Effects of OPC-18790, a new positive inotropic agent, on canine ventricular arrhythmias.
OPC-18790 is a positive inotropic and vasodilating agent that increases 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 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.
Wu
Z
Z
Department of Pharmacology, Yamanashi Medical University, Japan.
Awaji
T
T
Abe
H
H
Motomura
S
S
Hashimoto
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy; D010042:Ouabain / Q000494:pharmacology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000188:drug therapy*; D014664:Vasodilation / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000139:chemically induced
D002316:Cardiotonic Agents; D015363:Quinolones; C077543:toborinone; D010042:Ouabain; D004837:Epinephrine