Mechanisms of the Beneficial Effects of Some Ca2+ Antagonists on the Ca2+-Paradox in Myocardium
Electrophysiological experiments have provided evidence that Ca2+ antagonists such as verapamil and diltiazem alter cardiac function by inhibiting the entry of Ca2+ through slow calcium channels (1–3). These agents therefore can be seen to protect myocardium under pathophysiological conditions which are associated with a massive amount of Ca2+ entry and the occurrence of intracellular Ca2+ overload. Reperfusion of an isolated rat heart with a medium containing Ca2+ after a brief period of perfusion with a Ca2+ -free medium has been shown to produce contractile abnormalities, myocardial cell damage, depletion of high energy phosphate stores, alterations in cation contents, enzyme leakage and changes in subcellular Ca2+ -transport (5–12). These Ca2+ -paradoxic effects have been attributed to the occurrence of intracellular Ca2+ -overload (8); however, the mechanisms of these changes in the myocardium are far from clear. Some investigators have shown the protective effects of both verapamil and diltiazem against the Ca2+ -paradox related myocardial injury and have interpreted their results to mean that the massive Ca2+ -influx during Ca2+ -paradox is occurring through the slow calcium channels (13–15). On the other and, concentrations of verapamil, which are known to block Ca2+ -currents, were reported to be ineffective in preventing the Ca2+ -paradoxic changes (16,17). Accordingly, it has been suggested that some other mechanism of Ca2+ influx or efflux such as Na –Ca2+ exchange may also be involved in eliciting Ca2+ -paradoxic effects on the myocardium (18,19). This study was therefore undertaken to examine the effects of both low and high concentrations of verapamil and diltiazem on some Ca2+ -paradox changes in the myocardium. Furthermore, the actions of these agents Na+ -Ca2+ exchange mevhanism in the sarcolemmal preparations were studied.
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- 19.Dhalla NS, Alto LE, Singal PK: Role of Na+ -Ca2+ exchange in the development of cardiac abnormalities due to calcium paradox. Europ Heart J: in press, 1983.Google Scholar