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.