Simvastatin‐sodium delays cell death of anoxic cardiomyocytes by inhibition of the Na+/Ca2+ exchanger

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Abstract
When incubated under anoxic conditions, cultured neonatal cardiomyocytes undergo cell necrosis. Simvastatin‐sodium, the bioactive metabolite of simvastatin (a potent serum cholesterol‐lowering drug), delayed the anoxia‐induced myocyte necrosis in a dose‐dependent manner. This beneficial effect of simvastatin‐sodium could not be attributed to its cholesterol‐lowering properties. We found that simvastatin‐sodium, at concentrations of 20 and 50 μM, attenuated the rise in intracellular Ca2+ concentration ([Ca2+]i) measured with Fura‐2 in anoxic cardiomyocytes. In a test of sarcolemmal Na+/Ca2+ exchange activity, simvastatin‐sodium attenuated the rise of[Ca2+]i upon incubation in sodium‐free buffer, which normally causes a reversal of Na+/Ca2+ exchange and cellular calcium overload. The inhibitory action of simvastatin‐sodium on the sarcolemmal Na+/Ca2+ exchanger could well explain the cardioprotective effect of the drug on myocytes subjected to anoxia.