Role of selective V2-receptor-antagonism in septic shock a randomized, controlled, experimental study 英文参考文献.docVIP
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Role of selective V2-receptor-antagonism in septic shock a randomized, controlled, experimental study 英文参考文献
Rehbergetal.CriticalCare2010,14:R200
/content/14/6/R200
RESEARCH
OpenAccess
RoleofselectiveV2-receptor-antagonisminseptic
shock:arandomized,controlled,experimentalstudy
SebastianRehberg1*,ChristianErtmer1,MatthiasLange1,AndreaMorelli2,ElbertWhorton3,MartinDünser4,
Anne-KatrinStrohh?cker1,ErikLipke1,TimGKampmeier1,HugoVanAken1,DanielLTraber5,MartinWestphal1
Abstract
Introduction:V2-receptor(V2R)stimulationpotentiallyaggravatessepsis-inducedvasodilation,fluidaccumulation
andmicrovascularthrombosis.Therefore,thepresentstudywasperformedtodeterminetheeffectsofafirst-line
therapywiththeselectiveV2R-antagonist(Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressinoncardiopulmonary
hemodynamicsandorganfunctionvs.themixedV1aR/V2R-agonistargininevasopressin(AVP)orplaceboinan
establishedovinemodelofsepticshock.
Methods:Aftertheonsetofsepticshock,chronicallyinstrumentedsheepwererandomlyassignedtoreceivefirst-
linetreatmentwiththeselectiveV2R-antagonist(1μg/kgperhour),AVP(0.05μg/kgperhour),ornormalsaline
(placebo,eachn=7).Inallgroups,open-labelnorepinephrinewasadditionallytitratedupto1μg/kgperminute
tomaintainmeanarterialpressureat70±5mmHg,ifnecessary.
Results:ComparedtoAVP-andplacebo-treatedanimals,theselectiveV2R-antagoniststabilizedcardiopulmonary
hemodynamics(meanarterialandpulmonaryarterypressure,cardiacindex)aseffectivelyandincreased
intravascularvolumeassuggestedbyhighercardiacfillingpressures.Furthermore,leftventricularstrokeworkindex
washigherintheV2R-antagonistgroupthanintheAVPgroup.Notably,metabolic(pH,baseexcess,lactate
concentrations),liver(transaminases,bilirubin)andrenal(creatinineandbloodureanitrogenplasmalevels,urinary
output,creatinineclearance)dysfunctionswereattenuatedbytheV2R-antagonistwhencomparedwithAVPand
placebo.TheonsetofsepticshockwasassociatedwithanincreaseinAVPplasmalevelsascomparedtobaseline
inallgroups.WhereasAVPplasmalevelsremainedconstantintheplacebogroup,infusionofAVPincreasedAVP
plasmalevelsupto149±21pg/mL.Notably,treatmentwiththeselectiveV2R-an
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