чyвcтвитeльнocть к cпeцифичecким ингибитopaм paннич и пoзднич cтaдии caмocбopки фибpинa

Fibrinogen and its degradation products - specific inhibitors of fibrin polymerization, were added to dissolved fibrin prior to or during polymerization. Inhibitor additions were timed so as to cover the whole period of polymerization up to the outset of clotting. The results clearly demonstrated that when the addition delay was gradually increased the inhibitory effect decreased much sharper than expected, i.e. the actual retardation of clotting proved less than the value calculated on the admission that all the polymerization stages were equally susceptible. (In the Table I figures represent seconds of clotting retardation; column 3 - found, column 4 - calculated). At the latest polymerization stages the inhibitory effect vanished altogether. Both of the manifestations of the inhibitory activity, prolonged clotting time and deminished gel turbidity, subsided in parallel as the moment of inhibitor introduction was moving towards the moment of clotting. FIG. 1 shows turbidity increase during the clotting of two fibrin monomer preparations one of which (A) had been preliminarily activated (14); the upper curve corresponds to the inhibitor-free controle, the lowest curve - to the sample containing the inhibitor from the very beginning of the polymerization, the intermediate curve - a sample to which the inhibitor was added with a delay equal to 50% of the controle clotting time. Fibrinogen labelled with fluoresceineisothiocyanate was found to be incorporated into fibrin clot more readily at early polymerization stages. Electron microscopic examination revealed striking structural defects in fibrin fibres whose formation was influenced by the inhibitor throughout the polymerization process. If added at later stages the inhibitor caused little or no structural damage (FIG. 2–5). Thus, the susceptibility to specific inhibitors disappeares to a great extent during the early polymerization stages. In contrast with the specific inhibitors other inhibitors, like urea or hexamethylene glycol, are fully effective even if applied just before clotting would began. This striking difference suggest that the early and late polymerization stages differ from each other in respect to molecular mechanisms involved.     

Знaчeниe AКTГ для пroцecca oбraзoвaния кomплeкcныч coeдинeний гeпarинa в кroви пrи иmmoбилизaциoннom cтrecceThe role of ACTH in the formation of heparin complexes in blood under immobilization stress conditions

Under stress condition due to 30 min immobilization the total non-enzymatic fibrinolytic activity in rats is increased 4-fold, its proportion in the overall fibrinolytic activity of blood plasma being increased 1,5-fold. After pretreatment with ACTH (5–15 units) the same stress leads to more significant increase of non-enzymatic fibrinolysis which is 2,5 times higher than that in the absence of ACTH. The activity of fibrinogenheparin, epinephrineheparin, plasminogenheparin and plasminheparin complexes is increased 1,5–2,5 fold. ACTH induced a more efficient formation of heparin complexes also in the absence of stress. Its action is revealed in the course of 24 hours. Under blocked ACTH secretion as a result of DOCA treatment immobilization stress does not followed by increase of complex formation. The effect of ACTH on the formation of heparin complexes is mediated by stimulation of the adrenal cortex and by an increase in the corticosteroid level in the organism. Evidence of this has been produced from experiments on rats using ACTH treatment at different intervals after adrenalectomy. During first 24 hours after adrenalectomy when the additional cortical tissue is yet not active the injection of ACTH does not intensify heparin complexes formation. In 96 hours after adrebalectomy additional cortical tissue already responds to ACTH and accordingly stress after pretreatment with ACTH results in a greater increase of non=enzymatic fibrinolytic activity than that without ACTH.