ELECTROLYTE AND MORPHOLOGIC ALTERATIONS OF MYOCARDIUM IN ADRIAMYCIN-TREATED RABBITS

Abstract

Rabbits receiving adriamycin (ADR) on a chronic schedule developed significant histopathologic, ultrastructural and tissue electrolyte alterations of the ventricular myocardium. Rabbits that developed clinicopathologic evidence of cardiomyopathy with ADR had histologic lesions of the myocardium, including perivascular fibrosis, interstitial fibrosis and edema and myocytolysis. Ultrastructurally, large vacuoles resembling distended sarcoplasmic reticulum displaced the contractile elements and mitochondria, which were diminished in number within affected myocytes. Frequently, mitochondria appeared as electron-dense structures surrounded by layers of membranes resembling myelin figures. In addition, rabbits with cardiomyopathy had marked elevations in ventricular Ca, Na and H(2)O concentrations. Serum electrolytes were not significantly elevated, but lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were significantly increased, indicative of a cardiomyopathy. Rabbits receiving ADR but not developing clinicopathologic evidence of heart failure also had significant elevations in ventricular Ca, Na and H(2)O. Rabbits with no cardiomyopathy had no increases either in serum electrolyte concentrations or CPK and LDH levels. These studies indicate that marked increases in ventricular tissue Ca precede and accompany morphologic evidence of chronic myocardial degeneration and may be instrumental in the development of the ADR-induced cardiomyopathy.