In vivo behavior of radioiodinated rabbit antithrombin III. Demonstration of a noncirculating vascular compartment.

Abstract

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

Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis.

“…There is no evidence of either genetic or phenotypic polymorphism of SAP.The behavior of the labeled isologous tracer used here can therefore be confidently taken to represent the behavior of autologous SAP in situ in the body. The fractional catabolic rate of SAP was -70% of the plasma pool per day, and it was therefore more rapidly catabolized in normal subjects than other plasma proteins studied hitherto (41)(42)(43)(44)(45)(46)(47). All the radioiodine-labeled breakdown products of the tracer were excreted in the urine and the injected dose was completely eliminated after -14 d. The estimated normal synthesis rate was -2 mg/h.…”

Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis

“…Large reductions of HS act might modestly perturb plasma AT levels, given that 10-20% of total body AT is sequestered by vascular endothelial HS act (38). Removal of this compartment could produce a slight elevation in plasma AT.…”

Effect of Heparin, Hirudin, and a Synthetic Thrombin Inhibitor on Antithrombin III in Thrombin-Induced Disseminated Intravascular Coagulation in Rats

“…The AT III may either be of the cir culating plasma pool or of the noncirculating vascular-associated compartment recently demonstrated by kinetic analyses in several species [10,11]. In rabbits, this compart ment amounts to nearly 20% of the total body AT III and shows a higher turnover then the latter [10]. It may be hypothesized that this 'active' AT III is complexed with thrombin first; the complex will then be re leased from the endothelial sites and elimi nated via the liver [7,35].…”

“…Reaction of thrombin with AT III may be catalyzed by vascular surfaceassociated heparin-like molecules [8,12,13,[32][33][34]. The AT III may either be of the cir culating plasma pool or of the noncirculating vascular-associated compartment recently demonstrated by kinetic analyses in several species [10,11]. In rabbits, this compart ment amounts to nearly 20% of the total body AT III and shows a higher turnover then the latter [10].…”