Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease

Linda A. Jelicks, Madhulika Chandra, Jamshid Shirani, Vitaliy Shtutin, Baiyu Tang, George J. Christ, Stephen M. Factor, Murray Wittner, Huan Huang, Louis M. Weiss, Shankar Mukherjee, Boumediene Bouzahzah, Stefka B. Petkova, Mauro M. Teixeira, Stephen A. Douglas, Maria L. Loredo, Pedro D'Orleans-Juste, Herbert B. Tanowitz

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1497-1506
Number of pages10
JournalInternational Journal for Parasitology
Volume32
Issue number12
DOIs
StatePublished - Nov 2002

Keywords

  • Cardiac magnetic resonance imaging
  • Chagas' disease
  • Echocardiography
  • Endothelin
  • Endothelin-converting enzyme
  • Mice
  • Neutral endopeptidases
  • Phosphoramidon
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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    Jelicks, L. A., Chandra, M., Shirani, J., Shtutin, V., Tang, B., Christ, G. J., Factor, S. M., Wittner, M., Huang, H., Weiss, L. M., Mukherjee, S., Bouzahzah, B., Petkova, S. B., Teixeira, M. M., Douglas, S. A., Loredo, M. L., D'Orleans-Juste, P., & Tanowitz, H. B. (2002). Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease. International Journal for Parasitology, 32(12), 1497-1506. https://doi.org/10.1016/S0020-7519(02)00136-4