Delayed and progressive myocardial lesions after adriamycin administration in the rabbit

A cardiomyopathy similar to that observed in cancer patients after prolonged chemotherapy with adriamycin can be produced in the rabbit, characterized by mitochondrial and myofilamentous degeneration with noninflammatory myolysis and connective tissue repair. The progressive and delayed myocardial lesions produced in rabbits receiving increasing total doses of adriamycin were studied after 23, 35, 43, and 77 days of continuous treatment and in posttreatment periods up to 150 to 180 days after the last administration of adriamycin. Total adriamycin doses that produced increased serum enzyme, myocardial sodium, and calcium levels but that failed to elicit serious myocardial morphological lesions during the period of drug administration resulted in a delayed cardiomyopathy leaving focal areas of fibrosis and progressive lesions that became more severe after discontinuation of drug administration. These findings suggest that the myocardial effects of adriamycin are cumulative and potentially nonreversible.