EFFECTS OF OPC-18790, A NEW POSITIVE INOTROPIC AGENT, ON CANINE VENTRICULAR ARRHYTHMIAS

OPC-18790 is a positive inotropic and vasodilating agent that increase s intracellular cyclic AMP and stimulates Ca currents. We examined its direct electrophysiological effects in isolated blood-perfused canine cardiac preparations. OPC-18790 caused an acceleration of the intrave ntricular conduction in association with an increase of the contractil e force and the coronary blood flow. We also examined the effects of O PC-18790 on ventricular arrhythmias in canine ventricular tachycardia (VT) models. OPC-18790 in doses producing submaximal inotropic effects , 3 mg/kg, i.v., increased the total heart rate, atrial rate and decre ased the blood pressure, but did not suppress or aggravate 24- and 48- hr coronary ligation VTs. OPC-18790 up to 3 mg/kg, i.v. also did not s uppress or aggravate digitalis-induced VTs. However, this dose of OPC- 18790 aggravated halothane-adrenaline induced VT into ventricular fibr illation and eventually death, but a lower dose of 0.3 mg/kg did not a ggravate this VT. These results in canine VTs indicate that OPC-18790 is similar to other positive inotropic agents, vesnarinone, amrinone, milrinone and sulmazole. The absence of an aggravating effect of this new positive inotropic agent on digitalis and coronary ligation VTs ma y be advantageous in a clinical setting of combined therapy with digit alis for myocardial ischemia.