Published Online
on April 21, 2003

A more recent version of this article appeared on May 6, 2003

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Submitted on October 22, 2002
Accepted on January 21, 2003

Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease

Juan S. Leon BA, Kegiang Wang MD, and David M. Engman MD, PhD^*

From the Departments of Pathology and Microbiology-Immunology and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Ill.

^* To whom correspondence should be addressed. E-mail: d-engman{at}northwestern.edu.

Background--Captopril, an angiotensin-converting enzyme inhibitor, is commonly prescribed to patients with Chagas heart disease (CHD). There are few human studies and no animal studies on the effects of captopril in CHD. We investigated the effects of captopril on myocarditis and the host immune response to Trypanosoma cruzi in an experimental model of acute CHD.

Methods and Results--A/J mice infected with Brazil strain of T cruzi developed acute myocarditis by day 21 after infection, consisting of severe focal inflammation, necrosis, fibrosis, and T cruzi pseudocysts. Administration of captopril (5 mg/L in the water) significantly reduced necrosis and fibrosis in infected mice. Increasing the captopril dose also led to a decrease in inflammation. Captopril did not affect overall mortality but did delay death while having no effect on parasitemia or cardiac parasite load. Treatment did not affect humoral immunity against T cruzi or cardiac myosin (autoimmunity) but did decrease delayed-type hypersensitivity responses against both antigens. Interestingly, increasing the dose of captopril induced mortality in infected mice in a dose-dependent manner. Mortality was apparently not due to T cruzi because neither parasitemia nor cardiac parasitosis was affected. The combination of captopril and infection may have impaired renal function because these mice had increased water consumption, decreased body mass, and increased serum BUN/creatinine ratio.

Conclusions--Captopril ameliorates the myocarditis associated with acute T cruzi infection.

Key words: myocarditis • angiotensin • infection • collagen • myosin

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