Vascular dysfunction in ischemia-reperfusion injury

Microvascular dysfunction mediates many of the local and systemic consequences of ischemic-reperfusion (I/R) injury, with a spectrum of changes specific to arterioles, capillaries, and venules. This review discusses the specific changes in the endothelium during I/R injury; describes the differential responses of the various levels of the vasculature including arterioles, capillaries, and venules; and explores mechanisms for remote organ injury. Vascular dysfunction is largely a consequence of changes in the endothelial cells themselves, affecting the integrity of barrier function, cytokine and adhesion molecule expression, and vascular tone. The bioavailability of nitric oxide, an important mediator of vasodilation, is profoundly decreased during the reperfusion period, resulting in impaired vasodilation of arterioles. Release of inflammatory mediators and increased expression of adhesion molecules initiate inflammatory and coagulation cascades that culminate in the occlusion of capillaries, known as the no-reflow'' phenomenon. In postcapillary venules, the recruitment and transmigration of leukocytes further compromise the integrity of the endothelial barrier and increase the oxidative burden, resulting in leakage and tissue edema. I/R injury can have significant and untoward consequences beyond the affected tissue, with such conditions as systemic inflammatory response syndrome. This review highlights recent progress in understanding of the varied phenomena of vascular dysfunction in I/R injury and some promising advances in the understanding and application of ischemic preconditioning and other potential therapies.