TISSUE FACTOR CONTRIBUTES TO MICROVASCULAR DEFECTS AFTER FOCAL CEREBRAL-ISCHEMIA

Background and Purpose: Microvascular perfusion defects occur after oc clusion and reperfusion of the middle cerebral artery in examples of f ocal cerebral ischemia. In addition to cellular (eg, polymorphonuclear leukocyte) contributors to the focal ''no-reflow'' phenomenon, activa tion of coagulation may also play a role. We have tested a potential r ole of tissue factor-mediated coagulation in the microvascular perfusi on defects seen after focal cerebral ischemia-reperfusion in a baboon model of reversible middle cerebral artery occlusion with the murine a nti-tissue factor monoclonal antibody TF9-6B4. Tissue factor is the pr incipal 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 carbo n-tracer perfused tissues. Animals were randomized to receive intraven ous TF9-6B4 (10 mg/kg) 10 minutes before middle cerebral artery occlus ion (n=6) or no treatment (n=6) in an open study. Results: In the cont rol animals, a significant decrease in patency was confirmed in microv essels less than 30 mum in diameter. Infusion of TF9-6B4 before middle cerebral artery occlusion produced a stable maximal level of circulat ing antibody within 10 minutes, which lasted the duration of ischemia and reperfusion. An increase in reflow in microvessels of all size cla sses occurred after TF9-6B4 infusion, which was significant in those 7 .5 to 30 mum (P=.038) and 30 to 50 mum (P=.013) in diameter. Conclusio ns: These results indicate that tissue factor-mediated events may also contribute to no-reflow in noncapillary microvessels after focal cere bral ischemia.