title: Cardioprotective effects of phosphoramidon on myocardial structure and function in murine Chagas' disease.
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 x 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 x 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.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.forename: Madhulika
authors.initials: M
authors.lastname: Chandra
authors.forename: Jamshid
authors.initials: J
authors.lastname: Shirani
authors.forename: Vitaliy
authors.initials: V
authors.lastname: Shtutin
authors.forename: Baiyu
authors.initials: B
authors.lastname: Tang
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Factor
authors.forename: Murray
authors.initials: M
authors.lastname: Wittner
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Shankar
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Boumediene
authors.initials: B
authors.lastname: Bouzahzah
authors.forename: Stefka B
authors.initials: SB
authors.lastname: Petkova
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Douglas
authors.forename: Maria L
authors.initials: ML
authors.lastname: Loredo
authors.forename: Pedro
authors.initials: P
authors.lastname: D'Orleans-Juste
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
mesh_terms: D000818:Animals; D002598:Chagas Cardiomyopathy / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D006020:Glycopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects* / Q000469:parasitology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014349:Trypanosoma cruzi
chemical_list: D006020:Glycopeptides; D011480:Protease Inhibitors; C008890:phosphoramidon