Cardiovascular actions after intravenous and intracoronary administration of the slow channel blocker bepridil.

The effects of 1-[3-isobutoxy-2-(benzylphenyl)amino]propyl pyrrolidine hydrochloride (bepridil), a new calcium channel blocker, on the systemic and coronary circulation were studied in intact anesthetized domestic pigs. Intravenous administration (0.125-0.500 mg X kg-1 X min-1 over 5 min) caused dose-dependent decreases in systemic (8-26%) and coronary vascular resistance (10-41%), but had only a minor effect on cardiac output and myocardial contractility. Myocardial O2-consumption decreased slightly (1-15%). After administration of 0.5 mg X kg-1 X min-1 there was a slight decrease in heart rate. Intracoronary (i.c.) administration (500-1500 micrograms) had only a slight effect on global hemodynamics and regional myocardial wall function but caused large increases in coronary blood flow (100%) and coronary venous O2-content (140-170%), while myocardial O2-consumption decreased by 40-60%. This decrease in O2-consumption after bepridil i.c. in the absence of significant hemodynamic changes is discussed in terms of a more efficient O2-energy metabolism. The severe hypotension after intravenous administration will enhance catecholamine release and may mask this beneficial effect of bepridil on myocardial O2-consumption during the latter mode of administration.