Antiarrhythmic effects of 1-carnitine and its acetyl derivative in beagle dogs and improvement of the mitochondrial function.

Abstract

Using two-stage coronary ligation method (Harris’ method), antiarrhythmic effects (AAE) of 1-carnitine and acetyl-1-carnitine (ALCC) were studied in conscious unrestrained dogs in comparison with those of disopyramide (D). 1-Carnitine (LC)(300 mg/kg i.v.) and 1-carnitine chloride (LCC)(300 mg/kg i.v.) and D (5 mg/kg i.v.) suppressed the ventricular arrhythmia induced by coronary ligation, while 1-carnitine phosphate (LCP) had no effects. ALCC was found to be antiarrhythmic, though less potent. An improvement of the mitochondrial function (respiratory control index, RCI and oxidative phosphorylation rate, OPR) was noted with all the drugs used except LCP, and there was a linear correlation between AAE expressed as reduction of arrhythmic ratio and improvement of mitochondrial function with LC, LCC and ALCC. All drugs except D elevated cardiac LC contents and lowered FFA and long chain acyl carnitine. AAE of LC and LCC was ascribed to the improvement of mitochondrial lipid metabolism, while effects other than the improvement of the mitochondrial lipid metabolism are invoked to explain the failure of LCP and the low potency of ALCC to produce AAE.