Prevention of the Cardiotoxic Effects of Adriamycin and Daunomycin in the Isolated Dog Heart

Abstract

In the isolated, blood-perfused dog heart daunomycin (50 mg) or adriamy-cin (50 mg) induced significant increases in coronary perfusion pressure. This effect appeared to be related to the conversion of the parent compounds to aglycone metabolites similar to daunomycinone. Pretreatment of the heart with agents blocking the vasoactive actions of epinephrine, histamine, serotonin or acetylcholine did not prevent the alteration in coronary vascular resistance. In contrast, 100 mg of either EDTA or ICRF 159 prevented the marked increase in perfusion pressure and reduced the formation of aglycone metabolites. Chelation is a common property of the 2 agents suggesting that removal of certain cations may alter metabolism and reduce the toxicity of adriamycin and daunomycin.