N-3脂肪酸在急重症的应用VIP免费

N-3LipidsinCriticalCareMedicineDr.KonstantinMayerUniversityofGiessenLungCenterPulmonaryandCriticalCareMedicineUniversityHospitalGiessenandMarburg第一页，共五十一页。LipidMediatorSynthesisAA(-6)-degranulationleakage-adhesionvasoconstrictionPMN-activationpostkapillaryLOCOLTE4LTD4LTB4LTC4PGI2TxA2vasodilatationvasoconstriction5,6-EET8,9-EET11,12-EET14,15-EETvasodilatation(?)othereffects?EDHF(?)P450第二页，共五十一页。Impactofn-3vs.n-6FattyAcidsonInflammation第三页，共五十一页。KeyFeaturesofAcuteLungInjurypulmonaryhypertensionVQ-mismatch/Shunt•vasomotordysfunction•vascularleakagegasexchangesecundarybacterialinvasionQO2O2O2•leukocyteinvasionCapillarysequestrationAlveolarinvasionN-3Lipids第四页，共五十一页。•Randomized,controlledstudy•21PtswithsepticARDS•LCTorLCT/MCT@12g/h•Pulmonaryhemodynamics/Ventilationparameter第五页，共五十一页。ResultsLCT(n-6)•IncreaseinPulmonaryArteryPressure(MPAP)•DecreaseinOxygenation-Index(PaO2/FiO2)第六页，共五十一页。Grimminger,Mayeretal.JPharmExpTher1993,AmJPhysiol1995第七页，共五十一页。AmJRespCellMolBiol1997AmJRespCritCareMed1997,AmJPhysiol2000Protectiveimpactofn-3fattyacidsonedema-formationinamodelofsepticlungfailureLTB4++++LTB4++LTB4+LTB5++++第八页，共五十一页。EffectsofParenteralApplicationofFishOilversusSoyBeanOilEmulsionsonBacterialClearanceFunctionsI.Kelbel,T.Koch,A.Prechtl,A.Heller,E.Schlotzer,H.G.Schiefer,H.NeuhofInfusionTherapy&TransfusionMedicine:26,226-232,1999第九页，共五十一页。ExperimentalProtocol(Kelbeletal.,1999)Design:36rabbits,randomlyassignedto6groupsTreatment:1.5g/kgb.w./dayfor3daysofa-fishoilemulsion(n-3rich)-asoybeanoilemulsion(n-6rich)or-0.9%saline(Control)E.coliintravenousinjection(1.3x108CFU)Sacrificeofanimals3or6hafterbact.injectionParameters:Bacterialcountsinlung,liver,spleen&kidney第十页，共五十一页。NumberofbacterialcoloniesinthelungKelbeletal.1999第十一页，共五十一页。Long-termlipid-infusioninmice第十二页，共五十一页。LeukocyteInvasioninaModelofAcuteLungInjury–Impactofn-3LipidsLPS*CritCareMed2007BALBronchoalveolarlavageLPSlipopolysaccharide第十三页，共五十一页。Enteraln-3lipids+anti-oxidants:N-3Lipids&ARDS•RCTof146criticallyillpatients•acutelunginjuryandpositivebronchoalveolarlavageforleukocytes•Double-blinded•Enteral:N-3Lipidsvs.highfatdiet•Gadek,CritCareMed1999;27:1409第十四页，共五十一页。ARDS–Enteraln-3LipidsAdaptedfrom:GadekJE.etal.,CritCareMed1999;27:1409-20p=.011p=.016第十五页，共五十一页。Dolipidsmodulateacutelunginjury?Shouldwehavefaithinfat?KeyFeaturesofARDSpulmonaryhypertensionVQ-mismatch/Shunt•vasomotordysfunction•vascularleakagegasexchangesecundarybacterialinvasionQO2O2O2•leukocyteinvasionCapillarysequestrationAlveolarinvasionLipidemulsionsareamainstayofparenteralnutritionusedinmanyventilatedpatientswithacutelunginjury第十六页，共五十一页。ImmunologicEffectsoflipidemulsionsinARDS•n-3lipidsmayhavebeneficialeffectsinARDSincontrastton-6lipids.•SCCM+CanadianGuidelines:–N-3+ARDS:GradeArecommendation第十七页，共五十一页。N-3lipidsandbacterialtranslocation/bacterialkilling?Endo/ExotoxinFocusBacterialtranslocationnosocomialPneumonia1.barrierdysfunctionGut2.barrierdysfunction第十八页，共五十一页。Improvementofbloodflowintheintestineinendotoxicratsbyn-3lipidsL=SBOL-M=SBO+MCTFO-20=L-M+FO(20%)FO-40=L-M+FO(40%)Pscheidl,Eetal第十九页，共五十一页。Improvement...