Extracellular matrix remodeling in coxsackievirus B3 myocarditis

The connective tissue abnormality in relation to T lymphocytes was investigated in murine myocarditis. Inbred BALB/c-nu/+ (euthymic and normal T cell function) and BALB/c-nu/nu (athymic and T cell deficient) mice were inoculated with coxsackievirus B3 (CB3). Hearts were stained with hematoxylin-eosin, Malloryazan, and silver impregnation, for reticulin fiber abnormalities, and T lymphocyte subsets. In BALB/c-nu/+ mice, active myocardial necrosis appeared parallel with T lymphocyte infiltrates, that is, it was absent on day 0, increased until 14 days, and then decreased with time. In contrast, the abnormal reticulin fiber architecture and interstitial fibrosis increased with time until 60 days, when ventricular remodeling was noted. In the hearts of BALB/c-nu/nu mice, although minimal myocardial necrosis associated with infiltrating immature T lymphocytes was noted earlier, subsequent interstitial fibrosis and reticulin fiber abnormalities were not documented later. The abnormal reticulin fiber architecture seen in BALB/c-nu/+ mice may contribute to the extracellular matrix remodeling in murine CB3 myocarditis in which dilated cardiomyopathy develops later.