Biomedical Engineering Reference
In-Depth Information
15
CHAPTER
Hypoxia Reperfusion Injury and
Adhesion Molecules
Kamran Ghori
Consultant Anaesthetist, Department of Anaesthesia, Bon SECOURS Hospital,
College Rd. Cork, Republic of Ireland, E-mail:
kamrang@hotmail.com
ABSTRACT
Hypoxia reperfusion (HR) injury has been recognized to play a key role in the
pathogenesis of many kinds of organ dysfunction. Ischaemia occurs in various
clinical conditions such as myocardial infarction, stroke, peripheral vascular
disease and hypovolumeic shock. It is important to restore the blood supply of the
ischaemic organ, but sometimes reperfusion itself can cause tissue injury in excess
of that caused by ischaemia alone. Reperfusion of ischaemic tissues is associated
with microvascular dysfunction, manifested by enhanced leukocyte plugging
in capillaries, and the migration of leukocytes into intrestisuum. Activated
endothelial cells and leukocytes in all segments lead to the production and release
of inl ammatory mediators (e.g., platelet-activating factor, tumour necrosis factor)
and upregulate the expression of adhesion molecules that promote leukocyte-
endothelial cell adhesion. Once leukocytes reach the extravascular space, they
exacerbate tissue injury by releasing oxygen free radicals and other destructive
enzymes. h e production of adhesion molecules in endothelium and leukocytes is
regulated by a family of protein kinases, which are important signalling pathways
during HR injury. h e protein kinases initiate several interconnected intracellular
enzyme reactions. h e inl ammatory mediators released as a consequence of
reperfusion also appear to activate endothelial cells in remote organs that are not
exposed to the initial ischaemic insult. h is distant response to HR can result
in severe generalized inl ammatory response and can result in multiple organ
dysfunction syndrome.
