PRETREATMENT OF RABBITS WITH EITHER HIRUDIN, ANCROD, OR WARFARIN SIGNIFICANTLY REDUCES THE IMMEDIATE UPTAKE OF FIBRINOGEN AND PLATELETS BY THE DEENDOTHELIALIZED AORTA WALL AFTER BALLOON-CATHETER INJURY IN-VIVO

Fibrinogen and platelets rapidly saturate the exposed subendothelium o f a freshly deendothelialized aorta in vivo. As thrombin generated wit hin the site of injury is largely responsible for fibrin(ogen) deposit ion, we questioned whether various anticoagulant treatments would inhi bit uptake of both fibrinogen and platelets in vivo. Rabbits were anti coagulated by pretreatment with either Warfarin, Ancrod, or recombinan t hirudin, Each anesthetized, anticoagulated (or saline-injected contr ol) rabbit was injected IV with rabbit Cr-51-platelets and I-125-fibri nogen before a balloon-catheter deendothelializing (or sham) injury of the thoracic aorta. At 10 minutes after injury, the rabbit was exsang uinated and the aorta excised, Platelet adsorption by the deendothelia lized aorta surface was substantially reduced in anticoagulated rabbit s (controls, 2.2X10(5)/mm(2); Warfarin-treated, 1.2X10(5)/mm(2); Ancro d-treated, 5.3X10(4)/mm(2); r-hirudin-treated [5 mg/kg], 5.3X10(4)/mm( 2)), and a significant reduction of fibrinogen associated with the pla telet layer (from 5.3 to 1 to 2 pmol/cm(2)) and within the underlying intima-media layer (from 16.9 to 5 to 6 pmol/cm(2)) was observed in th e r-hirudin-and Warfarin-treated rabbits. The pattern of aorta-deposit ed Cr-51-platelets and I-125-fibrin in the anticoagulated rabbits corr esponded well with an assessment by transmission electron microscopy o f aortic tissue samples. We conclude that approximate to 70% of fibrin ogen uptake is thrombin dependent and that approximate to 80% of plate let adsorption depends on codeposited fibrin(ogen) during the 10-minut e interval after balloon injury. Pretreatment with an agent that inter feres with either thrombin or fibrin production will inhibit the immed iate interaction of fibrinogen and platelets with the freshly exposed subendothelium.