Study of mechanisms and effects of sodium 5-hydroxydecanoate on experimental ischemic ventricular arrhythmia

Abstract

We investigated the effects of sodium 5-hydroxydecanoate (5-HD) on experimentally induced ischemic arrhythmia and its mechanisms of action by biochemical and electrophysiological techniques. 5-HD, at the single dose of 200 mg/kg (p.o.) or at the one week multiple doses of 3 to 100 mg/kg (p.o.), suppressed the incidence of ventricular fibrillation induced by coronary ligation in rats. 5-HD at the dose of 3 or 10 mg/kg (i.v.) elevated the ischemically decreased ventricular fibrillation threshold in the coronary ligated dogs. In isolated rat heart, 5-HD suppressed the K⁺ release from ischemic myocardium at the doses of 10^-5 to 10^-3M. 5-HD at the dose of 10^-4M decreased the open state probability of ATP regulated K⁺ channel in isolated myocardial cell of guinea pig. Contents of highenergy-phosphate compounds were markedly decreased in ischemic myocardium of rats, and they were not affected by 5-HD. These results demonstrate the efficacy of 5-HD against experimental ischemic ventricular arrhythmia. Its antiarrhythmic action may be attributed, at least in part, to the suppression of K⁺ release from ischemic myocardium by possibly inhibiting the ATP regulated K⁺ channel.