Distribution of Coronary Blood Flow During Cardiopulmonary Bypass in Pigs

Distribution of Coronary Blood Flow During Cardiopulmonary Bypass in Pigs Possible Implications for Left Ventricular Hemorrhagic Necrosis

Ronald M. Becker, M.D., Harry M. Shizgal, M.D., and Anthony R. C. Dobell, M.D.

ABSTRACT The distribution of coronary blood flow during cardiopulmonary bypass in pigs was estimated by the radioactive microsphere method. Total flows during bypass were inadequate or marginal under the conditions of the experiment. The endocardia1 side of the myocardium was markedly underper- fused when the heart remained in ventricular fibrillation during bypass. Vasodilation (with dipyridamole) or perfusion with a pulsatile pump improved the gradient, although distribution still greatly favored the epicardial side. Only when the heart remained in normal sinus rhythm during bypass was the normal distribution maintained. The implications of these experiments for explaining the lesion of left ventricular hemorrhagic necrosis are discussed.

ecent reports have highlighted the lesion of left ventricular hemorrhagic necrosis as a major contributor to morbidity and R mortality following cardiopulmonary bypass [9, 191. The patho-

genesis of this lesion remains obscure. Based on the hypothesis that the lesion is ischemic in nature, we used the radioactive microsphere technique to study the distribution of coronary flow to the free wall of the left ventricle before and during bypass in pigs.

Materials and Met hods OPERATIVE TECHNIQUE

Poland-China pigs weighing 20 to 25 kg. were anesthetized with a nitrous oxide, oxygen, and curare mixture [3]. Bilateral thoracotomy through the second intercostal space was used to expose the heart and great vessels. Cardiopulmonary bypass was instituted in the usual manner following cannulation of the ascending aorta through the brachiocephalic artery and of the inferior vena cava through the right atrium. The superior vena cava was drained by side holes in the inferior vena cava cannula so that bypass was total. The pericardium was opened only enough to allow for

From the Departments of Surgery, Royal Victoria Hospital and McCill Univrrsity,

Supported by a grant from the Medical Research Council of Canada. Presented at the Ninth Annual Meeting of T h e Society of Thoracic Surgeons. Houston,

Address reprint requests to Dr. Dobell, Department of Surgery, Royal Victori;i Houpitnl,

Montreal, Que., Canada.

Tex., Jan. 22-24, 1973.

Montreal 112, Que., Canada.

228 THE ANNALS OF TUORACIC SURGERY

Distribution of Coronary Flow During Bypass

caval cannulation. Because the pericardium over both ventricles was left intact, the left ventricle was not vented, since others [l] have shown that venting is unnecessary when the pericardium remains intact. Except for the pump (described below), the extracorporeal system was the same in all instances and included a Temptrol Pediatric Q-110 oxygenator.* The oxygenator was primed with 1,500 ml. of lactated Ringer's solution containing 20 mEq. KC1 and 89.2 mEq. NaHC03 in all instances. Temperature was not controlled during these experiments, so perfusion was at or close to normothermia. Maximum flow consistent with a minimum blood level in the oxygenator was used in all experiments. No attempts were made to improve flow by means of additional fluid or drugs, and it is probably of considerable significance that the flow in these experiments was below the acceptable range. In other words all organs, including the heart, were offered less than adequate blood flow.

ESTIMATION OF DISTRIBUTION OF CORONARY FLOW

Radioactive microspherest that were 15 * 5 p in diameter and labeled with chromium 51 or ytterbium 169 were used to estimate the distribution of coronary blood flow. One label was injected directly into the left atrium just prior to the onset of bypass with the heart beating normally. The other label was injected at 45 minutes of bypass into the arterial line emerging from the pump. Each injection of Cr 51 was approximately 10 pCi while that of Yb 169 was 2 pCi to allow for optimal separation of counts due to each isotope (Yb 169 being 8.5 times more active than Cr 51). Following the second injection, the heart was excised: the free wall of the left ventricle was cut free, washed of blood, and fixed overnight in 10% formalin. It was then cut by hand into three slices of myocardium: endocardia1 (endo), midmyocardial (mid), and epicardial (epi). Each section was placed in tared test tubes, dried for 48 hours at 90°C., and then weighed. Radioactivity in each portion was then determined by counting$ at windows of 50 to 300 and 275 to 350 kiloelectron volts (kev.) according to well-known methods of differential gamma spectrometry [23]. Counts due to each isotope for each portion of myocardium were separated by computer,§ and the results were expressed as counts per minutes per gram dry weight. The ratios of mid/endo or epi/endo activities were then determined.

GROUPS OF ANIMALS There were five groups of 5 animals each: in the first four groups a roller

pump was used.7 (1) In the control group the hearts remained in ventricular

*Bentley Laboratories, Inc., Santa Ana, Calif. t3M Company, St. Paul, Minn. tPackard Gamma Spectrophotometer, model 3575, Hewlitt-Packard Co., Montreal, Que.,

SPDP-11, Digital Corp., Montreal, Que., Canada. YSarns Inc., Ann Arbor, Mich.

Canada.

VOL. 16, NO. 3, SEPTEMBER, 1973 229

BECKER, SHIZGAL, AND DOBELL

TABLE 1 . MEAN BLOOD FLOWS DURING CARDIOPULMONARY BYPASS I N FIVE GROUPS OF ANIMALS"

Flow Group Rhythm Pump Other (ml. /min./kg.)

1 Ventricular fibrillation Nonpulsatile . . . 11.8 * 1.8 2 Normal sinus Nonpulsatile . . . 22.6 k 4.9 3 Ventricular fibrillation Nonpulsatile Dipyridamole 29.6 f 5.8 4 Ventricular fibrillation Nonpulsatile Dipyridamoleb 13.2 -+ 1.4 5 Ventricular fibrillation Pulsatile . . . 9.8 r+. 3.8 "As determined by calibration of the pumps f 1 standard error. "Flow intentionally diminished by reducing the number of revolutions per minute of the

roller pump.

fibrillation for the duration of bypass. It should be noted that fibrillation was not induced, but rather the animals fibrillated spontaneously immediately after institution of bypass. (2) In the NSR group, immediately after institution of bypass the heart was defibrillated and thereafter remained in normal sinus rhythm. (3) In the Persantine high-flow group, dipyridamole (Persantine"), 10 mg. per kilogram of body weight, was added to the oxygenator prime. Dipyridamole is a potent coronary vasodilator and also increases flow on bypass [4]; this group therefore tested the combined effect of coronary vasodilation and increased flow on bypass. (4) In the Persantine low-flow group, Persantine, 10 mg. per kilogram of body weight, was again added to the prime, but flows were reduced to levels comparable with those in Group 1. This group therefore tested only the effect of coronary vasodilation. ( 5 ) In the pulsatile flow group the Sarns roller pump was replaced with a pulsatile pump designed in this laboratory [SO]. As in Groups 1, 3, and 4, the heart remained in ventricular fibrillation for the duration of bypass.

STATISTICAL ANALYSES

Probabilities for differences among the five groups of pigs were determined from the F values of analysis of variance. Prebypass and postbypass values within each group were compared by the two-sample unpaired t test. Differences from unity of the ratios of mid/endo or epiiendo activity were determined by the one-sample t test.

Results The drainage to the pump oxygenator system was twice as great when

the heart was in sinus rhythm as when it remained in ventricular fibrillation, as shown in Table 1. This was a consistent finding, and we intend to pursue the ramifications of this observation further. We do not believe it inv a I'd 1 ates the data on blood flow distribution to be presented 1)elow. The flow distributions in Groups 3 and 4 were approximately equal; the only variable

'Persantine (Geigy Pharmacenticals. Ardsley, N.Y.) was kindly supplied by Dr. G . H. Worsley of Rochringcr-Ingelheim, Montreal, Qw., Canada.

230 THE ANNAIS OF THORACIC SURGERY


TABLE 2. DISTRIBUTION OF CORONARY FLOW PRIOR T O CARDIOPULMONARY BYPASS IN FIVE GROUPS OF ANIMALS

Coronary Flow Ratio Group MidIEndo" Epi/Endob

1 0.92 rf: 0.04 0.73 k 0.04 2 0.97 k 0.05 0.76 rf: 0.05 3 0.91 rf: 0.03 0.73 rt 0.04 4 0.84 k 0.04 0.69 k 0.06 5 0.91 k 0.08 0.64 2 0.06

"Ratio counts per minute per gram of midmyocardial to endocardial side of free wall of

bRatio counts per minute per gram of epicardial to endocardial side of free wall of left left ventricle 1 standard error.

ventricle 2 1 standard error.

between these two groups was the difference in total flow on bypass, and this difference was comparable to that between Groups 1 and 2. Flows in Group 5 animals (pulsatile pump) actually were poorer than the mean would indicate due to a valve which functioned properly in only one experiment. Nevertheless, as emphasized again by comparison of Group 3 and 4 animals, large differences in total flow seemed to alter distribution of coronary flow little. It is recognized that these flows are inadequate to sustain life, but these were the maximum flows possible under the conditions of the experiment. We have recognized in previous experiments the extreme difficulty in the pig of maintaining adequate blood flows during bypass. This was undoubtedly due partially to the nonblood prime used in our experiments. Previous experiments also have suggested to us that microthrombosis and platelet microemboli may additionally be partially responsible for the inadequate blood flow [4].

DISTRIBUTION OF CORONARY FLOW PRIOR TO BYPASS Table 2 shows the distribution of coronary flow for the five groups of

animals prior to cardiopulmonary bypass (CPB). gradient of activity so that the endocardial side determined by analysis of variance there was ( p > 0.05 for all groups) in pre-CPB distribution all groups the epi/endo ratio of activity per significantly ( p < 0.01) less than unity.

In all groups there was a was the best perfused; as no significant difference

among the five groups. In gram of dry weight was

DISTRIBUTION OF CORONARY FLOW ON BYPASS In Table 3 the distribution of coronary flow at 45 minutes of CPB is

shown. Comments on the various groups follow. Group 1 . In contrast to the pre-CPB condition, there was a gradient of

activity which greatly favored the epicardial side when the heart was in ventricular fibrillation on CPB.

When the heart remained in sinus rhythm, the gradient favoring the endocardial side was maintained. The difference of distribution of flow from the pre-CPB situation was not significant ( p > 0.10).

Group 2.



TABLE 3. DISTRIBUTION OF CORONARY FLOW AT 45 MINUTES OF CARDIOPULMONARY BYPASS IN FIVE GROUPS OF ANIMALS

Coronary Flow Ratio Group Mid/Endo" Epi/Endob

8.17 2 1.44 1.09 k 0 . 0 3 3.25 & 1.12 2.78 f 0.35 2.01 e 0.40

17.60 2 4.37 0.88 k 0.09 5.03 2 2.80 5.19 f 1.14 3.12 t 1.55

"Ratio counts per minute per gram of midmyocardial to endocardial side of free wall of

bRatio counts per minute per gram of epicardial to endocardial side of free wall of left left ventricle 2 1 standard error.

ventricle t 1 standard error.

Group 3. With dipyridamole in the prime, the distribution of flow was significantly improved ( p < 0.01 for difference from Group l), but obviously it remained poor.

Group 4 . Under the same conditions as for Group 3 except that the mean flow was less than half that in Group 3, the distribution of flow did not significantly change.

When pulsatile perfusion was used, the distribution of flow was greatly improved. In 4 animals the epi/endo ratio was less than 2; an epi/endo ratio of 10.30 in the fifth animal accounts for the high mean value and large standard error.

Group 5.

Comment The technique of measuring distribution of flow by radioactive

microspheres is well established. The technique was introduced in 1947 by Prinzmetal and his associates [21] and has since been used to estimate distribution of flow in a wide variety of organs and situations. The validity of the technique has been demonstrated by independent methods [15, 22-24, 281.

DISTRIBUTION OF FLOW PRIOR T O BYPASS

We have shown that the distribution of coronary flow under anesthesia and after thoracotomy in the pig favors the endocardial side of the myocardium (see Table 2). Similar results were obtained by others using microspheres [2, 111 or other techniques [13, 16, 171. A teleological explanation for this phenomenon is not readily apparent. It may involve dynamic control of regional vascular supply by myocardial contraction, which produces a gradient in intramyocardial tension [2]; the fact that the vessels supplying the endocardium are of a different nature from those supplying the outer layers [12]; or the increased metabolic demands of the endocardial side [5].

2 3 2 THE ANNALS OF THORACIC SURGERY


DISTRIBUTION OF FLOW ON CPB In contrast to the base-line (pre-CPB) situation, the gradient of flow on

CPB greatly favored the epicardial side whenever the heart remained in ventricular fibrillation (see Table 3). When the heart remained in sinus rhythm, the gradient favoring the endocardium was maintained; pulsatile flow greatly improved the distribution of flow when compared with that achieved by nonpulsatile flow (Group 5 versus Group 1). Propranolol, which decreases intramyocardial wall tension, leads to a preferential shift of flow toward the endocardium [Z, 181. These facts favor the theory that intramyocardial tension is an important determinant of coronary flow distribution. When the heart is beating, intramyocardial pressure converts nonpulsatile aortic flow to pulsatile coronary perfusion because of the rhythmic change in resistance; in the nonbeating heart, nonpulsatile flow remains so [29]. Buckberg [6] has also reported preliminary results demonstrating ischemic damage in fibrillated hearts as opposed to beating, nonworking hearts.

Others have found that endocardial perfusion suffers in other pathological states. Acute left ventricular hypertension [7, 181, acute ischemia [2, 11, 13, 181, and reduced perfusion pressure [18] all produce relative ischemia of the endocardium. It is conceivable that one or more of these factors was responsible for the flow distributions in our experiments. Left ventricular hypertension should not occur when the pericardium over the ventricle is intact, even without a vent [l]. Acute ischemia and reduced perfusion pressure were features of all the experiments and would not account for the differences in flow distributions between groups. For example, poor perfusion pressure and ischemia would be expected to be greater factors in Group 2 than in Group 3, but flow distributions were better in Group 2. In a left-heart bypass preparation in calves, Utley [27] demonstrated a redistribution of flow away from the endocardium which became more pronounced with time on bypass.

Previous experiments have also demonstrated that Persantine favors a preferential shift of flow toward the endocardium [18]. While this may show the vasodilation effect of Persantine, it may also reflect decreased platelet microthrombosis in the sluggish endocardial microcirculation, as we have previously concluded that Persantine in the doses used is effective in preventing platelet microthrombosis in CPB [4]. The finding that intermittent flushing of the coronary arteries with a balanced electrolyte solution may decrease the incidence of subendocardial ischemia may be pertinent in this regard [14]. The effect of Persantine did not seem to be due to increased total flow on CPB, as distributions in Groups 3 (high flow) and 4 (low flow) were comparable. Coronary vasodilation with nitroglycerin also improves relative endocardial flow [Z].



LEFT VENTRICULAR HEMORRHAGIC NECROSIS

This lesion, well described by Najafi and his colleagues [19], involves circumferential necrosis of the inner third of the left ventricle following CPB. The diagnosis is pathological and requires transverse sectioning of the left ventricle; it is unlikely to be noted unless the pathologist is specifically looking for it, which accounts for the general lack of recognition of the lesion. The clinical manifestation is the so-called low-output syndrome [ 19, 261 that requires pump support in the operating room or drug support in the recovery room, and this syndrome is certainly recognized in every cardiac surgery center. In a recent series, left ventricular hemorrhagic necrosis (LVHN) was the single most common cause of hospital deaths following CPB [9]. However, the lesion is undoubtedly not always fatal; Buckberg and co-workers [8] believed that with histochemical techniques they could demonstrate LVHN in 18 of 20 patients dying after CPB, not all of whom died of LVHN.

In a review of our recent deaths following CPB, all 10 patients with LVHN proved at postmortem examination had had fibrillation during CPB. In the series of Najafi and colleagues 1191, 28 of 31 patients fibrillated during CPB. The implication that LVHN is related to fibrillation is obvious, but since fibrillation occurs in many patients who do not appear to develop the lesion and since LVHN develops in the absence of fibrillation, other factors must be involved. It is also likely that perfusion imbalances during bypass would precipitate ventricular fibrillation, and not necessarily the reverse.

A second major factor in the development of LVHN may be left ventricular hypertrophy (LVH). In the study by Estes and co-workers [ 121, the class B vessels (which supply the inner myocardium) did not fill beyond the junction of the middle and inner thirds of the myocardium in a patient with long-standing hypertension. Taber [25] also noted inadequate B vessels in patients with LVH. The majority of reported patients with LVHN have had aortic valve disease [lo, 19, 261, and 58 of GO collected patients had LVH [lo, 19, 261. We have seen hemorrhagic necrosis only once in the right ventricle: the patient had tetralogy of Fallot and consequent right ventricular hypertrophy. Others have also noted that right ventricular hypertrophy predisposes to right ventricular necrosis [8].

On the basis of these facts and our own experiments, we postulate that the lesion of LVHN is basically ischemic in nature. It is predisposed to by ventricular hypertrophy, which produces a relative paucity of endocardia1 vasculature [12, 20, 251, and is further aggravated by ventricular fibrillation, which diverts flow to the epicardium in the face of continuing metabolic demands. In an occasional patient with LVH who is not fibrillating during CPB, other factors may contribute to LVHN. In the series of Najafi and colleagues [19], for example, of the 3 of 31 patients who remained in normal sinus rhythm, 1 had CPB exceeding 7 hours. When the lesion occurs in the

234 THE ANNALS OF THORACIC SURGERY


absence of LVH, fibrillation may be the major culprit, especially when total coronary flow is inadequately maintained. For example, we have seen LVHN after aortocoronary bypass grafting for ischemic disease, in which endocardial vasculature is increased [12]; these patients were all electively fibrillated as a technical aid to the procedure.

CLINICAL IMPLICATIONS

The major implication of the present study is that fibrillation under the conditions of CPB may not be an innocuous procedure, at least not when total coronary flow is less than optimal. When elective fibrillation is used, the heart should be converted to normal sinus rhythm as soon as possible; waiting until the termination of CPB to defibrillate increases endocardial isihemic time. More study is necessary to determine whether ischemic cardiac arrest has an advantage over fibrillation in terms of myocardial metabolic demands. In patients with severe LVH, some protection of the endocardium may be achieved with the use of pulsatile coronary perfusion and perhaps with drugs. Clearly, although patients with LVH are predisposed to LVHN, the implications extend to all patients undergoing CPB. Since total coronary flow during these experiments must have been marginal at best, further experiments are necessary to determine whether endocardial flow suffers even when total flow appears adequate.

LIMITATIONS OF THE STUDY

The major limitation in the present study is the fact that flows achieved on CPB were inadequate. Although in our study total flow on CPB did not seem to alter flow distribution, others [Z, 11, 13, 181 have noted that ischemia and decreased perfusion pressure do produce relative underperfu- sion of the endocardial side. We hope to repeat the experiment with flows more comparable to those in the clinical situation. We also hope to determine the effect of the duration of bypass with a multiple isotope technique and to use the implications of these studies to produce LVHN. Najafi and associates [ZO] and Buckberg and co-workers [8] also implicated reduced perfusion pressures in the pathogenesis of LVHN. This factor is also amenable to study with the microsphere method. It is presumed that the findings in pigs may be extended to human beings; perhaps other techniques of measuring distribution of flow could be safely adapted to the study of myocardial biopsy specimens in human patients on bypass.

References 1. Baird, R. J., de la Rocha, A. G., Miyagishima, R. T., Tutassaura, H.,

Wilson, D. R., Evans, D., and Beanlands, D. S. Assisted circulation following myocardial infarction. Can. Med. Assoc. J . 107:287, 1972.

2. Becker, L. C., Fortruih, N. J., and Pitt, B. Effect of ischemia and antianginal drugs on the distribution of radioactive microspheres in the canine left ventricle. Czrc. Res. 28:263, 1971.

VOL. 16, NO. 3, SEPTEMBER, 1973 Z 3 5


3. Becker, R. M., Lord, L., and Dobell, A. R. C . Techniques and pitfalls of anesthesia and thoracic surgery in the pig. J. Surg. Res. 13:215, 1972.

4. Becker, R. M., Smith, M. R., and Dobell, A. R. C. Effect of platelet inhibition on platelet phenomena in cardiopulmonary bypass in pigs. Surg. Forum 23:169, 1972.

5. Brantigan, J. W., Perna, A. M., Gardner, T. J., and Gott, V. L. Intra- myocardial gas tensions in the canine heart during anoxic cardiac arrest. Surg. Gynecol. Obstet. 134:67, 1972.

6. Buckberg, G. D. In discussion of G. D. Buckberg et al. [8]. 7. Buckberg, G. D., Archie, J. P., Fixler, D. E., and Hoffman, J. I. E. Experi-

mental subendocardial ischemia during left ventricular hypertension. Surg. Forum 22:124, 1971.

8. Buckberg, G. D., Towers, B., Paglia, D. E., Mulder, D. G., and Maloney, J. V. Subendocardial ischemia after cardiopulmonary bypass. J. Thorac. Cardiouasc. Surg. 64:669, 1972.

9. Colapinto, N. D., and Silver, M. D. Prosthetic heart valve replacement. J. Thorac. Cardiouasc. Surg. 61 :938, 1971.

10. Cooley, D. A., Reul, G. J., and Wukasch, D. C. Ischemic contracture of the heart: “Stone heart.” Am. J. Cardiol. 29:575, 1972.

11. Domeneck, R. J., Hoffman, J. I., Noble, M. J., Saunders, K. B., Henson, J. R., and Subijanto, S. Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs. Circ. Res. 25:581, 1969.

12. Estes, E. H., Jr., Entman, M. L., Dixon, H. B., and Hackel, D. B. Vascular supply of the left ventricular wall: Anatomic observations, plus a hypothesis regarding acute events in coronary artery disease. Am. Heart J. 71:58, 1966.

13. Griggs, D. M., Jr., and Nakamura, Y. Effect of coronary constriction on myocardial distribution of Iodo-antipyrine-1-131. Am. J. Physiol. 215: 1082, 1968.

14. Iyengar, S. R. K., Ramchand, S., Charrette, E. J. P., and Lynn, R. B. An experimental study of subendocardial hemorrhagic necrosis after anoxic cardiac arrest. Ann. Thorac. Surg. 13:214, 1972.

15. Kaihara, S., van Heerden, P. D., Migita, T., and Wagner, H. N., Jr. Measurement of distribution of cardiac output. J. Afifil. Physiol. 25:696, 1968.

16. Kirk, E. S., and Horig, C. R. Nonuniform distribution of blood flow and gradients of oxygen tension within the heart. Am. J. Phystol. 207:661, 1964.

17. Love, W. D., and Burch, G. E. Differences in the rate of Rb-86 uptake by several regions of the myocardium of control dogs and dogs receiving L- norepinephrine or pitressin. J. Clin. Invest. 36:479, 1957.

18. Moir, T. W., and de Bra, D. W. Effect of left ventricular hypertension, ischemia and vasoactive drugs on the myocardial distribution of coronary flow. Circ. Res. 21:65, 1967.

19. Najafi, H., Henson, D., Dye, W. S., Javid, H., Hunter, J. A., Callaghan, R., Eisenstein, R., and Julian, 0. C. Left ventricular hemorrhagic necrosis. Ann. Thorac. Surg. 7:550, 1969.

20. Najafi, H., Lal, R., Khalili, M., Serry, C., Rogers, A., and Haklin, M. Left ventricular hemorrhagic necrosis. Ann. Thorac. Surg. 12:400, 1971.

21. Prinzmetal, M., Simkin, B., Bergman, H., and Kruger, H. Studies on the coronary circulation: 11. The collateral circulation of the normal human heart by coronary perfusion with radioactive erythrocytes and glass spheres. Am. Heart J. 33:420, 1947.

22. Racifi, A., Greenfield, A. J., Skinner, D. B., Newman, M. H., and Rutherford, R. B. Organ blood flow measured by radionuclide-labeled



microspheres during mechanical ventricular assistance. Ann. Thorac. Surg. 11:43, 1971.

23. Rudolph, A. M., and Heymann, M. A. Methods for studying distribution of blood flow. Czrc. Res. 21:163, 1967.

24. Rudolph, A. M., and Heymann, M. A. Measurement of flow in perfused organs using microsphere method. Acta Endocrinol. (Kbh.) 153: 112, 1972.

25. Taber, R. E. 26. Taber, R. E., Morales, A. R., and Fine, G.

postoperative low-cardiac-output syndrome. Ann. Thorac. Surg. 4: 12, 1967. 27. Utley, J. In discussion of G. D. Buckberg et al. [8]. 28. Wagner, H. N., Jr., Rhodes, B. A., Sasaki, Y., and Ryan, J. P. Studies of the

circulation with radioactive microspheres. Invest. Radiol. 4:374, 1969. 29. Wakabayashi, A., Kubo, T., Gilman, P. K., Fuber, W. F., Mullin, P. Hirai,

J., and Connolly, J. E. Pulsatile pressure-regulated coronary perfusion during ventricular fibrillation. Surg. Forum 22: 121, 1971.

30. Wexler, M. J., Ginsburg, A. D., Latzina, A., Aster, R. A., and Slapak, M. Twenty-four hour renal preservation and perfusion utilizing platelet- rich plasma. Ann. Surg. 174:811, 1971.

I n discussion of R. E. Taber et al. [26]. Myocardial necrosis and the

Discussion DR. HASSAN NAJAFI (Chicago, Ill.): Since the presentation of our clinical

review before this Society some five years ago, we have continued two parallel investigations at Presbyterian-%. Luke's Hospital in Chicago, namely, an experimental investigation using dogs and calves and a prospective clinical investigation.

The results of clinical investigation in the past four years have confirmed our original conclusion that LVHN is indeed multifactorial in origin. Significant LVH and comprised coronary perfusion-as in aortic valve replacement, for instance-are the prerequisites for development of LVHN. We have failed to see this lesion in the absence of one of these two factors. Undoubtedly, other factors such as ventricular fibrillation also potentiate or predispose to the lesion.

T h e duration of insult is very important. If the patient dies shortly after operation, the lesion is somewhat obscure. But if the same patient or the same set of circumstances lead to the death of the patient about a day or two later, you will see an intense lesion, as discussed by Dr. Becker.

Prolonged hypotension has been important, as has the use of cardiotonic drugs, especially isoproterenol. Every one of our patients who died of LVHN had been on isoproterenol for a long period after bypass.

We also have seen LVHN with a beating heart. We have had six or seven such lesions in patients whose hearts were permitted to contract in normal sinus rhythm and who unfortunately suffered the lesion.

I would like to endorse the recommendation of Dr. Becker and his group that we avoid fibrillation, especially when dealing with hypertrophied myocardium. We have to perfuse the coronary arteries selectively when we do an aortic valve replacement.

DR. NOEL H. FISHMAN (San Francisco, Calif.): I wish to criticize this presentation for two reasons. First, the description of the methods failed to indicate how ventricular fibrillation was maintained at normothermic tempera- tures. Presumably clarification will be forthcoming in the published paper. For the time being, however, I must assume that ventricular fibrillation was maintained for the duration of the perfusion by continuous application of electric current, a technique which itself may adversely alter the distribution of coronary blood flow within the myocardium.

Second, by comparing the subendocardial necrotic lesions they produced with those found in isolated instances after cardiac procedures in several different



institutions, the authors implied that the mechanism of myocardial damage was the same in both the clinical and the experimental setting. This is an intriguing suggestion, but it assumes that the clinical setting was reproduced in the design of these experiments. I doubt that this was the case, since no mention was made in the presentation of the effects of such commonly employed clinical modalities as hypothermia, ischemic arrest, and hemodilution.

PRESIDENT BENSON B. ROE: I have one additional question for Dr. Becker. Was the induced electrical fibrillation maintained throughout the experiment, or was the fibrillation induced electrically and then turned off? That is, was the electric current sustained throughout the period of fibrillation?

DR. BECKER: Dr. Roe and Dr. Fishman, these hearts all fibrillated spontaneously immediately upon the institution of cardiopulmonary bypass, so no electrical fibrillation was needed nor was it necessary to maintain an electric current during the course of bypass.

In response to Dr. Fishman’s criticism, it would require an extremely large experimental series to reproduce all the possible clinical situations in which LVHN might be seen. Therefore we did not attempt to reproduce any of the clinical situations exactly; we only tried to duplicate the situation of cardiopulmonary bypass itself.

I should mention that none of these hearts were decompressed during the period of cardiopulmonary bypass. The pericardium remained intact over the entire heart except for the portion of right atrium that had to be exposed for cannulation. Because of this we decided that venting was not necessary.

I would like to thank Dr. Najafi for his remarks. I think we would agree with everything he has said, and we are certainly indebted to him for his experimental and clinical studies on the nature of LVHN.

In closing, I would like to emphasize that despite what we have learned from this experiment and those of others, we expect to continue to see LVHN. We plan to continue our efforts to define further the pathogenesis of the lesion, and we would like to encourage surgeons in other centers to get interested in this lesion and to encourage their pathology associates to look for it. We are quite sure that LVHN contributes to morbidity and mortality after bypass in every center using cardiopulmonary bypass.


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Distribution of Coronary Blood Flow During Cardiopulmonary Bypass in Pigs