Tissue factor contributes to microvascular defects after focal cerebral ischemia.
OBJECTIVE
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.
Thomas
W S
WS
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, Scripps Research Institute, La Jolla, Calif 92037.
Mori
E
E
Copeland
B R
BR
Yu
J Q
JQ
Morrissey
J H
JH
del Zoppo
G J
GJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology*; D010215:Papio; D015427:Reperfusion Injury / Q000503:physiopathology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology*
D000911:Antibodies, Monoclonal; D013925:Thromboplastin