Cardiovascular Research

Prolonged Captopril Therapy in Murine Viral Myocarditis.

Authors: MP Reyes|||R Khatib|||G Khatib|||KL Ho|||F Smith|||RA Kloner

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Abstract

BACKGROUND: Acute myocarditis can progress to chronic heart muscle disease and cardiomyopathy. In the coxsackievirus B(3) (CB(3)) mouse model of myocarditis, early administration of captopril, an angiotensin-converting enzyme (ACE) inhibitor, ameliorated histopathological changes in inflammation, necrosis, and calcification and reduced heart weight. Late administration 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 CD(1) mice were infected with CB(3) 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 myocardial 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 CB(3) myocarditis reduces myocardial fibrosis.