An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following TraumaHemorrhage 英文参考文献.docVIP

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An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following TraumaHemorrhage 英文参考文献.doc

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An Adequately Robust Early TNF-α Response Is a Hallmark of Survival Following TraumaHemorrhage 英文参考文献

AnAdequatelyRobustEarlyTNF-aResponseIsa HallmarkofSurvivalFollowingTrauma/Hemorrhage RajaieNamas1,AliGhuma1,AndresTorres1,PatricioPolanco1,HernandoGomez1,DerekBarclay1 ,Lisa Gordon1,SvenZenker2,3¤,HyungKookKim2,LindaHermus1,RubenZamora1,MatthewR.Rosengart1, GillesClermont2,3,AndrewPeitzman1,TimothyR.Billiar1,3,JuanOchoa1,3,MichaelR.Pinsky2,3 ,Juan CarlosPuyana1,2,3,YoramVodovotz1,3 * 1DepartmentofSurgery,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2DepartmentofCriticalCareMedicine,UniversityofPittsburgh, Pittsburgh,Pennsylvania,UnitedStatesofAmerica,3CenterforInflammationandRegenerativeModeling,McGowanInstituteforRegenerativeMedicine,Universityof Pittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract Background: Trauma/hemorrhagic shock (T/HS) results in cytokine-mediated acute inflammation that is generally considereddetrimental. Methodology/PrincipalFindings:Paradoxically,plasmalevelsoftheearlyinflammatorycytokineTNF-a(butnotIL-6,IL-10, or NO2-/NO3-) were significantly elevated within 6h post-admission in 19 human trauma survivors vs. 4 non-survivors. Moreover,plasmaTNF-awasinverselycorrelatedwithMarshallScore,anindexoforgandysfunction,bothinthe23patients takentogetherandinthesurvivorcohort.Accordingly,wehypothesizedthatifanearly,robustpro-inflammatoryresponse weretobeamarkerofanappropriateresponsetoinjury,thenindividualsexhibitingsucharesponsewouldbepredisposed to survive. We tested this hypothesis in swine subjected to various experimental paradigms of T/HS. Twenty-three anesthetizedpigsweresubjectedtoT/HS(12HS-onlyand11HS+Thoracotomy;meanarterialpressureof30mmHgfor 45–90min)alongwithsurgery-onlycontrols.Plasmaobtainedatpre-surgery,baselinepost-surgery,beginningofHS,and every15minthereafteruntil75min(intheHSonlygroup)or90min(intheHS+Thoracotomygroup)wasassayedfor TNF-a, IL-6, IL-10, and NO2-/NO3-. Mean post-surgery6HS TNF-a levels were significantly higher in the survivors vs. non- survivors,whilenon-survivorsexhibitednomea