PMID- 21851968
OWN - NLM
STAT- MEDLINE
DCOM- 20120611
LR  - 20111128
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 128
IP  - 6
DP  - 2011 Dec
TI  - Treatment with unfractionated heparin attenuates coagulation and inflammation in 
      endotoxemic mice.
PG  - e160-5
LID - 10.1016/j.thromres.2011.07.044 [doi]
AB  - INTRODUCTION: 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 mul 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-alpha, IL-1beta and TAT in plasma at 3 
      and 6h; 2) Pretreatment of mice with UFH inhibited the expression of TNF-alpha, IL-1beta 
      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. CONCLUSION: These 
      data suggest that UFH attenuates inflammation and coagulation and prevents 
      lethality in endotoxemic mice.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Ding, Renyu
AU  - Ding R
AD  - Departments of Intensive Care Unit, The First Affiliated Hospital of China 
      Medical University, Shenyang, Liaoning Province, China.
FAU - Zhao, Dongmei
AU  - Zhao D
FAU - Guo, Renxuan
AU  - Guo R
FAU - Zhang, Zhidan
AU  - Zhang Z
FAU - Ma, Xiaochun
AU  - Ma X
LA  - eng
PT  - Journal Article
DEP - 20110817
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Anticoagulants)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Blood Coagulation/*drug effects
MH  - Cytokines/metabolism
MH  - Endotoxemia/blood/*drug therapy/metabolism/pathology
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Inflammation/blood/*drug therapy/metabolism/pathology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Random Allocation
MH  - Shock, Septic/blood/*drug therapy/pathology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2011/08/20 06:00
MHDA- 2012/06/12 06:00
CRDT- 2011/08/20 06:00
PHST- 2011/05/12 00:00 [received]
PHST- 2011/06/23 00:00 [revised]
PHST- 2011/07/25 00:00 [accepted]
PHST- 2011/08/20 06:00 [entrez]
PHST- 2011/08/20 06:00 [pubmed]
PHST- 2012/06/12 06:00 [medline]
AID - S0049-3848(11)00416-6 [pii]
AID - 10.1016/j.thromres.2011.07.044 [doi]
PST - ppublish
SO  - Thromb Res. 2011 Dec;128(6):e160-5. doi: 10.1016/j.thromres.2011.07.044. Epub 
      2011 Aug 17.