Polymorphonuclear Leukocyte Adherence and Microvascular Reflow After Focal Cerebral Ischemia/Reperfusion

Abstract

Interruption of normal cerebral arterial blood flow by atherothromboemboli or thrombi in situ in a territory unprotected by adequate collaterals may lead to neuronal necrosis and tissue disruption (Ziilch 1985). Reperfusion of the occluded artery, as may occur following successful use of thrombolytic agents within hours of flow interruption (del Zoppo et al. 1988, 1992; Mori et al. 1988, 1992a,b), introduces significant additional vascular events. Particularly vulnerable is the distally (downstream) dependent microvascular bed which receives the full force of arterial reperfusion. In models of global cerebral ischemia, microvascular perfusion defects (“no-reflow”) have been demonstrated following reperfusion (Ames et al. 1968). Similar postreperfusion obstructions to reflow in the microvascular bed, manifest by loss of patency, have been described in the setting of experimental cardiac and skeletal muscle ischemia (Kloner et al. 1974; Engler et al. 1987; Schmid-Schonbein 1987). It has been postulated that such microvascular perfusion defects may result from perivascular edema or hemorrhage, endothelial cell edema, endothelial cell tags, in situ thrombosis, erythrocyte aggregation, platelet adherence and aggregation, polymorphonuclear (PMN) leukocyteendothelial cell adherence, rheologic properties of PMN leukocytes, and other mechanisms. The appearance of “no-reflow” following single artery occlusion and subsequent reperfusion (O/R), as might occur in focal cerebral ischemia, has been suspected, but only recently described (del Zoppo et al. 1991).