The metabolic characteristics of two rabbit plasma thrombin inhibitors, heparin cofactor II (HCII) and antithrombin (AT), have been compared in healthy young rabbits. Purified HCII and AT-alpha were differentially radiolabeled (125I, 131I) and injected intravenously; blood samples were taken at prescribed intervals over 7 days. From the plasma clearance curves of protein-bound radioactivities, fractional catabolic rates and compartmental distributions were calculated using a three-compartment model. The whole body fractional catabolic rate for HCII (jt, 0.43/day, equivalent to t1/2 = 1.61 days) was significantly faster than for AT (jt, 0.37/day; t1/2 = 1.89 days; P < 0.005). The fractional distribution of HCII in the intravascular compartment (Ap, 0.20) and in the extravascular compartment (Ac, 0.63) differed significantly from AT (Ap, 0.30; Ac, 0.56). From the catabolic data and blood concentrations, absolute quantities of HCII and AT catabolized by a 3-kg rabbit amounted to 12.8 and 19.9 mg/day, respectively, equivalent to a molar ratio, AT/HCII, of 1.7. The catabolic molar ratio was compared with the relative release rates of HCII and AT from perfused rabbit livers. Both proteins were released from the liver, the molar ratio in the perfusate rising to approximately 1.4 at 2.5 h. This report increases our understanding of the in vivo dynamics of these two proteins.

Abstract-Fibrinogen and platelets rapidly saturate the exposed subendothelium of a freshly deendothelialized aorta in vivo. As thrombin generated within the site of injury is largely responsible for fibrin(ogen) deposition, we questioned whether various anticoagulant treatments would inhibit uptake of both fibrinogen and platelets in vivo. Rabbits were anticoagulated by pretreatment with either Warfarin, Ancrod, or recombinant hirudin. Each anesthetized, anticoagulated (or saline-injected control) rabbit was injected IV with rabbit 51 Cr-platelets and 125 I-fibrinogen before a balloon-catheter deendothelializing (or sham) injury of the thoracic aorta. At 10 minutes after injury, the rabbit was exsanguinated and the aorta excised. Platelet adsorption by the deendothelialized aorta surface was substantially reduced in anticoagulated rabbits (controls, 2.2ϫ10 5 /mm 2 ; Warfarin-treated, 1.2ϫ10 5 /mm 2 ; Ancrod-treated, 5.3ϫ10 4 /mm 2 ; r-hirudin-treated [5 mg/kg], 5.3ϫ10 4 /mm 2 ), and a significant reduction of fibrinogen associated with the platelet 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 the r-hirudin-and Warfarin-treated rabbits. The pattern of aorta-deposited 51 Cr-platelets and 125 I-fibrin in the anticoagulated rabbits corresponded well with an assessment by transmission electron microscopy of aortic tissue samples. We conclude that Ϸ70% of fibrinogen uptake is thrombin dependent and that Ϸ80% of platelet adsorption depends on codeposited fibrin(ogen) during the 10-minute interval after balloon injury. Pretreatment with an agent that interferes with either thrombin or fibrin production will inhibit the immediate interaction of fibrinogen and platelets with the freshly exposed subendothelium. (Arterioscler Thromb Vasc Biol. 1998;18:816-824.)

No abstract