Protection from adriamycin-induced cardiomyopathy in rats.
The use of adriamycin, one of the most potent antineoplastic agents available causes a dose dependent cardiomyopathy. Carnitine does play a central role in myocardial metabolism by controlling fatty acid oxidation and the acetyl-CoA pool. Protective effects of carnitine have been described in different myocardial diseases. We therefore investigated whether chronic carnitine administration could protect from adriamycin-induced cardiomyopathy. As the rat has proved to be an effective model for adriamycin-induced cardiomyopathy, we studied four groups of rats, treated for 6 weeks according to the following protocols: group (I) adriamycin i.v. and carnitine i.p. (II) adriamycin i.v. and NaCl i.p. (III) NaCl i.v. and i.p. (IV) NaCl i.v. and carnitine i.p. After 6 weeks of treatment, hearts were studied in an isolated working rat heart system. Adriamycin/NaCl treated hearts produced reduced cardiac output and left ventricular systolic pressure compared to controls (NaCl/CaCl, group III) or to adriamycin/carnitine treated hearts (Fig. 1-3 and Table 1). The myocardial carnitine content in non-perfused hearts was not influenced by adriamycin therapy, and muscle, kidney and liver carnitine levels were unchanged. However, total plasma carnitine in the adriamycin/NaCl group was significantly elevated, based on increased carnitine esters. Histological changes like degeneration, vacuolization, interstitial edema, fibrosis and mitochondrial damage were pronounced in the adriamycin group but were almost lacking in the carnitine-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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Metabolic Research Laboratory, William S. Middleton Memorial Veterans Administration Hospital, Madison.
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D002331:Carnitine / Q000627:therapeutic use*; D004317:Doxorubicin; D008297:Male; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D004317:Doxorubicin; D002331:Carnitine