Stroke, Vol 23, 712-718, Copyright © 1992 by American Heart Association
E Mori, GJ del Zoppo, JD Chambers, BR Copeland and KE Arfors
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-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.
ARTICLES
Inhibition of polymorphonuclear leukocyte adherence suppresses no- reflow after focal cerebral ischemia in baboons
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif. 92037.
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