ATTENUATION OF CARDIOTOXICITY OF DAUNOMYCIN USING A COMPLEX WITH HEPARIN

Daunomycin (DM) is one of the most important antitumor agents, However , the cardiotoxicity of DM limits it's clinical use, We have made an i onic complex with heparin to decrease the cardiotoxicity. Cardiotoxici ties of DM and DM-heparin complex were compared in hamsters. On the el ectrocardiogram (ECG), two of the four hamsters given DM showed the se rious abnormality, bidirectional ventricular premature contraction, wh ile the hamsters given DM-heparin or saline had no abnormalities. On p athological examination, cardiac tissue in hamsters given DM showed de position of basophilic materials, mild eosinophilic change of myofibri ls and microvacuolization, whereas no change was observed in hamsters given DM-heparin complex or saline. Acute toxic effects on survival ra tes and body weights were more profound in DM-infused mice than in DM- heparin-infused mice. DM and DM-heparin complex showed similar antican cer activity both in vivo and in vitro. Thus, the present study sugges ts that the DM-heparin complex may attenuate the cardiotoxicity of DM without affecting it's antitumor effect in humans.