional 24 hoursbefore heart rate returned to control values 3 davs after the onset ofocclusion. Peripheral coronary pressure continued to rise throughoutocclusion and was nearly equal to the prevailing aortic blood pressure7 to 8 days after the start of occlusion. BV this time the configurationof the peripheral coronarv pressure wave was similar to that of theaortic pressure wave (Text-figure 2). Retrograde flow remained constantduring the first 4 days of occlusion; on the fifth dav, retrograde flow


began and contintued to rise throughout the remaining observationtimes. The time-interval before retrograde flow began to increase wassimilar to the minimum time interval, indicated by othersi'8 necessarvfor the size or number of intercoronarv anastomoses to increase.

Effects of Repeated Occlusions on Peripheral Coronary Pressure

In dogs 2 and 3, the coronarv arterv was repeatedKv occluded (2 to24 hours duration) to observe effects on collateral indices and on theanastomotic index. In both dogs, peripheral coronarv pressure was thesole collateral index available. Dog 3 was subjected to four 2-hour andtwo 24-hour occlusions with _- to 6-day recoverv intervals. The observeddata are shown in Figures 4 and 5. During the first 2-hour occlusion,peripheral coronarv pressure rose from a control value of 18 to 38 mmHg.Heart rate was unchanged and mean aortic pressure varied during occlu-sion. One minute after the 2-hour occlusion was released, the coronarvarterv was reoccluded for 10 seconds to obtain peripheral coronarv pres-sure. WN-ithin this brief interval, peripheral coronarv pressure fell to thecontrol level and remained there during the 4-dav recoverv interval.During the second 2-hour occlusion, peripheral coronarv pressure roseto a level higher than before, but fell back to the control level 'within 1

160.

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601-

Mon PwWwahr Orcuitim Presu 40 -

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Time from Ocduwoo (days) 8-76

TEXT-FIG 3-Changes in heart rate, retrograde flow-, mean aortic blood pressure andperipheral circumflex pressure observed in dog 5 during the initial 8 days of coronaryocclusion. Control values before occlusion are given for all parameters. Onset of coronaryocclusion was at time 0.

492 BLOOR AND WHITF American Journalof Pathology

minute after the occlusion was released. The maximum rate of riseof peripheral coronar- pressure (mmHg/hr) during occlusion increasedwith repeated occlusion (Text-figure 4). WN7hen repeated occlusions werelonger (24 hours), similar results occurred (Text-figure a3). Control val-ues for peripheral coronary pressure were the same as before (15-18mmHg). WA-ith the longer duration of occlusion, peripheral coronarvpressure increased to higher levels, approximating 77 to 90, of prevail-ing aortic blood pressure. The maximum rate of rise of peripheral cor-onarv pressure wvas greater during the second 24-hour occlusion. Asurprising finding wNas the fall of peripheral coronary pressure to con-trol level within 1 minute after the 24-hour occlusion w-as released.After the second 24-hour occlusion it was maintained and the dogkilled with an overdose of sodium pentobarbital. Postmortem studies(Table 4) showed that the repeated peripheral coronar- pressure risesin dogs 2 and 3 wvere not associated with an increase in the size ornumber of intercoronarv anastomoses.

Postmortem Studies (Anastomotic Indices)

The distribution of coronary collaterals in each heart is given inTable 4. In dogs occluded for less than 96 hours, the ranges of values

1-44I-69--- 5-445-69--I 4-17-69-- -4-19-69 --1

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Time from Occimsoo (haws) B-40

TEXT-FIG 4-Changes in heart rate, mean aortic blood pressure and peripheral cir-cumflex pressure observed in dog 3 during four repeated 2-hour occlusions of the leftcircumflex coronary artery. Control values before each occlusion are given for allparameters. Onset of each occlusion was at time 0. Recoverv values for all parameterswere obtained 1 minute after the release of coronarv occlusion.


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120Mom Aortic Pressure

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Maximnwm PCP Rise so L 31 l

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(man Hg) _L_A_A_O 0 8 16 24 - O 0 8 16 24Z, . Z

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TEXT-FIG 5-Changes in heart rate, mean aortic blood pressure and peripheral cir-cumflex pressure observed in dog 3 during two repeated 24-hour occlusions of the leftcircumflex arterv. Description same as for Text-figure 4.

for anastomotic indices of coronarv collateral development were simi-lar to those observed before.1' The average value for this group (dogs1-4, 6, 7, 9-11, 13 and 14 ) wvas 909 ± 1.34. Dogs 5, 8 and 12 ,wrhich wereoccluded for longer than 96 hours, had higher anastomotic indices,ranging from 2275 to 3994. Their average value (2915 ± 543) wassignificantly greater (P < 0.001) than that for the other group, indi-cating that coronarv occlusion lasting more than 96 hours leads to anincrease in the size and number of intercoronarv collaterals.

Figures 6 and 7 demonstrate gelatin injection specimens from arepresentative dog from each occlusion group. Dog 3 (Figure 1) hadrepeated occlusions of the coronarv arter-, but never for more than 24hours at any one time. Although its peripheral coronarv pressure roseto high levels on several occasions (Text-figure 4 and 5), relatively fewintercoronar-v collateral vessels were present. Those present were smallin size-ie, one-half of them were less than 100 It in diameter (Table4). In dog 5 the left circumflex coronar wvas occluded for 240hours. Peripheral coronary pressure rose to levels approximating theprevailing aortic blood pressure, while a significant increase in retro-grade flowv occurred after 96 hours of coronar- occlusion. The gelatinspecimen from dog 5 (Figure 2) had an increased number of inter-

494 BLOOR AND WHITE

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Table 4-Incidence and Size of Intercoronary Collaterals

Size of intercoronary collaterals*Duration of Anastomotic

Dog No. occlusion (hr) 40100 100-200M 200-300,A index

1 1 3 4 8 12192 72 8 6 3 8753 24 4 3 1 5004 2 8 3 - 3505 240 7 15 14 39946 1 9 4 - 4567 4 14 5 3 11128 120 10 5 11 24759 25 10 10 4 1763

10 70 10 7 - 76211 4 24 8 3 146912 216 4 12 6 227513 2 16 5 - 60014 2 18 6 1 888

* Values represent the number of anastomotic connections in each size category betweenleft anterior descending and left circumflex coronary arteries.

coronary collaterals, 39W of w%hich w-ere greater than 200 It in diam-eter. These wvere located predominantly in the epicardial surface,although some were located w%ithin the midportions of the mvocar-dium. In either instance, their morphologic characteristics suggestedthat they represented physical expansion of preexisting vessels-ie,thin walls and large lumens with the absence of mitoses in the vesselwalls.

Discussion

This study was undertaken to detect the rapidity- with which coronarycollateral circulation developed after abrupt coronary artery occlusion.In previous studies in unanesthetized animals coronary occlusion wasgradual 915'1-6 or only peripheral coronary pressure observed 91l15,16wvithout correlating phvsiologic indices with morphologic indices. In ourstudy, an anastomotic index of coronary, collateral circulation establishedin this laboratorv " was correlated with both peripheral coronary pres-sure and retrograde flow.Although we know of no method for measuring collateral flow through

a coronary bed directly, the physiologic indices wve used are thought torepresent the functional state of coronary collateral connections.9 .10.17However, the discrepancies bet-ween changes in peripheral coronarvpressure and retrograde flow during the initial 24 to 48 hours after ab-rupt coronary occlusion suggest that peripheral coronary pressure has


limitations as an index of collateral development during this period. Ourfindings of a rapid rise in peripheral coronary pressure w-ith retention ofa ventricular pressure wave form after abrupt coronar- occlusion, par-ticularlv on repeated occlusion, are in agreement with those of Pasvket al 1 and Khouri et al.' However, in all instances, in ouir study w-henocclusion was maintained for less than 96 hours, the size or number ofintercoronarv anastomoses did not increase (Table 4). Since the afore-mentioned studies 9"'1l did not conduct similar postmortem injectionstudies, one must have reservations about the interpretations offered.Our results indicate that change in peripheral coronar- pressure duringthe initial 24 to 48 hours of abrupt coronary occlusion is a poor index ofchanges in the anatomic development of coronary collateral circulation.The insensitivity of peripheral coronary pressure as an index of collateralblood flow after abrupt coronary occlusion has been wvell documented bySchaper.'"The rapid rise in peripheral coronary pressuire after the onset of

coronary occlusion may reflect other changes. For example, after theonset of coronaryocclusion, the ischemic mvocardium, wvhich containsthe collateral channels that transmit the peripheral coronary pressurepulse, ceases to contract and bulge."9 As time passes, it regains con-tractile function anid slowly increases its contractilitv.2'22 Since thecollateral channels initiallv are small, peripheral coronary pressuremay largely reflect effects of extravascular compression on collateralchannels. Thus, w%hen the ischemic mvocardium reaches its minimumcontractile level immediately after occlusion,22 peripheral coronarypressure is lowv. As contractility of the ischemic mvocardium increases,extravascular compression of collateral channels w-ould increase andperipheral coronarv pressure would rise. If the collateral channels re-mained small, the -entricular wave form would be retained. Thus, thewave form change of peripheral coronarv pressure to that resemblingthe aortic pressure wave would occur wvhen the intercoronarv col-laterals increased in size. This is consistent with our findings and wviththe earlier study by Elliot et al.9Our observation of the rapid regression of peripheral coronarv pres-

sure to control level after the occlusion is released, and its rapid rise onreocclusion resembles the observations of Khouri et al.10 Howvever, ifperipheral coronarv pressure is an insensitive index of collateral bloodflow in this situation,'8 peripheral coronarv pressure changes probablydo not represent changes in the functional status of coronarv collateralchannels, as Khouri et al 10 suggest. Rather, it may reflect changes in thecontractilitv of that part of the mvocardium made ischemic by occlu-sion. '


Retrograde flow- is an indirect index of perftusion flow since it iscollected against atmospheric pressture and -ithouit the normally sup-plied impedance of the bed. However, our previous studv show-ed alinear relationship betwveen retrograde flow- and a quantitative ana-tomic anastomotic index.11 Our present findings that there w-as no changein retrograde flow during the initial 96 hours of occlusion, associatedw-ith the lack of significant increase in the size or number of inter-coronar- collaterals, suggest that retrograde flow is a better index thanperipheral coronary pressure for determining the functional stattus ofthe coronary collateral circulation due to its anatomic development.

In our experiments, changes in retrograde flo- and anastomoticindex after abrupt closure of a major coronary branch in the unanes-thetized dog did not occur until more than 96 hours of occlusion hadpassed, contrary to the suggestion by Pasvk et all' that coronarv collat-eral fuinction improves during the first 24 to .34 hours of coronaryocclusion. Our findings are in agreement with the isotope studies byRees and Redding,5 the physiologic sttudies by several investigators 1and the morphologic studies by Blumgart, Zoll et al.'8 The expen-mental model used in our study demonstrates the feasibility of combin-ing physiologic and morphologic approaches to determine coronarycollateral development. Extension of this approach to determinewN-hether coronar- collaterals, once formed, regress or reappear, andxvhat interventions affect their development, seems appropriate.

References1. Eckstein RWV: Coronarv interarterial anastomoses in young pigs and mon-

grel dogs. Circ Res 2:460-465, 1954. Gregg DE, Thomton JJ, 'Mautz FR: Magnitude. adequacy and source

of the collateral blood flow and pressure in chronicallv occluded coronarvarteries. Am J Phb siol 127:161-17-4, 1939

3. Haft JI, Damato AN: 'Measurement of collateral blood flow after mvo-cardial infarction in the closed-chest dog. An Heart J i7:641-648, 1969

4. Johansson B, Linder E, Seeman T: Collateral blood flow in the mvo-cardium of dogs measured with krvpton 1. Acta Ph-siol Scand 62:26.3-270.1964

5. Rees JR, Redding VJ: Anastomotic blood flows in experimental myocardialinfarction. Cardiovasc Res 1:169-17-8, 1967

6. Zoll PM, Norman LR: Effect of v-asomotor drugs and of anemia uponinterarterial coronary anastomoses. Circulation 6:832-842, 1952

7 Paul MIH, Norman LR, Zoll P'M, Blumgart HL: Stimulation of inter-arterial coronarv anastomoses by experimental acute coronary occlusion.Circulation 16:608-614, 1957

8. Blumgart HL, Zoll P'M, Freedberg AS, Gilligan DR: The experimeintalproduction of intercoronary arterial anastomoses and their functioinal sia-nificance. Circulation 1:10-27, 1950


9. Elliot EC, Jones EL. Bloor CMf, Leon AS. Gregg DE: Day-to-day changesin coronarv hemodynamics secondary to constriction of circumflex branchof left coronary artery in conscious dogs. Circ Res 2:237-250, 1968

10. Khouri E'M, Gregg DE, Lowensohn HS: Flow in the major branches of theleft coronarv artery during experimental coronary insufficiency in the un-anesthetized dog. Circ Res 23:99-109, 1968

11. Islenick Fl, White FC, Bloor C'M: Coronary collateral circulation: De-termination of an anatomical anastomotic index of functional collateral flowcapacity. Am Heart J 82:503-510, 1971

12. Sham GB, WN'hite FC, Bloor CM: A constrictive and occlusive cuff formedium and large blood vessels. J Appl Pysiol 28:510-512, 1970

13. Herd JA, Barger AC: Simplified techniques for chronic catheterizationof blood vessels. J Appl Physiol 19:791-793, 1964

14. Sarnoff SJ, Braunwald E, WN'elch GH, Jr, Case RB, Stainsbv WN, Cruz R:Hemodvnamic determinants of oxygen-consumption of the heart X ith specialreference to the tension-time index. Am J Physiol 192:148-156, 1958

15. Khouri EM, Gregg DE, 'McGranahan GM, Jr: Regression and reappear-ance of coronary collaterals. Arn J Physiol 220:655-661, 1971

16. Elliot EC, Bloor CM, Jones EL, 'Mitchell WN'J, Gregg DE: Effect of con-trolled coronary occlusion on collateral circulation in conscious dogs. Arn JPh-siol _0::857-861, 1971

17. Pasvk S, Bloor C'M, Khouri EM, Gregg DE: Systemic and coronary effectsof coronarv arten- occlusion in the unanesthetized dog. Am J Physiol220:646-.654, 197i

18. Schaper WV: The Collateral Circulation of the Heart. Amsterdam, North-Holland Publishing Company, 1971

19. Tennant R, WN'iggers CJ: The effect of coronary occlusion on mvocardialcontraction. Am J Physiol 112:351-361, 1935

20. Hood WVB, Jr: Experimental mvocardial infarction. III. Recovery of leftventricular function in the healing phase. Contribution of increased fibershortening in noninfarcted mvocardium. Am Heart J 79:531-538, 1970

21. Kumar R, Hood WN'B, Jr, Joison J, Norman JC, Abelmann WVH: Experi-mental mrnocardial infarction. II. Acute depression and subsequent recoveryof left ventricular function: serial measurements in intact conscious dogs. JClin Invest 49:55-62, 1970

22. Schelbert HR, Covel JW\, Bums JWN', 'Maroko PR, Ross J Jr: Obseryationson factors affecting local forces in the left ventricular wall during acutemvocardial ischemia. Circ Res 29:306-316, 1971

AcknowledgmentsThe authors are deeply grateful to Mr. Ben N. Corpuz for his expert technical

assistance.

Fig lA-Macrophotograph of gelatin injected specimen from dog 3. Posterolateralview of heart shows the posterior descending circumflex artery coursing toward theapex (bottom). At the margin between the terminal branches of the anterior descend-ing and circumflex branches (arrows) no intercoronary anastomoses are visible (x 1).B-High power view of same specimen at the margin between terminal brances of theleft anterior descending branch (LAD) and the left circumflex branch (right margin).An occasional intercoronary collateral (arrow) less than 100 ui in diameter is present(x 10).

A

B

Fig 2-Macrophotograph of gelatin injected specimen from Dog 5. Anterolateralview of heart shows the left anterior descending branch (LAD) coursing towardthe apex (bottom). Along the lateral margin of the heart several large intercoronarycollaterals (arrows) are present on the epicardial surface, joining terminal branchesof the anterior descending and circumflex vascular beds (x 1).

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Functional Development Coronary Collateral Circulation