Lessons from animal experiments in myocarditis

We have developed murine models of viral myocarditis induced by encephalomyocarditis (EMC) virus in which severe myocarditis, congestive heart failure and dilated cardiomyopathy occur in high incidence. From these models, we have learned the natural history and pathogenesis and assessed new diagnostic methods and therapeutic and preventive interventions. Mural thrombi in the atria and ventricles, ventricular aneurysms, conduction disturbance and various arrhythmias were seen in these models. Anti-heart antibody were found in sera of mice and myosin isoenzyme were changed during the course of EMC virus myocarditis. Atrial natriuretic polypeptide was markedly increased in the ventricles in these mice. Successive infection with coxsackievirus and EMC virus developed lesions similar to chronic myocarditis. The myocardial uptake of antimyosin antibody was proved to be a useful method of diagnosis of myocarditis. Treatment with the nucleoside analogue, ribavirin and recombinant alpha interferon effectively inhibited myocardial virus replication and reduced myocardial damage. Passive immunization and virus-specific vaccine prevented development of myocarditis. The use of immunosuppressive therapy was associated with greater mortality when administered early in illness and beneficial effects were not seen by later administration. Angiotensin-converting enzyme inhibitor improved myocardial injury and congestive heart failure. A nonselective beta-adrenergic blocker with intrinsic sympathomimetic activity, carteolol, prevented the development of myocardial lesions similar to those in dilated cardiomyopathy after myocarditis in the chronic stage.