Abstract

The direct myocardial action of daunomycin and related compounds was studied in artificial perfusate or blood-perfused isolated dog hearts. Samples of perfusate for paper and thin-layer chromatography were collected at intervals of 1, 5, 15, 30 and 60 minutes. In these experiments daunomycin (50 mg) caused an increase in coronary perfusion pressure and at the same time a metabolite, daunomycinone, was formed. When hearts were perfused with a Ringer's solution for 60 minutes the same dose of daunomycin caused only slight increases in perfusion pressure and little daunomycinone was formed. The injection of 50 or 18 mg of daunomycinone into blood-perfused heart preparations caused an immediate increase in coronary perfusion pressure. Adriamycin (50 mg) produced effects on the coronary vasculature almost identical to daunomycin, whereas N-acetyldaunomycin (50 mg) caused no deleterious effects. Adriamycin was found to be broken down to a daunomycinone-like product in a manner similar to daunomycin, whereas significantly less conversion of N-acetyldaunomycin was detected. These experiments tend to indicate that a significant amount of daunomycin and adriamycin is converted to a daunomycinone-like product in the blood and this metabolite may be responsible for the coronary artery constriction observed in the blood-perfused isolated heart preparations.