Effect of amrinone on anthracycline-induced lethal and cardiac toxicity in mice and rats

The protective role of amrinone against toxicity of anthracyclines was examined in both mice and rats. These two anthracyclincs were selected since they are characterized by different patterns of toxicity. In contrast to doxorubicin, the 4′-deoxy derivative did not cause delayed mortality. The results of this investigation indicate that amrinone is an effective protective agent against acute lethal events induced by both anthracyclines. However, the inotropic agent did not reduce the delayed mortality produced by doxorubicin. This parallels the apparent lack of prevention of doxorubicin-induced myocardial toxicity in CD rats, as determined by ECG changes and by morphologic alterations following multiple drug administrations. The administration of amrinone did not interfere with the antitumor activity of 4′-deoxy-doxorubicin against C-26 colon tumor.