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 infl ammatory mediators (e.g., platelet-activating factor, tumour necrosis factor) and upregulate the expression of adhesion molecules that promote leukocyteendothelial cell adhesion. Once leukocytes reach the extravascular space, they exacerbate tissue injury by releasing oxygen free radicals and other destructive enzymes. Th 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. Th e protein kinases initiate several interconnected intracellular enzyme reactions. Th e infl 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. Th is distant response to HR can result in severe generalized infl ammatory response and can result in multiple organ dysfunction syndrome.
