Long-term 1-carnitine treatment prolongs the survival in rats with adriamycin-induced heart failure.
BACKGROUND
The most serious consequence of heart failure is the shortened life expectancy, which may be associated with myocardial energy starvation.


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.
Kawasaki
N
N
First Department of Internal Medicine, Fukui Medical School, Japan.
Lee
J D
JD
Shimizu
H
H
Ueda
T
T
D000214:Acyl Coenzyme A / Q000032:analysis*; D000255:Adenosine Triphosphate / Q000032:analysis*; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002331:Carnitine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D046508:Culture Techniques; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010725:Phosphocreatine / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate
D000214:Acyl Coenzyme A; D010725:Phosphocreatine; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D002331:Carnitine