Evaluation of the effects of low molecular weight heparin on inflammation and collagen deposition in chronic coxsackievirus B3-induced myocarditis in A/J mice.
Coxsackievirus, Group B, type 3 (CVB3) infection of A/J male mice induces chronic myocarditis with increased interstitial fibrosis and collagen deposition. Heparin, a naturally occurring sulfated glycosaminoglycan, has both anti-inflammatory and antifibrotic activities besides its well-known anticoagulant activity. This study determined whether heparin treatment could decrease either cardiac inflammation or fibrosis in chronic CVB3-induced myocarditis. Control mice were either untreated or treated with heparin (4 micrograms/g body weight, subcutaneously 5 times weekly) beginning 2 days before infection of other groups. Additional groups received either virus only (1 x 10(4) plaque-forming units [PFU]), virus followed by heparin beginning 14 days after CVB3 inoculation, or virus and heparin beginning 2 days before CVB3 inoculation. Animals were sacrificed 14, 28, and 58 days after infection. Heparin treatment begun either before or after virus inoculation reduced animal mortality by approximately 20%. Heparin did not alter virus infection or replication in the heart. Histologically, only animals treated with heparin before virus inoculation showed reduced myocardial inflammation, and only at day 58. However, heparin treatment begun either before or after virus infection significantly decreased collagen deposition in the heart (fibrosis).
Frizelle
S
S
Department of Pathology, University of Vermont, Burlington 05405.
Schwarz
J
J
Huber
S A
SA
Leslie
K
K
D000818:Animals; D003094:Collagen / Q000032:analysis* / Q000378:metabolism; D003384:Coxsackievirus Infections; D029822:Enterovirus B, Human / Q000302:isolation & purification / Q000502:physiology*; D005355:Fibrosis; D006495:Heparin, Low-Molecular-Weight / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008970:Molecular Weight; D009205:Myocarditis / Q000378:metabolism / Q000382:microbiology*; D009206:Myocardium / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology
D006495:Heparin, Low-Molecular-Weight; D003094:Collagen