Treatment of viral myocarditis with ribavirin in an animal preparation.

Abstract

The therapeutic effects of ribavirin, a broad-spectrum, antiviral agent, on experimental myocarditis caused by encephalomyocarditis (EMC) virus were investigated. Four-week-old DBA/2 mice were inoculated with 10 plaque-forming units (pfu) of EMC virus. Ribavirin in a dose of 100 (group 1, n = 20), 200 (group 2, n = 10), or 400 mg/kg/day (group 3, n = 10) was administered subcutaneously on days 0 to 12 after virus inoculation, and animals were observed for 12 days. Control animals were injected with saline (n = 20). Mice treated with ribavirin survived longer than controls (mean survival 6.7 days for group 1, 7.4 days for group 2, 7.7 days for group 3, and 5.2 days for control; p less than .005). Myocardial virus titers on days 6 to 8 were significantly lower in group 2 (3.24 +/- 0.49 log10pfu/mg; p less than .005) and in group 3 (1.70 +/- 0.65 log10 pfu/mg; p less than .001) compared with controls (4.09 +/- 0.57 log10 pfu/mg). The incidence of gross myocardial lesions was significantly lower in group 1 (13/20, 65%), group 2 (2/10, 20%), and group 3 (0/20, 0%) compared with controls (20/20, 100%) (p less than .05). Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups; there was less infiltration in groups 2 and 3 (p less than .01) and less severe necrosis in group 3 (p less than .01). Thus ribavirin effectively inhibited myocardial virus replication and reduced the inflammatory response and myocardial damage in an experimental preparation of viral myocarditis.