J Thorac Cardiovasc Surg 1994;108:1153-1154
© 1994 Mosby, Inc.
Use of hyperpolarizing agents for induction of cardiac arrest during cardioplegia
Neri M. Cohen, MD, PhD,
Ralph J. Damiano,, Jr., MD,
Andrew S. Wechsler, MD
Division of Cardiothoracic Surgery
Department of Surgery, Box 68
Medical College of Virginia
Virginia Commonwealth University
Richmond, VA 23298-0068
Reply to the Editor:
Important species-dependent differences in the electrophysiologic properties of ion channels have been identified and characterized from many tissues
1-4 Clear differences exist in the calcium currents from nerve, skeletal muscle, smooth muscle, and heart muscle, as well as from many other cells types. 5 Furthermore, the relative contributions of various potassium currents to repolarization are clearly species-dependent. 3 Important differences include the magnitude of the current, the voltage-dependence of the inactivation rate constants, the type(s) of channels involved in the action potential, the voltage-dependence of the activation and of the inactivation processes, and the pharmacology of the currents. 6 Thus, if one is interested in describing properties of human heart cells, one cannot always extrapolate from the animal model to the clinical situation. However, animal models are useful and necessary to test hypotheses and refine new ideas. We agree that more work in clinically relevant models is needed to test the utility of this novel myocardial protection strategy. Toward this end, we have tested the efficacy of hyperpolarized arrest myocardial protection in the intact animal. Modifications of standard state-of-the-art clinical electrophysiologic techniques were used to measure the effects of surgical ischemia and hyperpolarizing cardioplegic myocardial protection during cardiopulmonary bypass on myocardial tissue. The porcine model was used because of the similarity of the species' coronary circulation and specialized conduction system to that of the human being. Preliminary data support the contention that hyperpolarized arrest myocardial protection is feasible, and further work in large animal models of cardiopulmonary bypass and global surgical ischemia is ongoing.
The profibrillatory effects of hyperpolarizing agents, for example, adenosine or adenosine triphosphate–dependent potassium channel opening agents, are well established and are accepted as a problem with hyperpolarized arrest. It is not clear, however, whether reperfusion-induced ventricular fibrillation in a surgical setting (e.g., after depolarized arrest) is important clinically. 7-9 Thus it will be important to study the role of this particular ventricular fibrillation, in the controlled setting of surgical ischemia, on myocardial performance.
References
-
Coraboeuf E, Vassort G. Effects of some inhibitors of ionic permeabilities on ventricular action potential and contraction of rat and guinea-pig hearts. J Electrocardiol 1968;1:19-30.[Medline]
-
Trautwein W, Pelzer D. Voltage-dependent gating of single calcium channels in the cardiac cell membrane and its modulation by drugs. In: Marme D, ed. Calcium and cell physiology. Berlin: Springer-Verlag, 1985:54-93.
-
Hume JR, Uehara A. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes. J Physiol (Lond) 1985;368:525-44.[Abstract/Free Full Text]
-
Pelzer D, Pelzer S, McDonald TF. Calcium channels in heart. In: Fozzard HA, Haber E, Jennings RB, et al. The heart and cardiovascular system. New York: Raven Press. 1992:1049-89.
-
Eckert R, Chad JE. Inactivation of Ca channels. Prog Biophysi Mol Biol 1984;44:215-67.
-
Cohen NM, Lederer WJ. Calcium current in single human cardiac myocytes. J Cardiovasc Electrophysiol 1993;4:422-37.[Medline]
-
Holman WL, Spruell D, Pacifico AD. Duration of asystolic reperfusion and reperfusate electrolyte composition influence postcardioplegia ventricular fibrillation. J THORAC CARDIOVASC SURG 1993;106:511-9.[Abstract]
-
Kinishita K, Mitani A, Tsuruhara Y, Kanegae Y, Tokunaga K. Analysis of determinants of ventricular fibrillation induced by reperfusion: dissociation between electrical instability and myocardial damage. Ann Thorac Surg 1992;53:999-1005.[Abstract]
-
Bolli R, Myers ML, Zhu WX, Roberts R. Disparity of reperfusion arrhythmias after reversible myocardial ischemia in open chest and conscious dogs. J Am Coll Cardiol 1986;7:1047-56.[Abstract]
