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1、ischemia-reperfusion injury pathophysiology department, tongji medical college, hust concepts: ischemia-reperfusion (i-r) injury, oxygen/calcium/ph paradox, calcium overload, no-flow phenomenon causes and conditions of i-r injury mechanisms of i-r injury metabolic and functional alterations preventi

2、on and treatment principlecontentsaggravated ischemic injury during reperfusion reperfusion injuryischemia components0 hrreperfusionischemic injury of neurons1 hr2 hrischemiatimeinjurydeathinjury windowsreperfusionoxygen paradox, calcium paradox, ph paradoxcauses and conditions of reperfusion injury

3、causesconditionsrecover from cardiac arrestorgan transplantationlysing thrombiischemia timebranch circulationoxygen consumptiontemperature, na+, ph, ca2+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.

4、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?mechanisms of reperfusion injuryfree radicalsca2+ineutrophil activation and

5、 othersfree radicalany atom or molecule possessing unpaired electronssuperoxide anion (o2.-)hydroxyl radical (oh.)nitric oxide (no.)peroxynitrite (onoo- )( 过氧亚硝酸盐)lipid peroxide radical (loo.)oxygen free radicalsreactive oxygen species (ros) oxygen free radicalshydrogen peroxide others1. mitochondri

6、a2. activated inflammatory cells3. nitric oxide4. ionizing radiationformation of rosreperfusion ca2+irosmechanism 1o2 xanthine oxidesereperfusionischemiaatpca2+ixanthine dehydrogenasehypoxanthinexanthineo2uric acid ampo2o2.- h2o2endothelial cellmechanism 2ischemiareperfusiono2pro-inflammatory mediat

7、ors(e.g. cytokines)noonoo-o2- (respiration burst)mechanism 3biochemical impacts of roscalcium overloadthe abnormal increase of intracellular calcium which causes cell injury mechanism 1reperfusionischemia atp membrane depolarizationca2+na+na/ca exchanger ca2+na+reperfusionh+h+ na+ischemiaca2+na+mech

8、anism 2h+na/h exchangerreperfusionca2+na+h+na+a1naplcpidgpkcip3srca2+mechanism 3mechanism 4reperfusionmitochondriaersrca2+na+i gene activation neutrophil activation neutrophil activation and othersneutrophil activation rosinflammatorymediatorsinjury of micro-vessels no-reflow phenomenoncell injuryro

9、le of neutrophilreperfusion structural and functional changes reperfusion arrhythmiamyocardial stunningheart:brain:edemacell deathelectrocardiographic alterations associated with the three zones of myocardial infarctionheart injuryischemia-reperfusion injurycalcium overload free radical destroy of contractile protein myocardial stunningca+ k+ na+arrhythmiacell deathbrain injuryprinciples of prevention and treatment control of reperfusion conditionsremova

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