Stroke, Vol 24, 847-853, Copyright © 1993 by American Heart Association
WS Thomas, E Mori, BR Copeland, JQ Yu, JH Morrissey and GJ del Zoppo
BACKGROUND AND PURPOSE: Microvascular perfusion defects occur after
occlusion and reperfusion of the middle cerebral artery in examples of
focal cerebral ischemia. In addition to cellular (eg, polymorphonuclear
leukocyte) contributors to the focal "no-reflow" phenomenon, activation of
coagulation may also play a role. We have tested a potential role of tissue
factor-mediated coagulation in the microvascular perfusion defects seen
after focal cerebral ischemia-reperfusion in a baboon model of reversible
middle cerebral artery occlusion with the murine anti-tissue factor
monoclonal antibody TF9-6B4. Tissue factor is the principal resident
procoagulant substance in cerebral tissues and has a distinct perivascular
distribution. METHODS: Microvascular patency in the basal ganglia after
3-hour middle cerebral artery occlusion and 1- hour reperfusion was
quantified by computerized video imaging of carbon- tracer perfused
tissues. Animals were randomized to receive intravenous TF9-6B4 (10 mg/kg)
10 minutes before middle cerebral artery occlusion (n = 6) or no treatment
(n = 6) in an open study. RESULTS: In the control animals, a significant
decrease in patency was confirmed in microvessels less than 30 microns in
diameter. Infusion of TF9-6B4 before middle cerebral artery occlusion
produced a stable maximal level of circulating antibody within 10 minutes,
which lasted the duration of ischemia and reperfusion. An increase in
reflow in microvessels of all size classes occurred after TF9-6B4 infusion,
which was significant in those 7.5 to 30 microns (P = .038) and 30 to 50
microns (P = .013) in diameter. CONCLUSIONS: These results indicate that
tissue factor- mediated events may also contribute to no-reflow in
noncapillary microvessels after focal cerebral ischemia.
ARTICLES
Tissue factor contributes to microvascular defects after focal cerebral ischemia
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, Scripps Research Institute, La Jolla, Calif 92037.
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