Ischemia Reperfusion Injury
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Transcript of Ischemia Reperfusion Injury
Heider SH. AL-Qassam
MSc.PH. &TH.
Ischemia(inadequate
oxygen supply)
Reperfusion
inflammatory responses
local injury &
impairmentof organ function
stroke
MI
organ transplantation
cardiopulmonary bypass
ATP depletion
Defective ATP-resynthesis
Increase in hypoxanthine
Activation of xanthine oxidase
Molecular effects
Antioxidant (glutathione) depletionIntracellular Na+ and Ca++-overloadActivation of NHEActivation of PLA2Activation of NFkβ
Endothelial cell dysfunction/swelling
Leukocyte (PMN) recruitment
Impaired vasodilatation (NO-mediated)
Enhanced vasoconstriction(endothelin-
mediated)
Endothelial barrier disruption
Expression of adhesion molecules
Cellular effects
Mitochondrial dysfunction/swelling
Translocation of bax
Efflux of cytochrome c
Lipid peroxidation
Cell membrane damage
Increased cell membrane permeability
Cytoskeletal derangements
Subcellular effects
Arachidonic acid metabolites (LTB4,
TXA2)
Cytokines (IL-1b, IL-6, TNF-a)
Chemokines (IL-8, MCP-1)
Activated complement (C3a, C5a, C5b-
9)
Mediators
Anti-inflammatoryI.Inhibition of leukocyte accumulationII.Complement inhibition (pexelizumab)Inhibition of mPTP ( ex: cyclosporine)Prevention of intracellular calcium overloadReducing ROS by Inhibition of xanthine oxidase
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