PATHOGENESIS OF EARLY-STAGE OF ADRIAMYCIN CARDIOMYOPATHY .3. PUMP FUNCTION AND ENERGY-METABOLISM OF THE HEART

Rats were given 3 injections of 2 mg/kg of doxorubicin (Adriamycin) wi th daily intervals. In 1-2 weeks after the last injection hearts were excised and isolated hearts were perfused in nuclear magnetic resonanc e spectrometer. Elevation of perfusion pressure from 60 to 120 mm Hg w as followed by augmentation of coronary flow velocity and of pressure developed under isovolumic conditions. Maximal values of coronary flow velocity and heart rate-developed pressure product related to unit of weight were higher in hearts of adriamycin treated rats compared to c ontrol by 50 and 31%, respectively. Levels of ATP and phosphocreatine in myocardium of these animals did not differ from control at any perf usion pressure. Rate of oxygen consumption by mitochondria in skinned muscular fibers of adriamycin treated rats was similar to control both in ADP-free medium and at maximal stimulation of respiration after ad dition of ADP. But index of respiratory control was significantly towe red by 30% and apparent constant of affinity for ADP -- by 35% compare d to control values. The latter fact was indicative of stable augmenta tion of permeability of mitochondrial membranes.