1 / 42

Ischemia-reperfusion injury (IRI)

Ischemia-reperfusion injury (IRI). Introduction 1955, Sewel tied up coronary of dog ， loose suddenly ventricular fibrillation 。 Kane tied up left entricular branch of coronary of rat ECG no obvious change

hiroko
Télécharger la présentation

Ischemia-reperfusion injury (IRI)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ischemia-reperfusion injury (IRI)

  2. Introduction 1955, Sewel tied up coronary of dog， loose suddenly ventricular fibrillation。 Kane tied up left entricular branch of coronary of rat ECG no obvious change relieve deligation arrhythmic

  3. 1972 Flore kidney IRI 1978 Modry lung IRI 1981 Greenberg intestine IRI

  4. Concept: based on ischemia injury of tissue and organs restoration of blood flow after transient or ischemia further reversible or irreversible cell damage ischemia reperfusion injury（IRI）。

  5. pH paradox ischemia acidosis , disorder of function and metbolism on cell severe IRI pH paradox calcium paradox pre-perfuse rat heart with no calcium perfusion for 2min perfuse calcium perfusion, cell release enzyme myofibril over-constract, electron signals abnormal， calcium paradox

  6. Oxygen paradox Hypoxia liquid perfuse organ or culture without oxygen injury restore perfusionsevere injury

  7. Ⅰ. Cause of ischemia-reperfusion injury and affecting factor coronary in spasm antispasmotic thrombosisthrombolytic therapy 1. causecoronaryby-pass operation on heart: no-reflow organ transplant

  8. 2．Affecting factor small 5-10min: arrhythmia ⑴ ischemic animals 20-30min: ventricular time tremor big 20-40min: reversible injury animals 40-60min: irreversible injury diversity between small and big animal

  9. Changes of ischemic perfuse: ATP、Ca2+、K+

  10. ⑵ collateral(侧枝) circulation：chronic ⑶ O2 consumption rate [K+ ] , [Mg2+] protection ⑷ electrolytes [Na+ ] , [Ca2+] damage (5) condition of T, pressure,pH,Na+,Ca2+protection reperfusion T, pressure,Na+,Ca2+damage

  11. Ⅱ. pathogenesis of ischemia-reperfusion injury 1. The role of free radical ⑴ kinds and concept of free radical free radical:

  12. normal: O2 +4e+4H+ 2H2O O2 →O-•2 H2O2 OH • H2O e- +2H + e- +H + e- +H + e- H2O

  13. oxygen free radical: O-•2 、OH • kinds of (active oxygen: 1O2、H2O2 OH •) free radical lipid free radical: L•、LO•、LOO• others: Cl•、CH3•、NO

  14. (2) mechanism of increase of oxygen free radical  ① formation of oxygen free radical nature oxidation of Hb , Cyt C O2 O ‾∙2 H2O2 OH∙ H2O H2O oxidation of enzyme : xanthine oxidase(XO) O ‾∙2 xanthine uric acid O2 O ‾∙2 Mitochondria: O ‾∙2

  15. normal: O2+4e+4H+→H2O+ATP abnormal :O2+e→O·-2+e +2H+→H202+e+H+→ OH·+e+H+→H20 Cyt P450Oinsert C—H C—OH O +2H + H2O O ‾∙2 H2O2

  16. Produce of OH·SOD O·-2+ O·-2+2H+ H2O2+O2 O·-2+H2O2 OH· + OH·+O2 Fenton Haber-Weiss： SOD Fe2+ Fe3+ O·-2 H2O2 OH·+ OH-

  17. （2） lipid free radicalconcept： types：L· , LO· LOO· （3）non- lipid free radical: NO·、 ONOO- They are balance between produce and clearance

  18. Haber-Weiss reaction(Fenton reaction ) OH ∙ Fe3+ + O‾∙2 Fe2+ + O2 H2O2 Fe3+ + OH-+ OH∙   O ‾∙2 + H2O2 Fe盐O2 + OH-+ OH∙ O‾∙2 + OH∙1O2 + OH- CI+ + H2O H2O+OCl- 1O2 OCl- + H2O2 1O2 + Cl-+ H2O photosensitive substance O2 1O2 effects:WBC

  19. 2O‾∙2 + 2H +SOD H2O2+ O2 H2O2 O2 Other oxidase 2H+ H2O2 application disinfection

  20. ② increase of oxygen free XD Xanthine oxidase (XO) : Ischemia ATP [Ca2+]i xanthine xanthine dehydrogenase oxidase

  21. Xanthine oxidase pathway ATP ADP AMP Adenine nucleoside Ca2+ Hypoxanthine nucleoside Hypoxanthine xanthine+O‾∙2+H2O O2 Uricacid +O‾∙2+H2O Fe 2+ OH∙ ischemia XD xo reperfusion XO

  22. The effects of leucocyte reperfusion：oxygen consumption of infiltrated WBC ↑70-90% O2 NADPH +2O2 2O·-2+NADP++H+ NADH+O2+2H+ H2O2+NAD+ +H+ NADPH氧化酶 NADH氧化酶

  23. Phenomenon of increase in production of oxygen radicals 1.repiratory burst O‾∙2 \ OH∙ (oxygen burst) 2.hypoxia mitochondria repiratorychain O‾∙2 Ca2+

  24. (3) damage action of free radical ① membrane lipid peroxidation cellular membrane permeability lipid peroxidation of membrane [Ca2+] i calcium overload

  25. lipid cross-linked calcium overload inhibition of Na+-pump and Ca2+-pump [Na+] i , [Ca2+] i membrane lipid phospholipase C PGs , LTs（花） peroxidation phospholipase D TXA2 damage of mitochondria membrane ATP

  26. ② inhibition of protein function enzymes ：stop heart beat IR GSH(blood)injury ofprotein channels: ③ destruction of nuclear acid DNA- DNA, DNA-protein :

  27. (1) mechanism of calcium overload   Ca2+ input ① abnormal exchange of Na+/Ca2+ ATP Na+-pump [Na+] i exchange of Na+(out)/Ca2+ (in) (convert) hypoxia exchange acidosis of Na+(in)/H+(out) [Na+] i normal exchange of Na+(in)/Ca2+(out) ，

  28. NE α1 PI（磷脂） ischemia catecholamine α1 – receptor H+ Ca2+ Na+ Ca2+ IP3 and DG PKC Ca2+ Normal:βreceptor Gq PLC S R Ca2+

  29. NE Cellular membrane β catecholamine β– receptor [Ca2+] i L Ca2+- channel Ca2+ pre-apply anti-Ca2+ drugs GOOD ② injury of biomembrane damage of cellular membrane normal glycocalyx Ca2+ bridge Cellular membrane Cellular membrane

  30. Cellular membrane No Ca2+ glycocalyx reperfusion Ca2+ glycocalyx Ca2+ lipid break up PLA2 Cellular membrane

  31. Damage of mitochondria and sarcoplasmic Damage of mitochondria ATP Damage of Sarcopasmic Ca2+- ATPase calcium overload

  32. (2) Damage mechanism of calcium overload ①phospholipase injury of cell membrane and cell organ  ②output of Ca2+ consumption of ATP ③Ca2+ + phosphate production of ATP deposition ④ [Ca2+] i XO free radical ⑤ [Ca2+] i

  33. 3. role of leukocyte In 1984，Mullane found that conorary was obstructed 60min， Engler， Ischemia phospholipase LTs Congregate of leukocyte Expression of adhesion molecule Release inflammatory factor Production of free radical no-reflow

  34. 5. Role of neutrophil : • Injury of microvessle microcirculation： caliber contracte , dialate permability 2) Injury of cells

  35. Ⅲ. Changes of function and metabolism 1. changes of heart in ischemia-reperfusion injury arrhythmia heart function cardiac output free radical energy calcium overload damage of mitochondria reperfusion sweep of ADP，AMP produce ATP myocardial destruction of membrane structural rupture and dissolve of myofibril damage damage of mitochondrion

  36. 2. changes of brain in ischemia-reperfusion injury ATP Na+-pump cellular edema Hypoxia of cells cellular acidosis Excitability transmitter inhibitive transmitter cAMP↑ cGMP↓ activate free fatty acid↑ lipid peroxidation↑

  37. Hisconstructure Edema , necrosis 3. Others Colone, kidney

  38. Ⅳ. Principles of prevention and treatment 1. restoring normal perfusion of tissue in time low temperature; low pressure; low flow; low natrium(sodium); low pH; low calcium

  39. 2. improve the metabolism of the tissues ATP; cytochrome C; 3. sweep away free radical: VitE: lose e FR FR (lipid) VitC: clear OH∙ (water) β-cartenoids: clear 1O2 GSH

  40. （2）enzymescavenger： 2 O‾∙2 +2H+ H2O+O2 H2O2H2O+O2 4. relieve of calcium overload Ca2+ ion blok agent SOD CAT

  41. 5. CoQ Inhibit L • (lipid free radical) 2L+ CoQ 2LH+ CoQ protein enzyme inhibitor: ulinastatin

More Related