Ganciclovir and cidofovir treatment of cytomegalovirus-induced myocarditisin mice

The cardiovascular disease myocarditis is characterized by inflammation and necrosis of cardiac muscle. This disease has been associated with various viral etiologies, including cytomegalovirus (CMV), Murine CMV (MCMV) infect ion of adult BALB/c mice produces a disease with acute and chronic phases s imilar to that found in humans. In our murine model, we have investigated t he therapeutic efficacy of antiviral drug administration on myocarditis. Tw o drugs commonly used for CMV treatment, ganciclovir and cidofovir, were su bjected to trials, with both drugs showing potent antiviral activity agains t MCMV both in vitro and in vivo. The acute phase of myocarditis was signif icantly reduced when antiviral therapy commenced 24 h postinfection. Such t reatment also reduced the severity of the chronic phase of myocarditis, In contrast, antiviral treatment commenting after the acute phase had no effec t on chronic myocarditis, Reinfection of mice with MCMV caused exacerbation of myocardial inflammation. Such an increase in severity of myocarditis co uld be prevented with either ganciclovir or cidofovir treatment, but the pr eexisting inflammation and necrosis of the myocardium persisted. These data highlight possible therapeutic uses of antiviral drugs in viral myocarditi s as well as further elucidating the pathogenic nature of the disease.