1、Ischemia-reperfusion Injury Pathophysiology Department, Tongji Medical College, HUST1;1. Concepts: Ischemia-reperfusion (I-R) injury, oxygen/calcium/pH paradox, calcium overload, no-flow phenomenon2. Causes and conditions of I-R injury3. Mechanisms of I-R injury4. Metabolic and functional alteration

2、s5. Prevention and treatment principleContents2;Aggravated ischemic injury during reperfusion Reperfusion Injury3;Ischemia Components4;5;0 hrReperfusionIschemic Injury of Neurons1 hr2 hr6;IschemiaTimeInjuryDeathInjury WindowsReperfusionOxygen paradox, calcium paradox, pH paradox7;Causes and Conditio

3、ns of Reperfusion InjuryCausesConditionsRecover from cardiac arrestOrgan transplantationLysing thrombiIschemia timeBranch circulationOxygen consumptionTemperature, Na+, pH, Ca2+8;Case PresentationA 50-year-old man was admitted to the hospital with severe chest pain of 5 hours duration. Mental confus

4、ion and in acute dyspnea. HR: 110 beats/min, sinus rhythm;BP: 75/50 mmHg;ECG: ST segment elevation, V1-V6LVEF: 31% Improvement in breathBP: 100/70 mmHgLVEF: 38%Temporary ventricular tachycardiaDiuretic, tissue plasminogen activatorBalloon angioplasty?9;Mechanisms of Reperfusion InjuryFree radicalsCa

5、2+iNeutrophil activation and Others10;Free radicalAny atom or molecule possessing unpaired electronsSuperoxide anion (O2.-)Hydroxyl radical (OH.)Nitric oxide (NO.)Peroxynitrite （ONOO- )( 過氧亞硝酸鹽）Lipid peroxide radical (LOO.)Oxygen free radicalsReactive oxygen species (ROS) Oxygen free radicalsHydroge

6、n peroxide Others11;1. Mitochondria2. Activated inflammatory cells3. Nitric oxide4. Ionizing radiationFormation of ROS12;Reperfusion Ca2+iROSMechanism 1O213; Xanthine oxideseReperfusionIschemiaATPCa2+iXanthine dehydrogenaseHypoxanthinexanthineO2Uric acid AMPO2O2.- H2O2Endothelial cellMechanism 214;I

7、schemiaReperfusionO2Pro-inflammatory mediators(e.g. cytokines)NOONOO-O2- (Respiration burst)Mechanism 315;Biochemical Impacts of ROS16;17;Calcium OverloadThe abnormal increase of intracellular calcium which causes cell injury 18;Mechanism 1ReperfusionIschemia ATP Membrane depolarizationCa2+Na+Na/Ca

8、exchanger19; Ca2+Na+ReperfusionH+H+ Na+IschemiaCa2+Na+Mechanism 2H+Na/H exchanger20;ReperfusionCa2+Na+H+Na+a1NAPLCPIDGPKCIP3SRCa2+Mechanism 321;Mechanism 4ReperfusionMitochondriaERSRCa2+22;23;Na+i Gene activation Neutrophil activation Neutrophil Activation and Others24;Neutrophil activation ROSInfla

9、mmatorymediatorsInjury of Micro-vessels No-reflow phenomenonCell injuryRole of NeutrophilReperfusion 25;Structural and Functional Changes Reperfusion arrhythmiaMyocardial stunningHeart:Brain:EdemaCell death26;27;Electrocardiographic Alterations Associated with the Three Zones of Myocardial Infarction28;Heart InjuryIschemia-reperfusion injuryCalcium overload Free radical Destroy of contractile protein Myocardial stunningCa+ K+ Na+ArrhythmiaCell death29;Brain Injury30;31;Principles of Prevention and Treatment Control of reperfusion conditionsRemoval of free