Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons

Abstract

Background and Purpose: While polymorphonuclear leukocytes may contribute to the “no-reflow” phenomenon after focal cardiac and skeletal muscle ischemia/reperfusion, their contribution to acute focal cerebral ischemia is unresolved. We have examined the role of polymorphonuclear leukocytes in microvascular perfusion defects after focal cerebral ischemia/reperfusion in a baboon model of reversible middle cerebral artery occlusion with the anti-CD 18 monoclonal antibody IB4, which inhibits neutrophil adherence to endothelium. Methods: Microvascular patency in the basal ganglia after 3-hour middle cerebral artery occlusion and 1-hour reperfusion (by india ink tracer perfusion) was quantified by computerized video imaging. Animals were randomized to receive intravenous IB4 infusion 15 minutes before reperfusion (n=7) or to receive no treatment (n=6). Binding of IB4 to baboon leukocytes was maximal within 5 minutes of infusion. Results: In the untreated group, a significant reduction in patency was observed in mlcrovessels <30μm diameter mean percent reflow was 51% in the capillary diameter class (4.0-7.5 μm) and 39% in the precapillary arteriole and postcapillary venule diameter class (7.5-30μm). Infusion of IB4 before middle cerebral artery reperfusion increased reflow in microvessels of all size classes, most significantly in those 7.5-30 μm (p=0.049) and 30-50 pm (p=0.034) in diameter. Conclusions: These results suggest that CD18-mediated polymorphonuclear leukocyte-endothelium adherence contributes to no-reflow predominantly in noncapillary microvessels and at least partially to that in capillaries. © 1992 American Heart Association, Inc.