Myocardial perfusion distal to an acute or chronic coronary artery occlusion: effects of diltiazem and nifedipine

Abstract

The effect of two slow channel calcium antagonists, diltiazem and nifedipine, on perfusion of normal and ischemic myocardium was studied in anesthetized dogs with acute or chronic (ameroid constrictor) left anterior descending coronary artery occlusion. Diltiazem (15 and 30 micrograms/mkg/min i.v.) produced significant (P less than .05) and dose-related decreases in heart rate and mean aortic blood pressure and an increase in left circumflex coronary blood flow. Nifedipine (1 and 3 micrograms/kg/min i.v.) also produced a significant reduction in mean aortic blood pressure and an increase in left circumflex coronary artery blood flow; however, no change in heart rate was observed. Both diltiazem and nifedipine increased myocardial blood flow in the normal zone in dogs with acute or chronic coronary artery occlusion, and this effect was potentiated when aortic blood pressure was prevented from decreasing. Following a reduction in aortic blood pressure no significant change in ischemic zone perfusion was observed after diltiazem in dogs with an acute occlusion; flow was significantly increased in dogs with a chronic occlusion. In both models, diltiazem produced a redistribution of ischemic zone blood flow to the subendocardium. In dogs with acute or chronic occlusion nifedipine produce an increase in ischemic zone flow primarily to the subepicardium. The effect of each agent on tissue perfusion was enhanced in the chronic occlusion model. These data demonstrate marked differences in effects of diltiazem and nifedipine on hemodynamics and regional myocardial perfusion and stress the importance of experimental models in evaluating the effects of the calcium antagonists on coronary collateral blood flow.