Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease
International Journal for Parasitology
Chagas' disease is an important cause of cardiomyopathy. Endothelin-1, a vasoactive peptide has been implicated in the pathogenesis of chagasic cardiomyopathy. C57BL/6×129sv and CD1 mice were thus, infected with trypomastigotes of Trypanosoma cruzi (Brazil strain) and these infected mice were compared with infected mice treated with phosphoramidon. This compound inhibits endothelin-converting enzyme and neutral endopeptidases and does not affect the growth of the parasite in culture. Phosphoramidon was given in a dose of 10mg/kg for the initial 15 days post-infection None of the C57Bl/6×129sv mice died as a result of infection. However, there was marked myocardial inflammation and fibrosis in infected, untreated mice. The hearts of the infected, phosphoramidon-treated mice showed significantly less pathology. Cardiac magnetic resonance imaging of infected mice revealed right ventricular dilation that was less severe in those treated with phosphoramidon. Phosphoramidon-treated CD1 mice survived the acute infection. Transthoracic echocardiography demonstrated left ventricular dilation and reduced percent fractional shortening and relative wall thickness. These alterations were also attenuated as a result of phosphoramidon treatment. These data suggest that endothelin-1 contributes to the pathogenesis of chagasic cardiomyopathy and interventions that inhibit the synthesis of endothelin-1 and/or neutral endopeptidase might have a protective effect on myocardial structure and function in murine Chagas' disease. © 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.
Jelicks, Linda A.; Chandra, Madhulika; Shirani, Jamshid; Shtutin, Vitaliy; Tang, Baiyu; Christ, George J.; Factor, Stephen M.; Wittner, Murray; Huang, Huan; Weiss, Louis M.; Mukherjee, Shankar; Bouzahzah, Boumediene; Petkova, Stefka B.; Teixeira, Mauro M.; Douglas, Stephen A.; Loredo, Maria L.; D'Orleans-Juste, Pedro; and Tanowitz, Herbert B., "Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease" (2002). Department of Cardiovascular Medicine Articles & Publications. 84.