Comparative Cardiac Toxicity of Daunomycin in Three Rodent Species ∗ †

Abstract

Summary

Daunomycin, an antibiotic used in the treatment of acute leukemia has been implicated in the development of a lethal cardiopulmonary syndrome. Rats, guinea pigs, and hamsters were studied to determine whether cardiac toxicity would be induced in animals. The rat was resistant to high doses of daunomycin (200–300 mg/kg) while fatal respiratory depression occurred in the guinea pig (75–175 mg/kg). In contrast 50 mg/kg induced acute cardiac alterations in the hamster consisting initially of changes in the ST segment, R and T waves followed by a bidirectional ventricular tachycardia. The arrhythmia in the hamster was daunomycin specific since both dactinomycin and cyclophosphamide has little cardiac effect whereas rubidomycin (50 mg/kg) produced comparable ECG effects. Bidirectional ventricular arrhythmias have been reported to occur in animals and humans as a sign of digitalis intoxication, however, this was not seen in the hamster after varying doses of ouabain. Both digitalis and daunomycin are glycosides but the present experiments tend to indicate they may induce cardiac toxicity in the hamster by different mechanisms.