Reduction of 4-epiadriamycin cardiotoxicity by milrinone, a new cardiotonic agent

Recently, several non-catecholamine, non-glycoside cardiotonic drugs have been described. New compounds include amrinone, sulmazole and milrinone. Milrinone, a close analogue of amrinone, is about 30 times more potent than amrinone. In attempts to alleviate anthracyclines toxicity, we have previously reported that amrinone and sulmazole reduced the negative inotropic effect of adriamycin and 4-epiadriamycin in isolated guinea pig atria. The present study reports the effects of 4-epiadriamycin on electrically driven isolated guinea pig left atrium, in normodynamic or hypodynamic conditions. Exposure for 60' to 4-epiadriamycin (100 micrograms/ml) caused a depression of contractile force and of maximal rate of contractile force (df/dt). The negative effects of 4-epiadriamycin are antagonized by milrinone at 20 micrograms/ml.