title: Treatment with unfractionated heparin attenuates coagulation and inflammation in endotoxemic mice.
abstract: BACKGROUND
  In the pathogenesis of sepsis, inflammation and coagulation play a pivotal role. In addition to the anticoagulant activity, unfractionated heparin (UFH) has important immunomodulatory properties. However, different studies have reported conflicting effects on sepsis in association with heparin. The objective of this study is to determine whether UFH is able to reduce endotoxin-induced inflammation and coagulation in mice or produce improved outcome.
  
  
  METHODS
  C57BL/6J mice were randomly divided into two groups. Experimental mice were given intravenous injection of 8 units/20 g body weight UFH (heparin sodium) diluted in 20 μl sterile saline while the control mice received vehicle sterile saline only. They were injected with LPS (30 mg/kg, i.p.) 0.5h later. Blood was collected and Livers were harvested at 3 and 6h for analysis. In survival studies, a separate group of mice were treated with 8 units/20 g UFH (n=20) or sterile saline (n=20) given intravenously at 1, 12, 24 and 36 hours after LPS injection. Mice were monitored every 12 hours for a maximum of 72 hrs.
  
  
  RESULTS
  1) Pretreatment of mice with UFH strongly reduced the levels of TNF-α, IL-1β and TAT in plasma at 3 and 6h; 2) Pretreatment of mice with UFH inhibited the expression of TNF-α, IL-1β and tissue factor genes in blood cells at 3h; 3) UFH pretreatment dramatically diminished LPS-induced neutrophil sequestration (at 3 and 6h) , thrombi formation and fibrin(ogen) deposition in the liver (at 6h). 4) The UFH-pretreated group exhibited significantly lower levels of ALT and CRE at 6h. 5) Treatment with UFH could prevent mortality associated with endotoxin challenge.
  
  
  CONCLUSIONS
  These data suggest that UFH attenuates inflammation and coagulation and prevents lethality in endotoxemic mice.
authors.affiliation: Departments of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Renyu
authors.initials: R
authors.lastname: Ding
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.forename: Renxuan
authors.initials: R
authors.lastname: Guo
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin