Carnitine protection against adriamycin-induced cardiomyopathy in rats.
The effects of chronic adriamycin toxicity on myocardial carnitine content and contractile function were studied in rats, along with potential protective effects of L-carnitine administration. Cardiomyopathy was induced over a 6- to 7-week period by weekly intravenous injections of adriamycin, 2 mg/kg. In vivo myocardial tissue levels of carnitine were not significantly changed by adriamycin, but plasma levels were elevated. Cardiac output was depressed in isolated perfused hearts from adriamycin-treated rats perfused with 11 mM glucose. In a second experiment, 4-week-old male rats were divided into four groups: saline-treated control, L-carnitine-treated control, saline-treated adriamycin, and L-carnitine-treated adriamycin. L-Carnitine was given intraperitoneally each day at a dose of 500 mg/kg. Myocardial histology and ultrastructure were analyzed. Cardiac performance was determined in hearts perfused with 1.2 mM palmitate and 5.5 mM glucose. Hearts from saline-treated adriamycin rats showed histopathological changes and a significantly diminished cardiac output at various preloads when compared to saline-treated controls. Daily intraperitoneal L-carnitine reduced histopathological alterations and improved cardiac performance.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002331:Carnitine / Q000378:metabolism / Q000627:therapeutic use*; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D004317:Doxorubicin; D002331:Carnitine