EFFECTS OF SK AND F 93479 ON EXPERIMENTALLY INDUCED VENTRICULAR ARRHYTHMIAS IN DOGS, RATS AND MICE

The effects of SK&F 93479, a potent histamine H2-receptor antagonist, on ventricular arrhythmias induced by coronary artery ligation in dogs and rats and by aconitine infusion in mice were investigated. SK&F 93479 in large doses, significantly prevented the occurrence of spontaneous ventricular fibrillation and the changes in ventricular fibrillation threshold following coronary artery ligation in dogs. In rats subjected to ligation of the main left coronary artery, it significantly reduced the incidence of ventricular fibrillation, and significantly prolonged the time of onset of ventricular tachycardia and ventricular fibrillation. Apparently, SK&F 93479 did not significantly alter the incidence or the time of onset of cardiac dysrhythmias caused by aconitine infusion in mice. Apparently SK&F 93479 lacks non-specific antiarrhythmic activity; its protective effects against coronary artery ligation may be mediated by its histamine H2-receptor antagonizing action. Evidently, histamine may contribute to the genesis of ventricular arrhythmias resulting from acute myocardial ischemia.