The effect of extracellular calcium concentration and Ca-antagonist drugs on enzyme release and lactate production by anoxic heart cell cultures

Abstract

Tissue cultures of neonate rat heart cells were subjected to anoxia for 16 h in the presence of 5 m m glucose and increasing concentrations of calcium in the incubation medium. When the calcium content of the culture medium was increased, release of intracellular enzyme was observed. Increased extracellular calcium concentration appeared to have no effect on normoxic tissue preparations. The time course of this anoxia-related change was examined. Increasing the calcium concentration of the medium caused an acceleration of the anoxia-induced rate of enzyme leakage when compared with anoxic cultures exposed to a low medium calicum concentration. The calcium-induced increase in anoxic enzyme release could be partially reversed by various concentrations of the calcium antagonist drugs verapamil and nifedipine. Verapamil and nifedipine both appear to reduce the extent to which an elevated medium calcium concentration is able to reduce myocyte ATP content under anoxic conditions. These drugs appear to be without effect on ATP content of anoxic cells exposed to a low calcium concentration on the medium. Calcium-induced increases in enzyme leakage cannot be modified by the provision of high medium glucose concentrations, and hypertonic solutions of mannitol exacerbate damage to myocytes under anoxic and hypercalcaemic conditions. These data suggest that high extracellular concentrations of calcium exacerbate damage to heart cells subjected to anoxia although the mechanism underlying this exacerbation is uncertain.