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Journal of Cardiovascular Pharmacology and Therapeutics
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Prolonged Captopril Therapy in Murine Viral Myocarditis

Milagros P. Reyes

Division of Infectious Diseases, Wayne State University, Detroit, Michigan

Riad Khatib

St. John Hospital, Detroit, Michigan

Ghada Khatib

Grace Hospital, Detroit, Michigan

K.L. Ho

Henry Ford Hospital, Detroit, Michigan

Frederic Smith

Division of Infectious Diseases, Wayne State University, Detroit, Michigan

Robert A. Kloner

The Heart Institute, University of California, Los Angeles, California

Background: Acute myocarditis can progress to chronic heart muscle disease and cardiomyop athy. In the coxsackievirus B 3 (CB3) mouse model of myocarditis, early administration of cap topril, an angiotensin-converting enzyme (ACE) inhibitor, ameliorated histopathological changes in inflammation, necrosis, and calcification and reduced heart weight. Late administra tion of captopril reduced heart weight but did not affect the histological findings. In this study, we investigated the effects of prolonged captopril treatment in the chronic phase of this model.

Methods and Results: Three-week-old male CD1 mice were infected with CB3 and then randomized to receive placebo or captopril starting on day 7 of infection. Captopril, 2 g/L, was given as the drinking water daily for up to 6 months. Autopsies were performed at 6 and 10 months. Heart-to-body weight ratios were obtained, and deaths were tallied. Myocardial fibrosis was graded according to a score system. In addition, picrosirius red stain (PSR) also was used for assessment of collagen deposition. Mean heart weights were similar in both groups. Mean body weight was significantly lower in captopril-treated mice (40.7 g) than in the untreated group (43.6 g) at 6 months (P = .0155), and mortality was higher (8.7 vs 0.87%; P = .009). At 6 months, the mean myocardial fibrosis score in treated mice (0.12) was significantly less than in untreated animals (0.35; P = .035). With PSR, the mean myo cardial fibrosis score in the captopril group (1.20) was also significantly less than in the untreated group (1.58; P = .045). At 10 months, fibrosis scores were similar in both groups.

Conclusions: Chronic captopril treatment in CB3 myocarditis reduces myocardial fibrosis.

Key Words: chronic heart muscle disease • mouse cardiomyopathy • ACE inhibitors • viral cardiomyopathy.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 3, No. 1, 43-49 (1998)
DOI: 10.1177/107424849800300106


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CirculationHome page
J. S. Leon, K. Wang, and D. M. Engman
Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease
Circulation, May 6, 2003; 107(17): 2264 - 2269.
[Abstract] [Full Text] [PDF]



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