Effect of heparin on the vascular distribution of *I-antithrombin III isoforms in rabbits

Studies of radioiodinated antithrombin III kinetic behavior in vivo have shown that a pool of this protein partitions into a vascular compartment that could be the result of antithrombin III interaction with heparin-related glycosaminoglycans present on the vessel wall (J. Clin. Invest. 74, 191-191, 1984). As this partitioning was demonstrated by the rapid initial clearance of the labeled antithrombin III, new studies were performed to determine the effect on this clearance of large doses of intravenously administered heparin. In addition, as previous studies had shown unequal clearance rates for tracer-labeled antithrombin III isoforms differing in affinity for heparin, the effect of heparin treatment was assessed for each isoform. Comparison of data from heparin-treated and control animals demonstrated that heparin markedly decreased the clearance rates for each of the *I-labeled antithrombin III isoforms. Heparin also abolished the difference in *I-antithrombin III isoform plasma-clearance rates, and this effect rapidly disappeared after treatment was discontinued. Inhibition by heparin of the initial clearance of *I-labeled ATIII isoforms is the first direct evidence from in vivo studies for the notion that the pool of antithrombin III which is in rapid equilibrium with the plasma pool is, at least in part, the result of the interaction of antithrombin III with vessel wall heparin-related glycosaminoglycans.