Anti‐arrhythmic effects of (‐)‐carnitine chloride and its acetyl analogue on canine late ventricular arrhythmia induced by ligation of the coronary artery as related to improvement of mitochondrial function

Abstract

1Using the two-stage coronary ligation method, first described by Harris, (1950), anti-arrhythmic effects (AAE) of (-)-carnitine chloride (LCC) and acetyl (-)-carnitine chloride (ALCC) were studied in conscious unrestrained dogs in comparison with those of disopyramide (D). Two-stage ligation of the coronary artery resulted in a significant decrease in the myocardial free carnitine content.2 Intravenous administration of LCC (300mg kg-') and D (5 mg kg-') suppressed the ventricular arrhythmia induced by coronary ligation after 24 hours. ALCC (300 mg kg-') was found to be less potent.3 An improvement of the mitochondrial function (respiratory control index (RCI) and oxidative phosphorylation rate (OPR)) was noted with LCC and ALCC and there was a linear correlation between AAE expressed as reduction of arrhythmic ratio and improvement in the OPR, whereas there was no improvement in mitochondrial function after D. 4 Plasma carnitine concentration was increased after administration of LCC, attaining the value of around 8 mm at 10 min after 300 mg kg-'. At 60 min, the plasma carnitine concentration was still about half as high as at 10 min. After ALCC, both acetyl carnitine and free carnitine were found in the plasma. The concentration of the former was decreased after attaining a peak value of around 0.2 mm at 10 min, while the plasma concentration of free carnitine was gradually increased. 5 The anti-arrhythmic effects of LCC and ALCC were ascribed to the improvement of mitochondrial oxidative phosphorylation, while effects other than the improvement of the mitochondrial activity were suggested as mechanisms of anti-arrhythmic effects of D.

Lack of correlation between the antiarrhythmic effect of l‐propionylcarnitine on reoxygenation‐induced arrhythmias and its electrophysiological properties

“…It has been reported that exogenous administration of L-carnitine may counteract the myocardial depletion of endogenous carnitine stores, resulting in myocardial protection (Liedtke & Nellis, 1979;Liedtke et al, 1982). L-Carnitine has also been reported to exert antiarrhythmic activity on ventricular arrhythmias caused by coronary ligation and/or reperfusion in the dog (Suzuki et al, 1981;Kobayashi et al, 1983;Imai et al, 1984). Recently, it has been shown that Lpropionylcarnitine (L-PC) protects the ischaemic myocardium more than L-carnitine or L-acetylcarnitine (Paulson et al, 1986).…”