Searching for mechanisms that matter in early septic acute kidney injury an experimental study 英文参考文献.docVIP

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Searching for mechanisms that matter in early septic acute kidney injury an experimental study 英文参考文献.doc

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Searching for mechanisms that matter in early septic acute kidney injury an experimental study 英文参考文献

Benesetal.CriticalCare2011,15:R256 /content/15/5/R256 RESEARCH OpenAccess Searchingformechanismsthatmatterinearly septicacutekidneyinjury:anexperimentalstudy JanBenes1,JiriChvojka2,RomanSykora2,JaroslavRadej2,AlesKrouzecky2,IvanNovak2andMartinMatejovic2* Abstract Introduction:Inalmosthalfofallsepsispatients,acutekidneyinjury(AKI)develops.However,thepathobiologic differencesbetweensepsispatientswithandwithoutAKIareonlypoorlyunderstood.Weusedaunique opportunitytoexaminedynamicinflammatory,renalhemodynamic,andmicrovascularchangesintwoclinically relevantlarge-animalmodelsofsepsis.Ouraimwastoassessvariabilityinrenalresponsestosepsisandtoidentify bothhemodynamicandnonhemodynamicmechanismsdiscriminatingindividualswithAKIfromthoseinwhom AKIdidnotdevelop. Methods:Thirty-sixpigswereanesthetized,mechanicallyventilated,andinstrumented.Afterarecoveryperiod, progressivesepsiswasinducedeitherbyperitonitis(n=13)orbycontinuousintravenousinfusionoflive Pseudomonasaeruginosa(n=15).Eightshamoperated-onanimalsservedastime-matchedcontrols.Allanimals receivedstandardintensivecareunit(ICU)care,includinggoal-directedhemodynamicmanagement.Before,andat 12,18,and22hoursofsepsis,systemicandrenal(ultrasoundflowprobe)hemodynamics,renalcortex microcirculation(laserDoppler),inflammation(interleukin-6(IL-6),tumornecrosisfactor-alpha(TNF-a ),oxidative stress(thiobarbituricacidreactivespecies(TBARS),nitrite/nitrateconcentrations(NOx),andrenaloxygenkinetics andenergymetabolismweremeasured. Results:In14(50%)pigs,AKIdeveloped(62%inperitonitis,40%inbacteriainfusionmodel).Fecalperitonitis resultedinhyperdynamiccirculation,whereascontinuousbacteriainfusionwasassociatedwithnormodynamic hemodynamics.Despiteinsultsofequalmagnitude,comparablesystemichemodynamicresponse,anduniform supportivetreatment,onlythosepigswithAKIexhibitedaprogressiveincreaseinrenalvascularresistance.This intrarenalvasoconstrictionoccurredpredominantlyinthelive-bacteriainfusionmodel.IncontrasttoAKI-free animals,thedevelopmentofsepticAKI