Effects of OPC-18790, a New Positive Inotropic Agent, on Canine Ventricular Arrhythmias

Abstract

ABSTRACT-OPC-18790is a positive inotropic and vasodilating agent that increases intracellular cyclic AMP and stimulates Ca currents. We examined its direct electrophysiological effects in isolated blood-per fused canine cardiac preparations. OPC-18790 caused an acceleration of the intraventricular conduction in association with an increase of the contractile force and the coronary blood flow. We also examined the effects of OPC-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 decreased 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 suppress or aggravate digitalis-induced VTs. However, this dose of OPC-18790 aggravated halothane-adrenaline induced VT into ventricular fibrillation and eventually death, but a lower dose of 0.3 mg/kg did not aggravate 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 may be advantageous in a clinical setting of combined therapy with digitalis for myocardial ischemia.

Evaluation of Inotropic Activity of Fluorobenzene Derivative Using an Isolated Rat Heart Model

“…All these data have led to the search for new therapeutic alternatives for the treatment of heart failure; for example, a study showed that a spiro cycloalkane one induce positive inotropic activity via phosphodiesterase inhibition in an animal model [22]. Other report showed that the compound OPC-18790 is a positive inotropic and vasodilating agent which increases intracellular cyclic AMP and stimulates intracellular Ca +2 currents in an isolated dog heart model [23]. In addition, a study indicated that the compound YS-49…”