Cardiomyopathy of doxorubicin in experimental animals, Factors affecting the severity, distribution and evolution of myocardial lesions.

Heart lesions induced in mice, rats, rabbits and dogs by Doxorubicin administered i.v. according to various schedules were studied by light and electron microscopy Vacuolization of myocardial cytoplasm due to distention of the sarcoplasmic reticulum, the T-tubule system and the Golgi vesicles was one of the most common findings. Myocytolysis, clumping and loss of fibrils, fragmentation of sarcomeres, swelling of mitochondria and an increase in lysosomes and residual bodies were also observed. The severity of the cardiomyopathy, quantitatively evaluated by a score system, proved to be dose-dependent. Cardiomyopathy was more severe when the treatment was given in a short period by administration of high doses than when the same cumulative dose was administered as low doses repeated for a long period. The left atrium was more severely affected than the ventricles when high doses were given, whereas it was less affected in animals given low doses. The cardiomyopathy was less severe in animals receiving the same dose in a high volume of solvent and during a long perfusion time. Threshold doses were needed both to induce the cardiomyopathy and to establish it as a progressive disease.