Related Experiment Videos
Tissue factor contributes to microvascular defects after focal cerebral ischemia
W S Thomas1, E Mori, B R Copeland
1Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, Scripps Research Institute, La Jolla, Calif 92037.
Stroke
|June 1, 1993
Summary
Blocking tissue factor with TF9-6B4 antibody improved blood flow in microvessels after focal cerebral ischemia and reperfusion. This suggests tissue factor plays a role in the no-reflow phenomenon in noncapillary vessels.
Area of Science:
- Neuroscience
- Vascular Biology
- Coagulation Research
Background:
- Focal cerebral ischemia leads to microvascular perfusion defects, known as the no-reflow phenomenon.
- Cellular factors and coagulation activation contribute to no-reflow.
- Tissue factor, a procoagulant, is present in cerebral tissues with a perivascular distribution.
Purpose of the Study:
- To investigate the role of tissue factor-mediated coagulation in microvascular perfusion defects after focal cerebral ischemia-reperfusion.
- To evaluate the efficacy of a murine anti-tissue factor monoclonal antibody (TF9-6B4) in a baboon model.
Main Methods:
- Reversible middle cerebral artery occlusion for 3 hours followed by 1 hour of reperfusion in baboons.
- Quantification of microvascular patency using computerized video imaging of carbon-tracer perfused tissues.
- Randomization to intravenous TF9-6B4 (10 mg/kg) before occlusion or no treatment.
Main Results:
- Control animals showed decreased patency in microvessels <30 microns.
- TF9-6B4 infusion achieved stable antibody levels and significantly increased reflow in microvessels sized 7.5-30 microns (P=.038) and 30-50 microns (P=.013).
- Improved reflow was observed across all microvessel size classes.
Conclusions:
- Tissue factor-mediated coagulation contributes to the no-reflow phenomenon in noncapillary microvessels after focal cerebral ischemia.
- Targeting tissue factor may be a therapeutic strategy to improve microvascular perfusion in ischemic stroke.