Cyclophosphamide-induced cardiomyopathy in the rat.

Cyclophosphamide given to ACI inbred rats produced histologic evidence of cardiomyopathy and degenerative vascular changes beginning as early as 4 days after the first of three 150-mg/kg doses (0.9 g/m2). The interval between doses was 14 days to allow bone marrow to recover after each treatment. Twofold increases in heart weight and DNA content were observed 56 days after initial treatment; compensatory hypertrophy and a marked infiltration of the myocardium by lymphocytes were observed histologically at that time. Heart weight and DNA content were again at control levels on Day 126. Hydroxyproline content, which increased along with DNA and weight, did not decrease until after Day 196, confirming a morphologic finding of increased fibrosis after cyclophosphamide which eventually decreased in severity. These data re-emphasize the necessity for considering both the acute and chronic toxic effects, as well as recovery, when developing treatment schedules employing therapeutically effective chemotherapeutic agents.