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  • Title: Catabolism of rabbit prothrombin in rabbits: uptake of prothrombin by the aorta wall before and after a de-endothelializing injury in vivo.
    Author: Hatton MW, Southward SM, Serebrin SD, Kulczycky M, Blajchman MA.
    Journal: J Lab Clin Med; 1995 Dec; 126(6):521-9. PubMed ID: 7490511.
    Abstract:
    After an injury to the vascular endothelium, certain blood proteins collect rapidly at the site of damage to prevent blood loss and maintain blood flow. The uptake of fibrinogen, plasminogen, and antithrombin--but not prothrombin--have been measured previously at the rabbit aorta wall after injury in vivo. This report describes the clearance of rabbit iodine 131-labeled prothrombin from the rabbit circulation to measure the distribution and fractional catabolic rate and compares the behavior of 131I-labeled prothrombin with either iodine 125-labeled fibrinogen or 125I-labeled antithrombin at the balloon catheter-injured aorta wall. When injected into young rabbits, 131I-labeled prothrombin was cleared from the intravascular space to yield a plasma curve that was best described by three exponentials. Fractional plasma and whole body catabolic rates were 2.0 day-1 and 0.41 day-1, respectively, equivalent to a catabolic half-life of 1.7 days. Fractional distribution of prothrombin amounted to 0.21, 0.24, and 0.55 within the intravascular, vascular endothelial, and extravascular compartments, respectively. Samples of 131I-labeled prothrombin and either 125I-labeled fibrinogen or 125I-labeled antithrombin were injected into anesthetized rabbits before balloon de-endothelialization of the thoracic aorta. The uptake of each radiolabeled protein by the aorta intima-media was measured at various times (5 to 60 minutes) after injury. Whereas uptake of plasma fibrinogen by the balloon-injured intima-media was maximal (20 pmol/cm2) in less than 5 minutes after injury, maximum uptake of prothrombin (5 to 6 pmol/cm2) took approximately 15 minutes. Uptake of prothrombin was initially faster than that of antithrombin, although approximately equimolar amounts of prothrombin and antithrombin were bound by the intimamedia by 60 minutes. The results are discussed in relation to thrombin production and the demand for antithrombin by the damaged aorta wall in vivo.
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