SIMVASTATIN-SODIUM DELAYS CELL-DEATH OF ANOXIC CARDIOMYOCYTES BY INHIBITION OF THE NA+ CA2+ EXCHANGER/

When incubated under anoxic conditions, cultured neonatal cardiomyocyt es undergo cell necrosis. Simvastatin-sodium, the bioactive metabolite of simvastatin (a potent serum cholesterol-lowering drug), delayed th e anoxia-induced myocyte necrosis in a dose-dependent manner. This ben eficial effect of simvastatin-sodium could not be attributed to its ch olesterol-lowering properties. We found that simvastatin-sodium, at co ncentrations of 20 and 50 mu M, attenuated the rise in intracellular C a2+ concentration ([Ca2+](i)) measured with Fura-2 in anoxic cardiomyo cytes. In a test of sarcolemmal Na+/Ca2+ exchange activity, simvastati n-sodium attenuated the rise of[Ca2+](i) upon incubation in sodium-fre e buffer, which normally causes a reversal of Na+/Ca2+ exchange and ce llular calcium overload. The inhibitory action of simvastatin-sodium o n the sarcolemmal Na+/Ca2+ exchanger could well explain the cardioprot ective effect of the drug on myocytes subjected to anoxia.