Reactive oxygen metabolites, neutrophils, and the pathogenesis of ischemic-tissue/reperfusion

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Abstract
Considerable research effort has been directed at elucidating the mechanisms underlying the pathophysiologic alterations associated with reperfusion (reoxygenation) of ischemic (hypoxic) tissues. As a consequence of this intensive effort, a large body of evidence has accumulated, implicating a role for reactive oxygen metabolites and activated granulocytes in the genesis of postischemic cellular dysfunction. Figure 1 summarizes a hypothesis that has been proposed to explain the interaction of xanthine oxidase‐derived oxidants, granulocyte infiltration, and the microvascular and parenchymal cell dysfunction that occurs in postischemic tissues.1–4 According to this scheme, xanthine oxidase‐derived oxidants, produced at reperfusion, initiate the formation and release of proinflammatory agents, which subsequendy attract and activate granulocytes. The activated neutrophils adhere to the microvascular endothelium, extravasate, and release cytotoxic oxidants and proteases, which contribute to tissue dysfunction. The aim of this review is to summarize the evidence that we and others have accumulated in support of this hypothesis.