Background: The most serious consequence of heart failure is the shortened life expectancy, which may be associated with myocardial energy starvation.
Methods and results: Eight-week-old male Sprague-Dawley rats received 6 intraperitoneal injections of adriamycin (group A: total dose; 15 mg/kg body weight) or vehicle (group C) over 2 weeks. Rats then received either 272 mg/kg daily of oral 1-carnitine (A-LC and C-LC groups) or saline (A-S and C-S groups) for 6 weeks. The cumulative mortality rate in the A-LC group was significantly lower than in the A-S group (13 vs 42%, P = .028). Myocardial levels of high-energy phosphate compounds (ATP and creatine phosphate) and fatty acid metabolites (free carnitine, short-chain and long-chain acylcarnitine, and long-chain acyl CoA) in the left ventricle were measured the day after the last dose of drug or vehicle was administered. ATP was decreased by 73%, creatine phosphate by 61%, free carnitine by 52%, short-chain acylcarnitine by 48%, and long-chain acylcarnitine by 56% in the A-S group compared to the C-S group. Long-chain CoA was increased by 168% in the A-S group. Levels of myocardial high-energy phosphate compounds and fatty acid metabolites were near normal in adriamycin- and 1-carnitine-treated rats.
Conclusions: Preservation of the myocardial level of carnitine by 1-carnitine treatment prolonged survival of rats with adriamycin-induced failure by improving the myocardial metabolism of fatty acids.