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


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 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.


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.
Mori
E
E
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif. 92037.
del Zoppo
G J
GJ
Chambers
J D
JD
Copeland
B R
BR
Arfors
K E
KE
D000818:Animals; D000911:Antibodies, Monoclonal; D002545:Brain Ischemia / Q000503:physiopathology*; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation / Q000502:physiology*; D008833:Microcirculation; D009420:Nervous System / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D010215:Papio; D015424:Reperfusion; D014654:Vascular Patency
D000911:Antibodies, Monoclonal