COMPARATIVE METABOLISM AND DISTRIBUTION OF RABBIT HEPARIN-COFACTOR-IIAND RABBIT ANTITHROMBIN IN RABBITS

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 differentia lly radiolabeled (I-125, I-131) and injected intravenously; blood samp les were taken at prescribed intervals over 7 days. From the plasma cl earance curves of-protein-bound radioactivities, fractional catabolic rates and compartmental distributions were calculated using a three-co mpartment model. The whole body fractional catabolic rate for HCII (j( t), 0.43/day, equivalent to t(1/2) = 1.61 days) was significantly fast er than for AT (j(t), 0.37/day; t(1/2) = 1.89 days; P < 0.005). The fr actional distribution of HCII in the intravascular compartment (A(p), 0.20) and in the extravascular compartment (A(e), 0.63) differed signi ficantly from AT (A(p), 0.30; A(e), 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, equiv alent 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 similar to 1.4 at 2.5 h. This report increases our understanding of the in vivo dynamics of these two prote ins.