Electron microscopy study on the cardiac muscle of rats after adriamycin administration

ABSTRACT

A delayed cardiomyopathy, similar to that observed in cancer patients treated with the anthracycline antibiotic, adriamycin, was produced in the rat. Thirty animals were employed, divided into control and experimental groups which include the recovery period. A single dose of 6 mg/kg and cumulative dose of 15 mg/kg [six injections of 2.5 mg/ kg over two weeks] were administered intraperitoneally to the rats. In both doses, this syndrome was characterized by congestion of the myocardial vessels and focal to disseminated myofiber degeneration and necrosis. Alterations in myocardial cells were characterized by degeneration of mitochondria accompanied by myofibrillar breakdown and myolysis. The spectrum of myofiber alterations observed suggests two possible mechanisms which might explain the pathogenesis of the lesions observed in myocardial cells of the treated animals. The interference of anthracycline antibiotic with DNA-dependent RNA synthesis and the presence of nucleolar alterations suggest that the mycoardial lesions may be related to abnormal subcellular necrobiosis and a subsequent failure of the cell to renew mitochondrial and myofibrillar proteins. The similarity of these lesions to those produced by a wide variety of myocardial and general cellular toxins also suggests that more direct injury to sarcoplasmic components may be important in the pathogenesis of adriamycin cardiomyopathy