1.What is concept of IschemiaReperfusion Injury
2.Which factors can affect reperfusion injury? ischemic duration and severity reperfusion speed reperfusion fluid component ischemic preconditioning electrolytes
3.What is the mechanism of ischemia-reperfusion injury?
4.What is the mechanism of no-reflow phenomenon • Vaso-endothelial edema • Vaso-endothelial damage • Occlusion of microvascular lumen
No - Reflow Phenomenon
5.What is the role of leukocyte in IRI Swelling Adhesion Infiltration Release: arachidonic acid, PAF, lysosomal enzyme Respiratory burst Cell adhesion molecules(CAM): selectins, integrins, immunoglobulin superfamily
6.What leads to calcium overload in IRI?
Na+ - Ca2+ exchange↑ ATP ↓: mitochondria, precursor ↓ Membrane permeability ↑ catecholamine ↑
Na+ - Ca2+ exchange↑
7.What are the detrimental effects of Ca2+ overload to tissue? mitochondria damage activating phospholipase A2 activating Ca2+-activated protease Cellular electrical action: arrhythmia
8.How does OFR metabolism undergo in the body ?
OFR metabolism O2 + e Cytaa3
O2 •
O2+ 2e + 2H+
O2 + 3 e + 3H
H2O2 +
O2 + 4 e + 4H+
SO HO• + H2O D CAT
2 H2O
Single electron reduction of
Haber-Weiss reaction (without
－ • O2 + H 2O 2
SLOW
Fe
+3
)
O 2 + OH +OH•
Fenton type of HaberWeiss reaction( with ) Fe
Fe
O 2 • + H 2O 2 －
+3
+3
FAST
O 2 + OH +OH•
9.Why does OFR increase in IRI? • • • •
Endothelium: XO↑↓ Neutrophil: respiratory burst Mitochondrium: MnSOD ↓, Ca2+ ↑ Catecholamine↑:
ischemia: ATP degradation Hypoxathine↑↑
(1)Ca reperfusi
2+
→protease
O2
on: XD
XO
（ 2 ） restore O2
XO role in formation of OFR
xanthine + O·-2+ H2O2
O2 O·-2+ H2O2 +uric acid
OH ·
Neutrophil: C3,LTB4
respiratory burst
Activating NP respiratory burst NADH oxidase
NADH(I) •+ H + O ·+H O 2 2 2 NADPH(II)+ O2 NADPH oxidase
Mitochondrium Ca2+ ↑ enter Mitochondrium
hypoxia→MnSOD ↓
Single electron reduction of O2↑ -
■O·
↑
2
Catecholamine autooxidation↑ Adr
Methyle transferase Monoamine oxidase
Vanillylmandelic acid （ nor met ）
80% of O2 during stress
O-2·↑
Adrenochrome redness
Removed by kidney
10.What are the detrimental effects of OFR to tissue? lipid membrane protein: channel, pump, enzyme nuclear acid : DNA
Pro
cross linkage Disulfide cross linkage
Lipidpro cross linkage
Pro split -S-S-
OH HO
CH3-SO2 Aminoac id oxidatio n
OH HO
Lipid-lipid cross linkage
Fat acid oxidation
MDA (malondialdihyd e)
11.How prevent and treat IRI (1) Restore normal perfusion of tissue in time (2) Pharmacologic agents Ca2+ antagonist, Ca2+ channel blocker OFR scavenging agents glutathione peroxidase(GP) GSH + H2O2
GSSG + H2O
GP