Effect of the calcium antagonist verapamil on necrosis following temporary coronary artery occlusion in dogs

Abstract

Calcium metabolism may play an important role in the pathogenesis of myocardial ischemic injury. The effect of the sarcolemmal calcium flux inhibitor, verapamil, on myocardial necrosis was studied in dogs subjected to temporary coronary artery occlusion. One group of dogs was untreated. A second group was given 0.8 mg/kg verapamil intravenously over a 30 min period beginning 10 min prior to coronary occlusion. In a third group, the dose of verapamil was increased until complicated by hypotension or conduction abnormalities. Cardiac necrosis was produced in all dogs by 40 min of left circumflex coronary artery occlusion followed by 2--4 days of reperfusion. At the end of the experiment, animals were sacrificed and necrosis was quantitated histologically in transmural slices through the posterior papillary muscle. Pre-treatment with the lower dose of verapamil resulted in significantly less necrosis (14% treated vs 35% untreated) with minimal hemodynamic consequences. Higher does of verapamil were even more effective in limiting cardiac necrosis despite the development of hypotension and varying degrees of heart block.