Myocardial fibrin deposition in experimental viral myocarditis that progresses to dilated cardiomyopathy.
Myocardial fibrosis is a characteristic late feature in cases of viral myocarditis that progress to dilated cardiomyopathy. However, the pathogenesis of the myocardial fibrosis in such cases is unknown. Prior studies have shown that in healing wounds and tumor stroma generation, interstitial fibrin deposition precedes the development of fibrosis. Therefore, interstitial fibrin deposition in the myocardium was investigated in a murine model of myocarditis in which dilated cardiomyopathy develops. Inbred male C3H/He mice inoculated with coxsackievirus B3 were killed 0, 3, 7, 14, 21, 30, and 60 days after infection. Paraffin sections of hearts were stained with hematoxylin-eosin, Masson's trichrome stain, and antibodies to fibrinogen/fibrin by use of an immunoperoxidase technique. Pretreatment of all mice with anticoagulants and antifibrinolytics 5 minutes before death was used to prevent artifactual fibrin deposition and fibrinolysis during tissue manipulation. Tissue fixation in formalin supplemented with acetic acid served to extract non-cross-linked fibrin, fibrinogen, and fibrinogen and fibrin degradation products, thus ensuring that clotted and cross-linked fibrin was the major immunoreactant. Myocardial fibrin deposition and fibrosis were each quantitated by computer-assisted image analysis. Myocardial fibrin deposition first appeared on day 3, was maximal on day 14, and disappeared by day 30. Conversely, myocardial fibrosis was not detectable until day 14 and was maximal at day 60. Thus, as in healing wounds and developing tumor stroma, fibrin deposition preceded fibrosis in this murine model of myocarditis that progresses to dilated cardiomyopathy.
Schnitt
S J
SJ
Department of Pathology, Beth Israel Hospital, Boston, MA 02215.
Stillman
I E
IE
Owings
D V
DV
Kishimoto
C
C
Dvorak
H F
HF
Abelmann
W H
WH
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000209:etiology*; D003384:Coxsackievirus Infections; D004801:Eosine Yellowish-(YS); D005337:Fibrin / Q000378:metabolism*; D005355:Fibrosis; D006416:Hematoxylin; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling
D005337:Fibrin; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin