Reperfusion injury: Experimental evidence and clinical implications

Abstract

Postischemic reperfusion may profoundly alter cardiac function. Principal mediators of this phenomenon are oxygen radicals and neutrophils. Upon reflow, oxygen radicals are generated in large amounts, overwhelming cellular defenses and inducing oxidative tissue damage; biochemical markers of oxygen radical formation and attack can be found in postischemic myocardium. Reintroduction of neutrophils in postischemic tissues is accompanied by their activation, with release of lytic enzymes that directly induce tissue damage and proinflammatory mediators that amplify the local inflammatory reaction. Neutrophils may also plug capillaries, mechanically blocking flow. Oxidants can also modulate various events, ultimately leading to tissue injury, such as nitric oxide formation, platelet-activating factor metabolism, tissue factor synthesis, and exposure of adhesion molecules. In the clinical setting, important consequences of postischemic reperfusion are reversible contractile dysfunction (“stunning”), which is mostly caused by oxygen radical attack, and impairment to flow at the microvascular level (“no-reflow”) secondary to neutrophil plugging and vasoconstriction. (Am Heart J 1999;138:S69-S75.)