GUINEA-PIG BLOOD - A MODEL FOR THE PHARMACOLOGICAL MODULATION OF THE GPIB IX-VWF AXIS/

Antithrombotic activity of two recombinant GPIb-binding fragments of v WF, RG12986 (residues 445-733), and VCL (residues 504-728), were asses sed in an ex vivo capillary perfusion chamber exposing human type III collagen to native nonanticoagulated guinea pig blood. Platelet adhesi on and thrombus formation were evaluated by computer assisted morphome try for two shear rates (650 and 1800 s(-1)) and for two perfusion tim es (1.5 and 4 min). At 1800 s(-1) and 4 min of perfusion, platelet adh esion decreased from 63 +/- 7% for control, to 46 +/- 4% for 20 mg/kg RG12986, and to 29 +/- 5% for 4 mg/kg VCL, and the mean thrombus heigh t dropped from 40 +/- 8 mu m to 24 +/- 3 mu m and 7.5 +/- 1 mu m, resp ectively. The two doses did not change bleeding time values. Our resul ts suggest that guinea pig blood and the circular perfusion chamber re present a good model for the evaluation of limited amount of GPIb/IX-v WF axis Inhibitors.