Tissueinjurysuppressesfibrinolysisafterhemorrhagicshockinnonhumanprimates(rhesusmacaque)
AntoniR.Macko,PhD,HunterB.Moore,MD,AndrewP.Cap,MD,PhD,M.AdamMeledeo,PhD,ErnestE.Moore,MD,andForestR.Sheppard,MD,Houston,Texas.JTraumaAcuteCareSurg,,Volume82,Number4.DOI:10./TA..
背景
低灌注与纤溶亢进和失血导致的早期死亡相关,而组织损伤与纤溶抑制和器官衰竭导致的晚期死亡相关。我们尝试用非人灵长类动物(恒河猴,NHP)模型来解释损伤模式对纤溶表型的影响。
BACKGROUND
Hypoperfusionisassociatedwithhyperfibrinolysisandearlydeathfromexsanguination,whereastissuetraumaisassociatedwithHypo-fibrinolysisanddelayeddeathfromorganfailure.Wesoughttoelucidatetheeffectsofinjurypatternsonfibrinolysisphenotypesusinganonhumanprimate(NHP)model.
方法
NHPs被随机分为三个损伤组(n=8):失血性休克组(HS)采用股动脉置管放血,在60分钟时间对血压进行目标控制形成失血性休克;HS+组为失血性休克合并软组织损伤(自剑突开始制造15cm正中切口行成软组织损伤,左腿制造横跨股骨远端5cm切口并对骨骼肌进行钝性分离形成骨骼肌损伤);HS++组为失血性休克合并软组织损伤和股骨骨折。试验对动物进行分钟的复苏和监测,并于造模前、休克末、复苏末和分钟时采集血标本,检测乳酸(Lac)、凝血酶原时间(PT)、部分活化凝血酶原时间(APTT)、D二聚体、纤维蛋白原、AT-III、血管血友病因子(vWF)和粘弹性试验(ROTEM)。结果以均值±标准差形式表示,统计学方法采用双因素方差分析和t检验。
METHODS
NHPswererandomizedtothreeinjurygroups(n=8/group):60minutesseverepressure-targetedcontrolledhemorrhagicshock(HS);HS+softtissueinjury(HS+);orHS+softtissueinjury+femurfracture(HS++).Animalswereresuscitatedandmonitoredforminutes.Bloodsampleswerecollectedatbaseline,end-of-shock,end-of-resuscitation(EOR),andT=minutesforassessmentsof:severityofshock(lactate)andcoagulationviaprothrombintime,partialthromboplastintime,D-dimer,fibrinogen,antithrombin-III,vonWillebrandfactor,andviscoelastictesting(ROTEM).Resultsarereportedasmean±SEM;statistics:two-wayanalysisofvarianceandt-tests(significance:p0.05).
结果
各组间的失血量、PT、APTT、D二聚体、纤维蛋白原和vWF大体相同,ROTEM也没有明显差异。HS组复苏末时D-二聚体升至基值的三倍,而HS+组和HS++组在T=分钟时显著升高(p0.05)。与HS+和HS++组相比,HS组在复苏末时的D-二聚体/乳酸比率升高2.2倍(2.2±0.3,分别为1.1±0.3和1.1±0.2;p0.05),组织因子活化的纤维凝块30分钟溶解指数(LY30%)显著降低(分别为98±1%,±0%,±0%;p0.05)。
RESULTS
Bloodloss,prothrombintime,partialthromboplastintime,antith-rombin-III,fibrinogen,andvonWillebrandfactorwereequivalentamongGroupsandviscoelastictestingrevealedfewdifferencesthroughoutthestudy.D-dimerincreasedapproximatelythreefold,atEORintheHSgroup,andatT=minutesintheHS+andHS++groups(p0.05).AtEOR,intheHSgroup白殿的图片如何快速治疗白癜风
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