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

Thank you