Abstract. Rabbit antithrombin III (AT), purified by heparin-agarose, was labeled with iodine-131 by either the glucose oxidase-lactoperoxidase or iodine monochloride techniques. When intravenously injected, the disappearance of the '3'I-AT from plasma was characterized by rapid initial decreases, and three-exponential equations were required for best fit of the plasma disappearance curves. This rapid '3'I-AT removal was not caused by denaturation, as shown by comparison with results obtained when '3'I-AT was biologically screened (injected into a first rabbit, and then transferred 16 h later in whole plasma to a second for kinetic evaluation) before injection. Thus, the same rapid initial loss ofplasma '3'I-AT was observed with screened preparations, and the plasma fractional catabolic rates of 0.716±0.048 and 0.673±0.051 day-' for unscreened and screened '3'I-AT were not significantly different. These results support the hypothesis that a vascular-endothelial AT compartment is present in rabbit. The fractions of the total-body AT in the plasma, the vascular-endothelial and the extravascular compartments were 0.337±0.031, 0.178+0.056, and 0.485±0.069, respectively.Two three-compartment kinetic models are discussed. The first pictures AT as distributing independently between plasma and two other compartments, and the second sees AT as first passing to the vascular-endothelial compartment, and then directly into the extravascular

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The distribution and rates of catabolism were determined for rabbit antithrombin III (AT) isoforms differing in affinity for heparin-agarose. After isolation from rabbit plasma by heparin-affinity chromatography, the very-high-affinity form, ATvh, was labelled with 131I, and its high-affinity congener, ATh, with 125I. The two forms were separated from free iodine by heparin-affinity chromatography, and then injected simultaneously into young recipient rabbits. The disappearance-of-plasma-AT-radioactivity data were fitted to three exponential equations, and the resulting constants were used to calculate fractional catabolic rates and the various pool sizes for ATh and ATvh. The fractions of plasma ATh and ATvh catabolized daily (j3) were 0.763 +/- 0.023 and 1.88 +/- 0.057 day-1 respectively. Average values of jT, the daily fractional catabolic rates for the total-body ATh and ATvh, were 0.2633 +/- 0.0113 and 0.3832 +/- 0.0211 day-1. The ratios, ATh/ATvh, of the sizes of the plasma, non-circulating vascular-associated and extra-vascular compartments were 0.593, 0.990 and 1.30. By using a previous estimate of a 9:1 ATh/ATvh ratio in rabbit plasma and the calculated compartment sizes, the calculated relative ratio of ATh to ATvh was 5.4:1 in the non-circulating vascular-associated compartment. The data fit a model of antithrombin III distribution and catabolism in which a pool of endothelial-cell heparin-like receptors is seen to mediate the transfer of the inhibitor from plasma to interstitium with catabolism serving as an alternative to this transport.

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