Antithrombotic effect of recombinant calphobindin I (rCPB-I), which has indistinguishable biochemical and pharmacological properties from native CPB-I in vitro, was studied in vivo.
The lumen of the carotid artery was damaged by rubbing 20 strokes with 2F balloon catheter, and the injured region was stenosed by constrictor to induce the thrombus formation. rCPB-I iv infused 0.5 and 1.0mg/kg/hr showed dose-dependent suppression of the thrombus formation affecting neither APTT nor whole blood clotting time (r+k value of thromboelastogram). Heparin iv infused 100U/kg/hr also showed an antithrombotic effect as same as that caused by rCPB-I 1.0mg/kg/hr, however it revealed marked prolongation of both coagulating parameters.
To investigate the mechanism of the action of rCPB-I, the binding property of 125I labeled rCPB-I to the damaged vessel was examined in a rabbit carotid artery perfusion system, resulting that 6-fold much radioactivity was detected in the injured region than in the normal region under the condition of physiological Ca++ concentration.
These results suggest that rCPB-I could bind to some components in injured lumen of the carotid artery and suppress the initiation of solid phase blood coagulation.
