Comparative metabolism and distribution of rabbit heparin cofactor
-ii and rabbit antithrombin in rabbits.
Hatton, Mark W. C., Hugh Hoogendoorn, Suzanne M. R. Southward, Bonnie
Ross, and Morris A. Blajchman.
Department of Pathology, McMaster University Health Sciences
Centre, Hamilton ON L8N 3Z5, Canada, and Affinity Biologicals Inc.,
Hamilton ON L8V 1C3, Canada
APStracts 4:0017E, 1997.
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- 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 d-1, equivalent to T = 1.61 d) was
significantly faster than AT (jT, 0.37 d-1; T = 1.89 d;
p<0.005). The fractional distribution of HCII in the
intravascular compartment (Ap, 0.20) and in the extravascular
compartment (Ae, 0.63) differed significantly from AT (Ap, 0.30; Ae,
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 mg.d-1 and 19.9 mg.d-1 respectively, equivalent to a molar
ratio, AT/HCII, of 1.7. The catabolic molar ratio was compared to the
relative release rates of HCII and AT from perfused rabbit livers.
Both proteins were released from the liver, the molar ratio, AT/HCII,
in the perfusate rising to approximately 1.4 at 2.5h. This report
increases our understanding of the in vivo dynamics of these two
proteins.
Received 2 October 1996; accepted in final form 10 January 1997.
APS Manuscript Number E492-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997