Effect of 711389-S, a new antiarrhythmic agent, on myocardial energy metabolism in guinea-pigs and rats.
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.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology; D004562:Electrocardiography; D004734:Energy Metabolism / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010766:Phosphorylation; D011412:Propanolamines / Q000097:blood / Q000494:pharmacology*; D051381:Rats
D000889:Anti-Arrhythmia Agents; D011412:Propanolamines; D010042:Ouabain; C044492:711389-S; D004206:Disopyramide