ISOPROTERENOL CARDIOTOXICITY IN THE DUCKLING

Isoproterenol is a synthetic catecholamine which has been associated with cardiotoxicity in some human patients. Rats injected with isoproterenol have been used as a model of this cardiotoxicity. The objectives of the present studies were: (i) to establish if isoproterenol is cardiotoxic in ducklings (ii) to characterize the gross, histopathologic, and ultrastructural myocardial alterations produced in treated ducklings, and (iii) to study the effects of feeding furazolidone (FZ) and intramuscular injection of selenium-vitamin E (Se-E) on isoproterenol-induced toxicosis in ducklings. Ducklings developed isoproterenol-induced cardiotoxicity and showed increased susceptibility to isoproterenol with advancing age and elevated environmental temperature. The LD(,50) for isoproterenol was 360 mg/kg at 23(DEGREES)C. Resistance to enhanced cardiotoxicity developed when multiple isoproterenol injections were given. Clinical alterations of isoproterenol toxicosis in ducklings included dyspnea, tachypnea, anorexia, weight loss, recumbency and death. Plasma creatine kinase activity was not significantly elevated. Pale areas were observed in the ventricular myocardium grossly. These foci had myocardial necrosis and mineralization on histopathologic study. Ultrastructural alterations in the myocardium at 12 hours postinjection were myofibrillar lysis, z-band streaming and electron-dense matrical granules in mitochondria. Hypercontracted and necrotic myocytes with mineralized mitochondria were observed at 24 hours postinjection. Macrophage infiltration was initially observed at 48 hours postinjection. Myocyte dedifferentiation was present 48 hours postinjection but mitotic activity was not observed. These findings indicate that sublethally-injured myocytes of ducklings may undergo repair but no evidence of myocyte regeneration was seen following myocyte necrosis. The spectrum of myocardial morphologic alterations produced in ducklings by isoproterenol was similar to that described in various mammalian species. Intramuscular selenium-vitamin E injection (0.25 mg Se as selenite and 68 I.U. alpha tocopheryl acetate/kg) given 24 hours prior to isoproterenol did not provide protection against the cardiotoxicity. Feeding furazolidone (400 mg/kg of diet) for 10 days prior to isoproterenol significantly increased mortality but did not increase myocardial damage scores in survivors. These findings suggest that isoproterenol cardiotoxicity is not mediated via free radical injury