Abstract:

Ischaemia and reperfusion injury is a potentially serious problem that is encountered during a variety of medical and surgical procedures, such as thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. The basic pathophysiology of ischaemia and reperfusion injury is microvascular dysfunction which is developed following reperfusion of ischaemic tissues. This phenomenon is manifested as impaired endothelium-dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and the trafficking of leukocytes and plasma protein extravasation in postcapillary venules. Activated endothelial cells in the microcirculation produce more oxygen radicals, but less nitric oxide, in the initial period following reperfusion. The resulting imbalance between superoxide and nitric oxide in endothelial cells leads to the production and release of inflammatory mediators (e.g. platelet-activating factor, tumour necrosis factor) and enhances the biosynthesis of adhesion molecules that mediate leukocyte-endothelial cell adhesion. The inflammatory 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. This distant response to ischaemia and reperfusion can result in leukocyte-dependent microvascular injury that is characteristic of the multiple organ dysfunction syndrome.

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