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J Thorac Cardiovasc Surg 1997;114:515-516
© 1997 Mosby, Inc.

LETTERS TO THE EDITOR

Hypothermia during preconditioned ischemia-reperfusion attenuates the myocardial protection of preconditioning

Hôpital Lariboisière
2 rue Ambroise Paré
75010 Paris, France

Reply to the Editor:

We would like to thank Drs. Lu, Ying, and Guo for their kind remarks about our paper and share their enthusiasm for the study of the untapped endogenous cardioprotective mechanisms. We read with interest their report concerning the lesser efficacy of hypothermic preconditioning in the rat heart. Results presented in the study seem to show a lesser benefit of preconditioning when induced at a temperature of 31° C followed by 3 hours of cardiac arrest with hypothermic (4° C) crystalloid cardioplegic solution and 45 minutes of normothermic reperfusion. However, no control group data are presented for either the hypothermic or normothermic preconditioning experiments. Even though there does not appear to be any benefit from hypothermic preconditioning on the various hemodynamic parameters measured at the end of reperfusion compared with the ones reported immediately after preconditioning, there are no data to document what would have occurred if preconditioning had not been performed in the hypothermic setting. Perhaps omitting preconditioning in this situation would have caused greater deterioration of the contractility indices after reperfusion. We believe that in the experimental protocol presented, the difference in preconditioning effect should be compared with the appropriate control groups, which are hypothermic and normothermic nonpreconditioned animals, and the results presented as a function of these controls. Baseline hemodynamic data recorded before the preconditioning stimulus would also be helpful because the baseline parameters may indeed be already altered by hypothermia, which is known to affect numerous enzymatic pathways. Also, since the second time point of study is after 45 minutes of normothermic reperfusion, the recovery may be only delayed in the hypothermic group compared with the normothermic one and measurements at a later time point may be warranted. It is noteworthy that recent studies from the first group to report a metabolic benefit of preconditioning in clinical cardiac surgery, performed in the setting of normothermic ventricular fibrillation, failed to show any benefit when the preconditioning was induced at lower temperatures. ^{1, 2} Ischemic preconditioning may be an interesting adjunct to myocardial protection when cardioprotection is suboptimal, such as in long crossclamp times and inadequate delivery of cardioplegic solution, situations in which the heart is submitted to ischemic arrest rather than aerobic arrest. ³ Ischemic preconditioning has been found to confer equal but no additive benefit to hypothermia outside the two situations mentioned above. ⁴

In our study, although no rigid predictors of preconditioning ischemia, referred to in the letter, were used, we did see occasional electrocardiographic changes during induction of ischemia, and creatine kinase MB values and lactate gradients at the end of the preconditioning protocol suggested a greater ischemic insult in the preconditioned group, making us believe that a sufficient ischemic stimulus had indeed been delivered. Our data lead us to conclude that the benefits conferred by ischemic preconditioning before continuous normothermic blood cardioplegia, which results in aerobic cardioplegic arrest in most cases, are minimal and perhaps even detrimental, as reported by others. ⁵

Otherwise, we agree with the comments that numerous confounding factors may skew the preconditioning effect and should be controlled for in both experimental and clinical studies. These include the use of opioid agonists, volatile anesthetics, ⁶ -adrenergic agonists, aprotinin, and cardiopulmonary bypass itself, which all may have preconditioning effects. ⁷

Again we thank Lu, Ying, and Guo for their comments and the points they raise in the study of the endogenous cardioprotective mechanisms of the heart, which beg to be exploited in clinical cardiac surgery.

12/8/83073

References

1. Di Salvo C, Hemming A, Jenkins D, Yellon D, Oakley RE, Wright J, et al. Can the human myocardium be preconditioned with ischaemia under hypothermic conditions? Proceedings of the ninth annual meeting of the European Association for Cardiothoracic Surgery [abstract]; 1995 Sept 25-27; Paris. 1995. p. 324.
   
2. Jenkins DP, Pugsley WB, Yellon DM. Ischemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass grafts. Circulation 1996;94(Suppl):I170.
   
3. Galinanes M, Argano V, Hearse DJ. Can ischemic preconditioning ensure optimal myocardial protection when delivery of cardioplegia is impaired? Circulation 1995;92(Suppl):II389-94.
   
4. Cleveland JC Jr, Meldrum DR, Rowland RT, Banerjee A, Harken AH. Preconditioning and hypothermic cardioplegia protect human heart equally against ischemia. Ann Thorac Surg 1997;63:147-52. [Abstract/Free Full Text]
   
5. Kaukoranta P, Lepojarvi M, Ylitalo K, Kiviluoma K, Peuhkurinen K. Protection of the myocardium during normothermic retrograde blood cardioplegia with or without preceding ischaemic preconditioning [abstract]. Eur Heart J 1996;17(Suppl):108.
   
6. Novalijas E, Heisner JS, Fujita S. Stowe DF. Sevoflurane and preconditioning alter flow and nitric oxide release in isolated hearts [abstract]. FASEB J 1997;11:A246.
   
7. Perrault LP, Menasché P. Preconditioning during cardiac surgery. In: Marber MS, Yellon DM, editors. Ischaemia: preconditioning and adaptation. Oxford: BIOS Scientific Publishers; 1996. p. 187-206.
   

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Louis P. Perrault Philippe Menasché Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Perrault, L. P. Articles by Menasché, P. Search for Related Content PubMed Articles by Perrault, L. P. Articles by Menasché, P.