Published online before print April 21, 2003, doi: 10.1161/01.CIR.0000062690.79456.D0
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(Circulation. 2003;107:2264.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease
From the Departments of Pathology and Microbiology-Immunology and the Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Correspondence to David M. Engman, Northwestern University Feinberg School of Medicine, Dept of Pathology, 303 E Chicago Ave, Ward 6-175, Chicago, IL 60611. 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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