J Thorac Cardiovasc Surg 1994;108:1152-1153
© 1994 Mosby, Inc.
Use of hyperpolarizing agents for induction of cardiac arrest during cardioplegia
D. H. Boehm, MD
Department of Cardiac Surgery
University of Munich
Klinikum Grosshadern
Marchioninistr. 15
81377 Munich, Germany
To the Editor:
The article by Cohen and colleagues
1 regarding the use ofaprikalim, an adenosine triphosphate–sensitive potassium channel opener, for induction of cardioplegia provides interesting insights It is undoubted that hyperpolarized cardiac arrest is better than depolarized arrest with regard to energy-consuming processes like deactivation of calcium and sodium pumps. However a general defect of hyperpolarizing agents like analogs of chromakalin (adenosine triphosphate–sensitive potassium channel openers) may be their inability to limit ventricular fibrillation, whereas depolarization achieves this aim. 2 We 3 have shown that adenosine, which also acts as a hyperpolarizing agent added to Krebs-Henseleit buffer, failed to arrest hearts in an in vivo baboon model. After a short period of electromechanical quiescensce, a few seconds after the start of the infusion the hearts continued to fibrillate for about 55 seconds. This is in contradistinction to findings in the isolated rat heart by Schubert and associates, 4 who found a shortened period for induction of cardiac arrest with no period of ventricular fibrillation when adenosine was added to Krebs-Henseleit buffer. This indicates that there might be species-related differences with regard to ventricular fibrillation threshold. Bretschneider 5 indicated that the hearts of small animals have considerably different electrophysiologic properties that might be phylogenetically related to the much higher heart rate. This includes a considerably shorter plateau of the action potential, a different relationship of the fast sodium channels to the slow calcium and sodium channels of the external membrane, and probably a quantitatively different source of calcium-producing electromechanical coupling. 6 Therefore, before extrapolating from the results found in this isolated rabbit heart preparation of global surgical ischemia, further work is required to test the efficacy of potassium channel openers on other species closer related to man.
Further shortcomings of aprikalim and related compounds are the proarrhythmic properties, which need to be adressed before clinical use in cardioplegic solutions.
References
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Cohen NM, Wise MW, Wechsler AS, Damiano RJ. Elective cardiac arrest with a hyperpolarizing adenosine triphosphate–sensitive potassium channel opener. A novel form of myocardial protection? J THORAC CARDIOVASC SURG 1993;106:317-28.[Abstract]
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Opie LH, de Jong JW, Owen P. New modes of cardioplegia [Abstract]. J Mol Cell Cardiol 1989;21(Suppl IV):4 (L21).
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Boehm DH, Human PA, von Oppell U, et al. Adeno sine cardioplegia: Reducing reperfusion injury of the ischaemic myocardium? Eur J Cardiothorac Surg 1991;5:542-5.[Abstract]
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Schubert T, Vetter H, Owen P, Reichart B, Opie LH. Adenosine cardioplegia: adenosine versus potassium cardioplegia—effects on cardiac arrest and postischemic recovery in the isolated rat heart. J THORAC CARDIOVASC SURG 1989;98:1057-65.[Abstract]
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Bretschneider HJ. Myocardial protection. Thorac Cardiovasc Surg 1980;28:272-95.
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Fabiato A, Fabiato F. Calcium induced release of calcium from the sarcoplasmatic reticulum and skinned cells from adult human, dog, cat, rabbit, rat and frog hearts and from fetal and newborn rat ventricles. Ann N Y Acad Sci 1978;308:491-522.
