Controversy still exists concerning the
therapy for viral
myocarditis which manifests a wide variety of clinical symptoms.
Vesnarinone, a
quinolinone derivative that was developed as a positive inotropic agent with complex actions, including
phosphodiesterase inhibition and
cation channel modification, has recently been confirmed to improve the prognosis of patients with chronic
heart failure. However, the precise mechanism of this beneficial effect is not yet clearly understood. In this study, using a murine model of acute viral
myocarditis resulting from encephalomyocarditis virus
infection, survival and myocardial damage were markedly improved by treatment with
vesnarinone. In contrast, survival was not improved by treatment with
amrinone, a
phosphodiesterase inhibitor. Although
vesnarinone did not inhibit viral replication or protect myocytes from viral direct cell injury, it did inhibit the increase in natural killer cell activity after
viral infection. On the other hand,
amrinone failed to inhibit natural killer cell activity. Both
vesnarinone and
amrinone suppressed the production of
tumor necrosis factor-alpha. Therefore, we postulate that
vesnarinone exerted its beneficial effects through an inhibition of natural killer cell activity, and that it serves as an
immunomodulator providing new therapeutic possibilities for the treatment of viral
myocarditis and/or immunological disorders.