Effects of Intracoronary Bay k 8644, a Calcium Channel Agonist, in Anesthetized Dogs

Abstract

Bay k 8644, a new dihydropyridine calcium channel activator has been shown to have positive inotropic and vasoconstrictor properties following intravenous (i.v.) administration. In the present study, intracoronary administration of Bay k 8644 was used to isolate drug effects on regional myocardial blood flow and contractility independent of systemic hemodynamic actions in beta-adrenoceptor-blocked anesthetized dogs. Intracoronary infusion of Bay k 8644 (1.5, 3.7, 7.4, 14.8 micrograms/min) produced significant increases in contractility (percentage of segment shortening) in the drug-perfused region. Peak positive dP/dt, an index of global contractility, was increased in parallel with increases of regional contractility. No other changes in systemic hemodynamics occurred. Transmural tissue blood flow distribution as measured by radioactive microspheres was also unchanged by Bay k 8644. Intracoronary infusion of KB-944, a nondihydropyridine calcium channel blocking agent, increased coronary blood flow and decreased regional segment shortening and peak positive dP/dt. KB-944 inhibited increases in contractility produced by Bay k 8644. Thus, Bay k 8644 was shown to have a direct positive inotropic effect in vivo which was inhibited by calcium channel blockade.