Postcoxsackievirus B3 Myocardiopathy in Mice

“Idiopathic myocardiopathy” in man may represent a sequel to an antecedent coxsackievirus infection. To test this hypothesis and to elucidate the possible pathogenetic mechanisms involved, the following studies were performed. Weanling mice were inoculated ip with 3 × 104 TCID50 of coxsackievirus B3 (Nancy). Five days later myocarditis could be demonstrated by viral isolation from the heart and by the presence of acute inflammation, necrosis and early mineralization. Thirty days after infection when the virus could no longer be recovered, the inflammatory response continued although there was evidence of simultaneous healing. Six months later there was extensive fibrosis and calcification, but scattered foci of chronic inflammation persisted. Delayed hypersensitivity to cardiac and viral antigens was studied in these mice by the macrophage migration inhibition method. Thirty days after infection no delayed hypersensitivity could be demonstrated to antigens prepared from a crude saline extract of normal mouse myocardium, from the myocardium of mice with acute coxsackievirus carditis, or to inactivated coxsackievirus B3. Coxsackievirus B3 antigens were found in the myocardium of acutely infected animals by the indirect fluorescent antibody technique. However, no such antigens were detectable 6 mo after infection in animals with chronic inflammation. Thus, there is no evidence that delayed hypersensitivity to either viral or cardiac antigens or that persistence of viral antigens in the myocardium play a role in the pathogenesis of the postviral chronic myocarditis of mice. It is more likely that this myocardiopathy in the mouse represents a sequel to replacement fibrosis which accompanies healing of the acute cytolytic phase of viral infection.