缺血再灌注损伤课件.pptVIP

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,pHparadox

IschemiaComponents

0hrReperfusionIschemicInjuryofNeurons1hr2hr

IschemiaTimeInjuryDeathInjuryWindowsReperfusionReperfusioninjuryRecover

EarlyreperfusionDelayedreperfusionPersistentperfusiondeficit6hr24hr

CausesandConditionsofReperfusionInjuryCausesConditionsRecoverfromcardiacarrestOrgantransplantationLysingthrombiIschemiatimeBranchcirculationOxygenconsumptionTemperature,Na+,pH,Ca2+

MechanismsofReperfusionInjuryFreeradicals↑Ca2+i↑Others

FreeradicalAnyatomormoleculepossessingunpairedelectronsSuperoxideanion(O2.-)Hydroxylradical(OH.)Nitricoxide(NO.)Peroxynitrite（ONOO-)(過氧亞硝酸鹽）ˉLipidperoxideradical(LOO.)ˉOxygenfreeradicalsReactiveoxygenspecies(ROS)OxygenfreeradicalsHydrogenperoxideOthers

1.Mitochondria2.Activatedinflammatorycells3.Nitricoxide4.IonizingradiationFormationofROS

Reperfusion↑Ca2+iROSMechanism1

↑XanthineoxideseReperfusionIschemiaATP↑Ca2+iXanthinedehydrogenase↑HypoxanthinexanthineO2↓Uricacid↑AMPO2O2.-H2O2EndothelialcellMechanism2

IschemiaReperfusionO2Pro-inflammatorymediators(e.g.cytokines)NOONOO-O2.-(Respirationburst)Mechanism3

BiochemicalImpactsofROS

CalciumOverloadTheabnormalincreaseofintracellularcalciumwhichcausescellinjury

Mechanism1ReperfusionIschemia↓ATPMembranedepolarizationCa2+↑Na+Na/Caexchanger

↑Ca2+Na