Experimental coxsackie B virus myocarditis in mice: 18 month histopathological and virological study.

In a series of experimental studies to test the hypothesis that idiopathic cardiomyopathy in man represents a sequela of virus myocarditis, coxsackie B 1, 3 or 5 virus was inoculated into ICR mice with two different amounts, that is, a small amount (0.1 ml of 10(5.5) TCID50/ml) and a large amount (0.1 ml of 10(7.5) TCID50/ml). Histopathological and immunofluorescent studies of the heart, analysis of the antibody titers in sera and evaluation of the virus concentration in various organs including the heart were carried out in an acute (up to the 21st day) and chronic phase (up to the 18th month) of the experiment. A small amount of coxsackie B 1 or 5 virus did not cause myocarditis, while a large amount of either virus rarely induced mild myocarditis. A small amount of coxsackie B 3 virus frequently caused mild myocarditis without obvious residual pathologic changes of the heart, while a large amount of the same virus always caused acute and severe myocarditis. In these animals, acute myocardial changes are almost in agreement with those in previous investigations except for capillary thrombi. The virus was isolated from the heart with higher titers than from other organs and identified in some cardiocytes by immunofluorescent study until the 14th day. Neutralizing antibody in sera appeared on the 7th day and remained for several months. Approximately two thirds of these mice left no significant myocardial lesions, whereas about one third of them which probably had extensive myocardial lesions in the acute phase developed significant myocardial fibrosis with calcification in the chronic phase. These lesions appeared to become larger after the 6th month. In and around the fibrotic lesions, atrophy, hypertrophy and/or disarray of myocardial fibers were observed. These hearts did not show hypertrophy or dilatation but their histologic findings resembled those seen in some cases of congestive cardiomyopathy except for severe calcification in the myocardium.