Anoxic Injury during Cross-Clamping

CORRESPONDENCE

Anoxic Injury during Cross-Clamping To the Editor: In a recent article in The Annals (Ann Thorac Surg 29:217, 1980), Engelman and colleagues made the conclusion that the summation of anoxic injury occurring with intermittent aortic cross-clamping was greater than that with continuous aortic crossclamping during cardiac anoxia and cardiopulmonary bypass utilizing potassium chloride cardioplegia because of the allegedly greater reperfusion edema occurring with multiple reperfusions. This conclusion was based on the observation that an experimental group of 7 pigs in which the aorta was continuously cross-clamped and hypothermic potassium cardioplegia was employed had better left ventricular contractility and compliance studies after anoxic arrest than another group of 7 pigs with intermittent normothermic reperfusion and hypothermic cardioplegia. The authors' opinion concerning left ventricular contractility and compliance was made on the observation that the continuously cross-clamped group had postarrest maintenance of 51 f 129'0 (standard error of the mean) of prearrest contractility measurements and postarrest mainte31% of prearrest compliance meanance of 34 surements while no measurements could be made in the other group. This observation, of course, is without statistical significance. Also, the large variance (+ 31% being as large as the continuous postarrest group mean compliance) suggests that a large number of animals in the continuous group had unmeasurable postarrest function studies likewise. The profound implication that one should allow anoxic hearts to remain substrate deprived for prolonged periods is unwarranted, based on such scanty statistical backing. Such statistical nakedness is further reinforced in that the authors provided information demonstrating that the intermittently cross-clamped group was not statistically similar to the continuously cross-clamped group but, in fact, was in a poorer cardiac status before anoxic arrest. The intermittently cross-clamped group only had 4.75 k 0.5 pmoles of creatinine phosphate in the control prearrest period compared with the continuously cross-clamped group, which had nearly double the amount of this high-energy phosphate at 7.23 k 0.46 pmoles. This was significantly greater at p < 0.005. The only conclusion one could reach is that the intermittent group was relatively substrate deprived before anoxic arrest, and this again reflects a poorer group of experimental animals that may have been more stressed prior to the performance of the experiment. With this inconsistency concerning substrate levels in a possibly worse group of hearts, the lack of comparative prearrest functional information in the paper detracts from any conclusion that could be made about the functional state after arrest. There-

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fore, one must reach the verdict that the conclusion-intermittent cross-clamping per se, all other things equal, results in greater damage than continuous cross-clamping-cannot be made in this paper. Clinical evidence in a recent large series of patients points in the other direction [l].

David M . Lolley, M . D . Trover Clinic Clinic Drive Madisonville, KY 42431

Reference 1. Lolley DM, Ray JF 111, Myers WO, et al: Is reperfusion injury from multiple aortic cross-clamping a current myth of cardiac surgery? Ann Thorac Surg 30:llO. 1980

Reply To the Editor: Dr. Lolley's critique of a well-controlled study unfortunately detracts from the conclusions to be gained from the work. Further, the out-of-context reporting of data that require interpretation serves to present erroneous conclusions. First, in comparing groups of animals, 7 is a sufficient number from which to draw valid conclusions. Myocardial contractility and compliance were analyzed according to the methods described in the manuscript. The fact that contractility decreased to 51 k 12% of control following continuous arrest and was not measurable in 6 of 7 animals following intermittent arrest because of an absence of contractile force is not without statistical significance. There is nothing more significant than a nonbeating heart. Furthermore, the inference that myocardial compliance, which was 34 f 31% of control in the continuous arrest group, is an invalid measurement because of a large variance shows a lack of understanding of the technique used to quantitate myocardial compliance. The method used compares each animal's postarrest left ventricular end-diastolic pressure (LVEDP) to the prearrest level at the same ventricular volume and then takes a percentage. Thus, animals may actually have a large negative compliance change (e.g., if the LVEDP is considerably greater postarrest than prearrest) or a zero change or even an increased compliance relative to control. In this experiment, the change in compliance averaged -66 f 31% of control, which means compliance was 34 k 31% of the prearrest or control compliance. The variance or SEM does not invalidate this result. Second, myocardial high-energy phosphate data as presented in the paper incorporate different animals than were used for the contractility studies. It is recognized that prearrest or control creatine phosphate

395 Correspondence

during cardiopulmonary bypass. Surgery 80:266, (CP) levels are considerably different in the two 1976 groups reported while adenosine triphosphate (ATP) levels are essentially identical. No ready explanation 4. Engelman RM, Rousou JH, Auvil J: The safety of prolonged ischemic arrest using hypothermic carfor this discrepancy is available other than the most dioplegia. J Thorac Cardiovasc Surg 79:705, 1980 plausible one-that the two groups were not studied within the same time frame and reagent differences may have existed in the CP testing. The explanation Neomycin Ototoxicity given by Dr. Lolley of substrate deprivation in the To the Editor: low CP group does not hold up because All' control I was greatly interested in the report by Jonathan measurements in these same intermittent arrest ani- Meakins and Jean Allard entitled "Neomycin Abmals were essentially identical to those in the con- sorption following Clagett Procedure for Postpneutinuous arrest group. In order not to compare apples monectomy Empyema" (Ann Thorac Surg 29:32, with oranges, each group of animals was compared 1980). I am afraid, however, that the authors did with itself. As noted, in the continuous arrest group, not do their homework thoroughly enough with ATP fell 25% from control with reperfusion while CP specific reference to neomycin ototoxicity from refell 20% and with intermittent arrest, ATP fell 37% peated intrapleural irrigations. while CP fell 17%. No attempt was made to imply In 1971, I [6] wrote on empyema and alluded to 6 these changes were significant, which they obvi- personal patients who underwent successful closure ously are not, but the general trend with intermittent of postpneumonectomy empyema as originally dearrest (obvious in Figure 3 and 4) is for a declining scribed by Clagett and Geraci [l]; neomycin solution postreperfusion ATP and CP level with each succes- 0.25% was instilled only once at closure. In the same sive arrest, a sign of worsening metabolic reserve article, I discussed briefly the reports by Myerson with repeated reperfusion. and co-workers 151, Helm 121, Leach 131, and Melon Finally, and most important, what clinical impli- (41, each of whom described separate instances of secations accrue from this work? I believe one is that vere ototoxicity following repeated irrigations of neointermittent arrest with "inadequate" reperfusion is mycin. a poor preservation technique. This paper [l]and Over the intervening years, my associates and I others 12, 31 we have published previously would have had a 90% rate of success with approximately 15 support this. Indeed, in coronary revascularization postpneumonectomy empyemas closed after the procedures, we have been unable to correlate the du- manner of Clagett. There have been no instances of ration of cardioplegic arrest (even up to three hours) ototoxicity or renal toxicity. Because of the frequency with myocardial injury [4]. However, when massive of Staphylococcus aureus and pseudomonas infechypertrophy is present, as when multiple valves tions, we usually pack the opened cavity with gauze need replacing and revascularization is to be per- impregnated with citric acid. At closure, bacitracin formed, interrupting the arrest interval would seem and Coly-Mycin (colistin sulfate) are added to the prudent. However, the duration of intermittent re- 0.25% neomycin solution. perfusion should be appropriate to replace metaboIn 1972, Stafford and Clagett [7] reported their total lites and allow recovery of metabolic processes. How experience with 18 patients; ototoxic reactions devellong this should be and how best to accomplish it oped in none. Neomycin was used as an irrigant in remains a matter of investigation. only 1patient after open drainage, and shortly thereafter an itchy rash developed. The administration of Richard M . Engelman, M . D . neomycin was stopped promptly. Chief, Cardiac Surgery Meakins and Allard are entirely correct in stating Baystate Medical Center that no postoperative serum levels of neomycin have 759 Chestnut S t been previously.recorded. They have shown that, in Springfield, M A 01 107 general, serum levels less than 10 yg per milliliter do not cause toxic reactions. References I am not quite sure why Clagett and Geraci [l] de1. Engelman RM, Rousou JH, O'Donoghue MJ, et al: cided to use 0.25% neomycin for a one-time instillaA comparison of intermittent and continuous ar- tion. Perhaps it was a bit of serendipity, although rest for prolonged hypothermic cardioplegia. Ann they were well aware of the potentials of neomycin Thorac Surg 29:3, 1980 toxicity. In the article under discussion, perhaps it 2. Engelman RM, Adler A, Gouge TH, et al: The ef- was lucky that the authors were able to obtain negafect of normothermic anoxic arrest and ventricular tive cultures so quickly while irrigating with 1% fibrillation on the coronary blood flow distribu- neomycin solution. tion of the pig. J Thorac Cardiovasc Surg 692358, Paul C . Samson, M . D . 1975 3. Engelman RM, Chandra R, Baumann FG, et al: 3300 Webster St Myocardial reperfusion, a cause of ischemic injury Oakland, C A 94609