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(-3) M. 5-HD at the dose of 10(-4) M decreased the open state probability of ATP regulated K+ channel in isolated myocardial cell of guinea pig. Contents of high-energy-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.