PHYSIOLOGIC MECHANISMS OF POSTISCHEMIC TISSUE INJURY

Early restitution of blood flow to ischemic tissues is essential to halt the progression of cellular injury associated with decreased oxygen and nutrient delivery. Recognition of this fact provides the basis for the traditional view that minimizing ischemic time is the only important intervention for diminish­ ing the extent of ischemic injury. However. it is now clear that reperfusion of ischemic tissues initiates a complex series of reactions that paradoxically injures tissues. Although several mechanisms have been proposed to explain the pathogenesis of ischemialreperfusion (IIR) injury. most attention has fo­ cused on a role for reactive oxygen metabolites and inflammatory leukocytes. This work has led to the proposal that' free radical ablation or inhibition of postischemic neutrophil infiltration may prove useful for therapeutic interven­ tion in I1R. In addition to these mechanisms. recent evidence suggests that prior exposure to brief periods of ischemia (ischemic preconditioning) prevents the development of cellular injury induced by a subsequent prolonged inter­ ruption in blood flow. By elucidating the cellular events underlying precondi­ tioning. additional mechanisms contributing to the pathogenesis of I/R may become apparent. This review summarizes the evidence supporting the view that oxidants and leukocytes contribute to the pathogenesis of reperfusion injury and discusses the mechanisms underlying the protective actions of ischemic preconditioning.