Warm Cardioplegia or Aerobic Cardioplegia? Lei'sCall a Spade a SpadePhilippe Menasche, MD, PhDDepartment of Cardiovascular Surgery, H6pital Lariboisiere, Paris, France

Since its introduction in clinical practice [1], warm bloodcardioplegia has generated a continuing number of

experimental and clinical studies that often have gener­ated conflicting data. As a result, many surgeons now arecompletely confused about this technique, and this obser­vation really is frustrating in view of the tremendousamounts of time, effort, and money that have beendevoted to studies supposed to clarify the respectiveadvantages and disadvantages of warm cardioplegia, ascompared with conventional hypothermia-based myocar­dial protection techniques. I think that most of the confu­sion arises from the fact that the design of several of thesestudies has failed to adhere strictly to the fundamentaltechnical principles that underlie the concept of aerobicarrest. This term actually should be preferred to that ofnormothermic arrest to emphasize that the primary endpoint is to avoid (as much as possible) ischemic (and,consequently, reperfusion) damage to the myocardiumduring the cross-clamp period, and not to stick firmly tostrict normothermia (which, in practice, is seldom main­tained because of the trend of most surgeons to allow fora drift of core temperature, usually in the range of 33°C).

It therefore may be appropriate to briefly state theprerequisites for myocardial metabolism to remain aerobic

See also page 41.

during the period of aortic occlusion. Failure to complywith these prerequisites does not imply that the techniqueunder investigation will yield poor protection. It simplyimplies that this technique is not a technique of aerobicarrest, even if it has been performed under almost nor­mothermic conditions.

By definition, maintenance of cardiac aerobic metabolicpatterns during arrest requires oxygen supply to matchoxygen demand. It should be realized that none of the rat,dog, pig, or other animal species studies ever will permitthe researcher to determine accurately, in a given patient,the exact amount of the residual metabolic requirementsof the arrested heart. This has resulted in the concept ofsupplying as much oxygen as possible to avoid an energyimbalance and the resulting shift of myocardial metabo­lism toward anaerobic patterns. Consequently, if oneassumes that oxygen demand has been, once and for all,drastically reduced by adequate induction and maintenanceof asystole, it results that the prerequisites for sustained

Address reprint requests to Dr Menasche, Department of CardiovascularSurgery, H6pital Lariboisiere, 2 rue Ambroise Pare, 75475 Paris Cedex la,France.

© 1994 by The Society of Thoracic Surgeons

aerobiosis primarily have to deal with the modalities ofoxygen supply [2]. These modalities can be summarizedas follows:

1. Oxygen must be present in sufficient quantities, andthere is now convincing evidence that hematocrit shouldbe at least equal to 24% [3]. I even try to keep it slightlyhigher.

2. Oxygen must be delivered at a sufficient flow rate.Although some uncertainties still persist with regard tothe "optimal" flow rates of cardioplegia delivery throughthe coronary sinus, there is a general agreement that anaverage of 150 mLimin probably represents the loweracceptable limit. The upper limit, which is largely deter­mined by the corresponding infusion pressure, is likely tobe around 200 mLimin, in particular in patients withhypertrophied hearts [4], keeping in mind that flow ratesin excess of 200 mLimin may not automatically conferadditional protection because they have been shown toincrease the shunting fraction of the retroperfusate at theexpense of its nutritive component [5].

3. Oxygen must be delivered in a continuous fashionbecause it is consumed overtime. No matter what the "safe"ischemic interval is in experimental models [6], it isvirtually impossible to predict, in a given patient, the timepoint beyond which myocardial metabolism is going toshift toward anaerobic patterns as well as the extent andreversibility of tissue damage that may occur beyond thiscut-off time mark. It is a matter of good sense thatoccasional discontinuation of cardioplegia administrationfor periods of, say, 2 to 3 minutes, is likely to be incon­sequential. Nevertheless, in the study by Pelletier andco-workers reported in this issue of TheAnnals [7], as wellas in others [8], the cumulative period of cardioplegia flowinterruption represented 30% to 50% of the total cross­clamp time. Although such an approach does not, appar­ently, preclude the achievement of good clinical results,intermittent normothermic blood cardioplegia is, in thissetting, a misnomer, and the technique should moreappropriately be referred to as intermittent normothermicischemic arrest. The finding, in another study [8], thatretrograde warm blood cardioplegia is associated withlactate production is not unexpected when cardioplegiadelivery has been turned off during 30% of the total aorticcross-clamp time, and one then should not be surprised tofind metabolic patterns of ischemia when ischemic condi­tions have been created intentionally. As to the hypothe­sis that repetitive periods of short ischemia could protectthe heart through some preconditioning effect, it is psy­chologically attractive in that surgeons may no longer feel

Ann Thorac Surg 1994;58:5--6 • 0003-4975/94/$7.00

6 EDITORIAL MENASCHEWARM OR AEROBIC CARDIOPLEGIA?

Ann Thorae Surg1994;58:5--6

"guilty" about shutting off cardioplegia delivery, but thereality of the preconditioning hypothesis in this specificsetting remains to be determined.

4. Oxygen must be delivered as uniformly as possiblethroughout the myocardium. When tight stenoses, andfurthermore, complete occlusions of the coronary arteriesare present, there is now a convincing body of evidencethat retrograde or combined (retrograde/antegrade) ap­proaches are more effective in ensuring homogeneousdistribution of cardioplegia than the antegrade route ofadministration alone [9, 10]. This may account for thefailure of Pelletier and co-workers [7] to have achievedasystole in 13 of their normothermic, antegradely per­fused patients. Support for this hypothesis comes fromthe observation that although cooling was effective ininducing asystole in 12 of these 13 crossover patients, theuse of the retrograde technique was, in 1 case, the onlymeans of achieving electromechanical arrest. One there­fore should realize that failure of ensuring consistentasystole throughout the cross-clamp period, a purporteddrawback of "warm" cardioplegia, may be related more tothe route of cardioplegia delivery than to the temperatureof the solution. From this standpoint, it needs to beemphasized that in coronary bypass operations, only theretrograde approach allows the surgeon to deal techni­cally with the egress of blood through coronary arteriot­omies and, as such, is an important component of the"continuous delivery" concept.

Thus, only the simultaneous combination of the above­mentioned factors (high hematocrit, high flow rate ofdelivery, continuous or almost continuous delivery, andretrograde or combined route of delivery) defines thetechnique of aerobic arrest. Multiple variants of thistechnique are possible, and indeed are commonly usedclinically, but they should be labeled as such. Given themethodologic difficulties inherent in clinical trials, a strin­gent definition of the warm aerobic cardioplegia tech­nique is mandatory if one wants its comparison withconventional hypothermia-based techniques to generatemeaningful data and therefore to clarify the following, yetunanswered question: Is warm aerobic arrest an intellec­tually attractive concept that is, however, not translated interms of improved postoperative patient outcome, or is it

a real breakthrough and, if so, in which patient sub­groups?

Although my 3-year clinical experience with warmcardioplegia has been satisfactory overall, I am not a blindzealot of this technique and strongly consider that itspitfalls and drawbacks should not be understated. How­ever, it is equally fair that judgments about "warm"cardioplegia really refer to a technique that addresses thefundamental principles of aerobic arrest, and not to vari­ants entitled "warm" only for the reason that bloodcardioplegia is not delivered as cold as it used to be. Onceagain, the important distinction to make is not betweenwarmand cold cardioplegia but rather between aerobic andischemic arrest.

References1. Lichtenstein SV, Ashe KA, El Dalati H, Cusimano RJ, Panos

A, Slutsky AS. Warm heart surgery. J Thorac CardiovascSurg 1991;101:269-74.

2. Menasche P, Peynet J, Touchot B, et al. Normothermiccardioplegia: is aortic cross-clamping still synonymous withmyocardial ischemia? Ann Thorac Surg 1992;54:472--8.

3. Yau TM, Weisel RD, Mickle DAG, et al. Optimal delivery ofblood cardioplegia. Circulation 1991;84(Suppl 3):38D-8.

4. Gundry SR, Wang N, Bannon D, et al. Retrograde continu­ous warm blood cardioplegia: maintenance of myocardialhomeostasis in humans. Ann Thorac Surg 1993;55:358--63.

5. Ikonomidis JS, Yau TM, Weisel RD, et al. Optimal flow ratesfor retrograde warm cardioplegia [Abstract]. Circulation1992;86(Suppl 1):102.

6. Ko W, Zelano J, Fahey AL, Berman K, Isom OW, Krieger KH.Ischemic tolerance of the arrested heart during warm cardio­plegia. Eur J Cardiothorac Surg 1993;7:295-9.

7. Pelletier LC, Carrier M, Leclerc Y, Cartier R, Wesolowska E,Solymoss Be. Intermittent antegrade warm versus coldblood cardioplegia: a prospective, randomized study. AnnThorac Surg 1994;58:41-9.

8. Yau TM, Ikonomidis JS, Weisel RD, et al. Which techniquesof cardioplegia prevent ischemia? Ann Thorac Surg 1993;56:102D-8.

9. Noyez L, van Son JAM, van der Werf T, et al. Retrogradeversus antegrade delivery of cardioplegic solution in myocar­dial revascularization. J Thorac Cardiovasc Surg 1993;105:854--63.

10. Misare BD, Krukenkamp IB, Lazer ZP, Levitsky S. Retro­grade is superior to antegrade continuous warm blood car­dioplegia for acute cardiac ischemia. Circulation 1992;86(SuppI2):393--7.