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Ischemia-reperfusion Injury (缺血再灌注损伤）
Case PresentationA 50-year-old man was admitted to the hospital with severe chest pain of 5 hours duration. Mental confusion and in acute dyspnea （呼吸困难）. HR: 110 beats/min, sinus rhythm;BP: 75/50 mmHg;ECG: ST segment elevation, V1-V6LVEF: 31% X-ray: gross pulmonary edemaImprovement in breathBP: 100/70 mmHgLVEF: 38%Temporary ventricular tachycardia （心律不齐）diuretic, tissue plasminogen activatorBalloon angioplastyQuestion: why tachycardia occurred after operation?
Ischemic Injury is enhanced during reperfusion Reperfusion InjuryOxygen paradox, calcium paradox, pH paradox
Ischemia Components
0 hrReperfusionIschemic Injury of Neurons1 hr2 hr
IschemiaTimeInjuryDeathInjury WindowsReperfusionReperfusion injuryRecover
Early reperfusionDelayed reperfusionPersistent perfusion deficit 6 hr24 hr
Causes and Conditions of Reperfusion InjuryCausesConditionsRecover from cardiac arrestOrgan transplantationLysing thrombiIschemia timeBranch circulationOxygen consumptionTemperature, Na+, pH, Ca2+
Mechanisms of Reperfusion InjuryFree radicals↑Ca2+i↑Others
Free radicalAny atom or molecule possessing unpaired electronsSuperoxide anion (O2.-)Hydroxyl radical (OH.)Nitric oxide (NO.)Peroxynitrite （ONOO- )( 过氧亚硝酸盐）ˉLipid peroxide radical (LOO.)ˉOxygen free radicalsReactive oxygen species (ROS) Oxygen free radicalsHydrogen peroxide Others
1. Mitochondria2. Activated inflammatory cells3. Nitric oxide4. Ionizing radiationFormation of ROS
Reperfusion↑ Ca2+iROSMechanism 1
↑ Xanthine oxideseReperfusionIschemiaATP↑Ca2+iXanthine dehydrogenase↑HypoxanthinexanthineO2↓Uric acid↑ AMPO2O2.- H2O2Endothelial cellMechanism 2
IschemiaReperfusionO2Pro-inflammatory mediators(e.g. cytokines)NOONOO-O2.- (Respiration burst)Mechanism 3
Biochemical Impacts of ROS
Calcium OverloadThe abnormal increase of intracellular calcium which causes cell injury
Mechanism 1ReperfusionIschemia↓ ATP Membrane depolarizationCa2+↑Na+Na/Ca exchanger
↑ Ca2+Na+
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