EFFECTS OF PIRARUBICIN IN COMPARISON WITH EPIRUBICIN AND DOXORUBICIN ON THE CONTRACTILE FUNCTION IN RAT ISOLATED CARDIAC MUSCLES

1. We have examined the effects of pirarubicin (THP), compared with ep irubicin (EPI) and doxorubicin (DXR), on the contractile function in p apillary muscles isolated from rats. 2. In in vitro experiments, in wh ich the rat was treated once a week for 4 weeks with DXR (total dose 1 0 mg/kg) and thereafter once a week for 4 weeks with THP, EPI or DXR ( total dose 10 mg/kg), a positive instead of negative force-frequency r elationship was observed in the muscles treated with EPI and DXR, but not with THP, and an increase in contractile response to extracellular Ca2+ was observed more markedly in the muscles treated with DXR than in those treated with EPI and THP. 3. In in vitro experiments, in whic h the muscle preparations were incubated with the drugs at 100 or 200 mu M for 2 hr, EPI and DXR caused a negative inotropic effect and a pr olongation of tension duration, while THP caused a slight positive ino tropic effect and a Slight prolongation of tension duration. 4. Furthe rmore, a decrease in the potentiated postrest contraction was observed more markedly in the muscles incubated with EPI and DXR at 200 mu M t han in those with THP. 5. These results suggest that both EPI and DXR show a cardiotoxicity by impairing the function of cardiac sarcoplasmi c reticulum, and that the switching of the treatment from DXR to THP p roduces less impairing effects.