PATHOGENESIS OF CARDIOMYOPATHY CAUSED BY ANTHRACYCLINE ANTIBIOTICS - EFFECT OF PULMONARY STENOSIS ON THE DEVELOPMENT OF CARDIOMYOPATHY

This study was undertaken to elucidate the effect of pressure load on the development of cardiomyopathy induced by daunorubicin in the right ventricle of rabbits on which pulmonary stenosis had been performed. The right ventricular pressure after occlusion of the pulmonary artery was approximately twice that prior to occlusion. Pulmonary stenosis a pparently produced hypertrophy of the right ventricular myocardium wit hin approximately 2 weeks of occlusion. In rabbits with pulmonary sten osis, the characteristic myocardial degenerative changes induced by da unorubicin were found on the right ventricular wall. However, in rabbi ts without pulmonary stenosis, myocardial lesions were observed only o n the left ventricular wall. The pressure load acting as a mechanical stress increases myocardial damage induced by daunorubicin. It is well known that anthracyclines take effect on cells in which nucleic acid synthesis is augmented and the pressure load results in the enhancemen t of protooncogene expression in myocytes and a subsequent increase in protein synthesis. These results suggest that the pressure load may p lay a significant role in anthracycline cardiomyopathy by increasing p rotein synthesis in the myocardium. (C) 1998 by Elsevier Science Inc.