Electro-mechanical effects of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212), a new positive inotropic agent. Isolated adult canine Purkinje strands and ventricular trabeculae

Abstract

The electrical and mechanical effects of 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212), a new, non-glycosidic, positive inotropic agent, were examined in isolated adult canine purkinje strands and ventricular trabeculae. In isolated adult canine ventricular trabecular muscle, compound OPC -8212 increased force development in a concentration-dependent manner. OPC -8212 produced a concurrent increase in trabecular muscle transmembrane action potential durations measured at both 50% and 90% of repolarization. In isolated adult canine Purkinje strand preparations, compound OPC -8212 did not exhibit a positive inotropic effect. Compound OPC -8212 did, however, produce a concentration-dependent increase in Purkinje fiber transmembrane action potential durations that was proportionally greater than that observed in the trabecular muscle preparations. The effects of OPC -8212 on adult canine isolated Purkinje fiber and ventricular muscle electrical and mechanical characteristics are unlike those that have been reported for other drugs that increase myocardial inotropy; i.e. cardiac glycosides, catecholamines, amrinone, or phosphodiesterase inhibitors.