Abstract
Tissue culture and murine experimental models were employed to study the mechanism by which Coxsackie B virus might cause severe focal necrosis of human cardiac tissue. Human studies included the comparison of the incidence of recent Coxsackie B virus infection in patients suffering acute myocardial infarction with sex and age matched controls and, the immunofluorescent and electron microscopic examination of heart biopsy material. The severity of cardiac lesions in mice was shown to be directly associated with the integrity of the T-lymphocyte response following Coxsackie B4 virus inoculation. The cytolytic action of serum was not demonstrated in infected mice but the cytotoxicity of activated T-lymphocytes against chronically infected "carrier" cells was shown. Hyperimmune serum from adult male CBA/ca strain mice exhibited a cytotoxic in vitro reaction against homologous heart endothelial tissue chronically infected with Coxsackie B4 virus. This specific serum cytotoxicity was removed after heat inactivation of serum complement proteins at 56°C and reinstated following addition of Guinea-Pig complement. The degree of observable cytotoxicity decreased when serum from donor mice of a heterologous strain was used. Serum levels of creatine kinase where shown to increase following viral inoculation of mice but marked increase in specific isoenzyme MB levels occured only following T-cell mediated damage. Comparison of serum antibody response between patients with acute myocardial infarction, and age and sex matched controls revealed no significant differences in the incidence of serologically diagnosed recent Coxsackie B virus infection. High concomitant serum antibody titres were however associated with acute myocardial infarction more frequently than any other cardiac disease. Human cardiac damage was also shown to be associated with the presence of Coxsackie B viral antigen. However, whilst human studies have revealed no conclusive evidence to suggest a relationship between Coxsackie B virus infection and acute myocardial infarction, experimental studies have demonstrated a mechanism by which viruses of the Coxsackie B group could cause severe focal cardiac damage.