The influence of amrinone on cardiac toxicity induced by adriamycin in rats.

The influence of amrinone (AM), a positive inotropic drug, on cardiotoxicity induced by repeated adriamycin (ADR) administration, was studied in rats. AM, administered at various doses, did not affect rat body weight gain, heart rate, electrocardiographic parameters (QRS complex, S alpha T segment, T-wave), or the histological cardiac picture. By contrast, ADR markedly inhibited rat body weight increase and induced the appearance of early ECG alterations, especially S alpha T widening, as well as morphological cardiac changes consisting of macrovacuolation of myocytes, atrophy, necrosis and fibrosis. When given with ADR, AM reduced the toxicity of ADR limiting the deleterious effects of the drug on body weight gain and delaying the appearance of ECG abnormalities, particularly S alpha T widening and T-wave flattening. The severity of cardiac lesions histologically evaluated at the end of the experiment, however, was similar in rats given ADR or AM plus ADR. These results may be explained by taking into account the ability of AM to increase the Ca2+ influx through the slow channels in myocardial cells, thus counteracting the decreased inward slow Ca2+ currents due to ADR. The failure of AM to improve histological cardiac alterations significantly, seems to indicate that among the numerous pathogenetic mechanisms of ADR-induced cardiotoxicity, the changes in cellular Ca2+ fluxes play an important, but not a fundamental role.