Effects of early and late verapamil administration on the development of cardiomyopathy in experimental chronic Trypanosoma cruzi (Brazil strain) infection.
Chagas' disease, caused by Trypanosoma cruzi, leads to acute myocarditis and chronic cardiomyopathy. Myocardial structure and function were evaluated in T. cruzi (Brazil strain)-infected CD1 mice by histopathology, cardiac gated magnetic resonance imaging (MRI) and transthoracic echocardiography. There was a significant reduction in inflammation and fibrosis in infected mice treated early in infection. In mice treated late in infection, echocardiography revealed a significant increase in the end diastolic diameter and a decrease in percent fractional shortening and relative wall thickness. MRI revealed an increase in the right ventricular internal dimension. These findings, consistent with a dilated cardiomyopathy, were ameliorated in the early but not in the late treatment group, demonstrating that late treatment with verapamil is ineffective in reversing the development of chagasic cardiomyopathy in chronically infected mice. Our data underscore the hypothesis that early events determine the progression to cardiomyopathy and that early treatment with verapamil can prevent such progression.
Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Andrea P
AP
De Souza
Herbert B
HB
Tanowitz
Madhulika
M
Chandra
Vitaliy
V
Shtutin
Louis M
LM
Weiss
Stephen A
SA
Morris
Stephen M
SM
Factor
Huan
H
Huang
Murray
M
Wittner
Jamshid
J
Shirani
Linda A
LA
Jelicks
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology; D002598:Chagas Cardiomyopathy / Q000517:prevention & control*; D014355:Chagas Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D009205:Myocarditis / Q000473:pathology; D018512:Parasitemia; D014700:Verapamil / Q000008:administration & dosage* / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D014700:Verapamil