Prolonged propionyl-L-carnitine pre-treatment of rabbit: Biochemical, hemodynamic and electrophysiological effects on myocardium

Recently it has been reported that prolonged treatment with propionyl-l-carnitine, a carnitine derivative, results in a positive inotropic effect. To gain further insight into its mode of action, we pre-treated 253 rabbits for up to 10 days with daily doses of 1 mmol/kg propionyl-l-carnitine or l-carnitine intraperitoneally, using saline-treated animals as control. Twenty-four hours after the last injection, we isolated papillary muscles for electrophysiological investigations. Whole hearts were used in perfusion experiments for biochemical and hemodynamic measurements. In addition, mitochondria were harvested from these hearts for the analysis of their function. Plasma and cardiac levels of free carnitine, along with plasma short-chain acylcarnitines, increased at least two-fold after treatment with carnitine or its propionyl-ester, with concomitant rises in tissue long-chain acylcarnitine and long-chain acyl-CoA. At the time of animal sacrifice, treatment did not increase plasma or tissue propionyl-l-carnitine content. The studies carried out with perfused hearts and isolated mitochondria failed to show an effect of propionyl-l-carnitine pre-treatment on high-energy phosphate metabolism or respiration. Papillary muscles from animals, treated for 10 days, showed a lengthening of the action potential duration from 63 ± 4 to 102 ± 6 ms (P