Calcium antagonists and the acutely ischemic heart: experimental effects on ventricular fibrillation and enzyme...

To investigate and to compare the protective action of verapamil, nifedipine and diltiazem on the acutely infarcting myocardium, we studied effects on cellular damage and mechanical function in the isolated working rat heart preparation subjected to left main coronary artery ligation. First, the fall in the ventricular fibrillation threshold (VFT) was diminished by all three agents, but non-specific effects of these agents were operating at least in part. All three compounds afforded substantial dose-dependent reduction of lactate dehydrogenase release, which was taken as an index of cellular damage, and preserved ATP stores in the infarcting myocardium. The range of effective concentrations was small and close to doses which produced atrioventricular conduction disturbances (verapamil, diltiazem) or LV pump failure (nifedipine). It is argued that these concentrations may be therapeutically relevant, whereas the concentration of a beta-adrenoceptor antagonist agent required comparably to inhibit enzyme release was supra-therapeutic (metoprolol 10(-4) M). There are substantial differences between such animal models and the situation in acute myocardial infarction in man, where preliminary data show benefits both for beta-adrenergic blockade by sotalol and for calcium antagonism by nifedipine.