缺血再灌注損傷

Ischemia-reperfusionInjury(缺血再灌注損傷）CasePresentationA50-year-oldmanwasadmittedtothehospitalwithseverechestpainof5hoursduration.Mentalconfusionandinacutedyspnea

（呼吸困難）.HR:110beats/min,sinusrhythm;BP:75/50mmHg;ECG:STsegmentelevation,V1-V6LVEF:31%X-ray:grosspulmonaryedemaImprovementinbreathBP:100/70mmHgLVEF:38%Temporaryventriculartachycardia（心律不齊）diuretic,tissueplasminogenactivatorBalloonangioplastyQuestion:whytachycardiaoccurredafteroperation?IschemicInjuryisenhancedduringreperfusionReperfusionInjuryOxygenparadox,calciumparadox,pHparadoxIschemiaComponents0hrReperfusionIschemicInjuryofNeurons1hr2hrIschemiaTimeInjuryDeathInjuryWindowsReperfusionReperfusioninjuryRecoverEarlyreperfusionDelayedreperfusionPersistentperfusiondeficit<6hr24hrCausesandConditionsofReperfusionInjuryCausesConditionsRecoverfromcardiacarrestOrgantransplantationLysingthrombiIschemiatimeBranchcirculationOxygenconsumptionTemperature,Na+,pH,Ca2+MechanismsofReperfusionInjuryFreeradicals↑Ca2+i↑OthersFreeradicalAnyatomormoleculepossessingunpairedelectronsSuperoxideanion(O2.-)Hydroxylradical(OH.)Nitricoxide(NO.)Peroxynitrite（ONOO-

)(

過氧亞硝酸鹽）ˉLipidperoxideradical(LOO.)ˉOxygenfreeradicalsReactiveoxygenspecies(ROS)

OxygenfreeradicalsHydrogenperoxideOthers1.Mitochondria2.Activatedinflammatorycells3.Nitricoxide4.IonizingradiationFormationofROSReperfusion↑Ca2+iROSMechanism1↑

Xanthine

oxideseReperfusionIschemiaATP↑Ca2+iXanthine

dehydrogenase↑HypoxanthinexanthineO2↓Uricacid↑AMPO2O2.-

H2O2EndothelialcellMechanism2IschemiaReperfusionO2Pro-inflammatorymediators(e.g.cytokines)NOONOO-O2.-(Respirationburst)Mechanism3BiochemicalImpactsofROSCalciumOverloadTheabnormalincreaseofintracellularcalciumwhichcausescellinjuryMechanism1ReperfusionIschemia↓ATPMembranedepolarizationCa2+↑Na+Na/Caexchanger↑Ca2+Na+Reperfusion↓H+H+↑Na+IschemiaCa2+Na+Mechanism2↑H+Na/HexchangerReperfusionCa2+Na+H+Na+a1NAPLCPIDGPKCIP3SRCa2+Mechanism3Mechanism4ReperfusionMitochondriaERSR↑Ca2+↑Na+i

GeneactivationNeutrophilactivation

OthersNeutrophilactivation

ROSInflammatorymediatorsInjuryofMicro-vesselsNo-reflowphenomenonCellinjuryRoleofNeutrophilReperfusionStructuralandFunctionalChangesReperfusionarrhythmiaMyocardialstunningEdemaHeart:Brain:CelldeathElectrocardiographicAlterationsAssociatedwiththeThreeZonesofMyocardialInfarctionHeartInjuryIschemia-reperfusioninjuryCalciumoverloadFreeradicalDestroyofcontractileproteinMyocardialdysfunctionCa++K+Na+ArrhythmiaCelldeathBrainInjuryPrinciplesofPreventionandTreatmentControlofreperfusionconditionsRemovaloffreeradicalsUseofcalciumantagonistsUseofcellprotectionreagentsTreatmentofedemaO2.-OH.SODGSHONOO-LOO.TOHLOOHH2ORemovalofROSCasePresentationA50-year-oldmanwasadmittedtothehospitalwithseverechestpainof5hoursduration.Mentalconfusionandinacutedyspnea.HR:110beats/min,sinusrhythm;BP:75/50mmHg;ECG:STsegmentelevation,V1-V6LVEF:31%X-ray:grosspulmonaryedemaImprovementinbreathBP:100/70m