L-cis Diltiazem attenuates intracellular Ca²⁺ overload by metabolic inhibition in guinea pig myocytes

We have previously demonstrated that treatment with L-cis diltiazem reduced cardiac infarct size in vivo. To examine the effect of L-cis diltiazem on Ca²⁺ overload induced by ischemia/reperfusion, we used a model for Ca²⁺ overload produced by metabolic inhibition in isolated guinea pig myocytes. Intracellular Ca²⁺ concentration ([Ca²⁺](i)) was quantified by fura-2 fluorescence microscopy and Ca²⁺ overload was induced by inclusion of 1 μM of carbonyl cyanide m-chrolophenylhydrazone (CCCP) for 40 min treatment followed by washout for 30 min. This treatment caused a large [Ca²⁺](i) elevation as well as a sustained contracture of the cardiomyocytes. The increase was suppressed by 10 μM of 2-[2-[4-(4-nitrobenzyloxy) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), a specific inhibitor of the Na⁺/Ca²⁺ exchanger, but not by nitrendipine (10 μM). L-cis Diltiazem (10 μM) attenuated the [Ca²⁺](i) increase, suggesting that L-cis diltiazem elicits a cardioprotective effect via attenuation of the [Ca²⁺](i) increase induced by metabolic inhibition and energy repletion. Copyright (C) 1999 Elsevier Science B.V.