Effect of 711389-S, a New Antiarrhythmic Agent, on Myocardial Energy Metabolism in Guinea-Pigs and Rats

Abstract

Abstract The effect of 711389-S, a new antiarrhythmic agent, on myocardial energy metabolism was investigated using anaesthetized guinea-pigs and rats. 711389-S elevated the adenylate energy charge and phosphorylation potential in normal guinea-pig myocardium. Large doses also increased the myocardial lactate content with ECG abnormalities. The close relationship between rate-pressure product and the myocardial energy state under 711389-S treatments showed the suppression of energy consumption due to a decrease of work output. In guinea-pigs with arrhythmic myocardia induced by intravenous infusion of ouabain, 711389-S prevented the loss of high-energy phosphate compounds and the acceleration of anaerobic glycolysis concomitant with the effective antiarrhythmic property. In ischaemic myocardium produced by ligation of the coronary artery in rats, 711389-S suppressed the decreases of creatine phosphate, NAD+ and adenylate energy charge. Moreover, this agent effectively blocked the incidence of ventricular arrhythmias at an early stage following the ligation. In all of these actions, 711389-S was more effective than disopyramide, which is in the same class of antiarrhythmics. 711389-S was concluded to be a favourable antiarrhythmic agent offering beneficial action against arrhythmic and ischaemic metabolic changes in the myocardium.