title: Pathologic changes in the cardiac interstitium of mice infected with encephalomyocarditis virus.
abstract: Patients with myocarditis often develop dilated cardiomyopathy and congestive heart failure. Histologically, myocarditis is manifested by rare foci of myocyte necrosis with interstitial inflammation, while cardiomyopathy is characterized by diffuse interstitial fibrosis, myocyte hypertrophy, and an absence of active interstitial inflammation. The relationship between myocardial inflammation and interstitial fibrosis is poorly understood. This relationship was examined in mice that developed a diffuse interstitial inflammation of the heart over a period of 21 days following infection with encephalomyocarditis virus. Typical early lesions (day 7) included focal zones of myocytolysis containing mononuclear and polymorphonuclear inflammatory cells that were associated with the focal loss of reticular fibers. Later pathology (days 14-21) was characterized by a sparse, diffuse interstitial myocarditis with little ongoing necrosis. Changes within the myocardial interstitium remote from healing necrotic foci were marked by reticular fiber thickening and disorganization, often associated with pleomorphic fibroblasts. Reticulin fiber deposition was quantitatively increased in sparsely inflamed regions of hearts from infected animals as compared to noninflamed regions from the same hearts (p < 0.005) or hearts of control animals (p < 0.001). Scanning electron microscopy revealed interstitial changes that were more extensive than indicated by routine staining with hematoxylin and eosin for Masson's trichrome. The progressive changes within the cardiac interstitium during the development of postmyocarditic cardiomyopathy suggest that direct viral infection of fibroblasts or an interaction between the interstitium and inflammatory cells and their secreted products may contribute to pathologic changes within the interstitial collagen matrix.
authors.affiliation: Department of Immunology and Infectious Disease, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Neumann
authors.affiliation: Department of Immunology and Infectious Disease, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Wulff
authors.affiliation: Deparment of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: M K
authors.initials: MK
authors.lastname: Leppo
authors.affiliation: The Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Love
authors.affiliation: Department of Immunology and Infectious Disease, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Rose
authors.affiliation: Department of Immunology and Infectious Disease, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA; Deparment of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Herskowitz