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

• Published in: Stroke (1970) Vol. 23; no. 5; pp. 712 - 718
• Main Authors: MORI, E, DEL ZOPPO, G. J, CHAMBERS, J. D, COPELAND, B. R, ARFORS, K. E
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-05-1992
• Subjects: Animals; Antibodies, Monoclonal; Biological and medical sciences; Brain Ischemia - physiopathology; Cell Adhesion; Cerebrovascular Circulation - physiology; Medical sciences; Microcirculation; Nervous System - physiopathology; Nervous system involvement in other diseases. Miscellaneous; Neurology; Neutrophils - physiology; Papio; Reperfusion; Vascular Patency; Nervous system diseases; Leukocyte; Granulocyte; Monkey; Exploration; Adhesion; Endothelium; Microcirculation; Vertebrata; Experimental disease; Mammalia; Ischemia; Animal; Primates; Inhibition; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.STR.23.5.712

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-CD18 monoclonal antibody IB4, which inhibits neutrophil adherence to endothelium.
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.
In the untreated group, a significant reduction in patency was observed in microvessels less than 30 microns diameter: mean percent reflow was 51% in the capillary diameter class (4.0-7.5 microns) and 39% in the precapillary arteriole and postcapillary venule diameter class (7.5-30 microns). Infusion of IB4 before middle cerebral artery reperfusion increased reflow in microvessels of all size classes, most significantly in those 7.5-30 microns (p = 0.049) and 30-50 microns (p = 0.034) in diameter.
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.