To elaborate the mathematic model of fibrin lysis by plasmin (Pm) discribing this process as dissolution of the clot from its surface we assumed that: 1) fibrin clot is uniform, semi-infinite cylinder separated from liquid phase by the flat boundary with an invariable area in time; 2) lysis of the fibrin layer by fibrin-specific Pm proceeds more rapidly than the enzyme diffusion into the clot; 3) rate of superficial fibrinolysis dépendes on concentration of Pm bound to fibrin; 4) correlation between concentrations of Pm bound per unit of fibrin fiber surface and free Pm is described by Langmuir equation. The offered model leads to the next equation of the change of coordinate X - the clot surface boundary with liquid phase: dX/dt = 1/ρFn × keffKaCPm/1+KaCPm, where Ka - adsorbtion constant; ρFn - fibrin fiber density; keff = kcat Θ0 - effective rate constant of fibrinolysis; Θ0 - potential concentration of Pm binding sites on fibrin surface. The model was used for the analysis of experimental data obtained by measuring the kinetics of fibrin clot boundary change during the lysis by Pm. It was found parameters of the model were found: Ka = 10 mkM-1 and keff = 0.95 mg/(cm2min). The model describes rather adequately the experimental kinetic curves of lysis at different fibrin densities and Pm concentrations (50 - 1000 nM). The model which was extended by introduction of the Pm inhibition with fibrin degradation products describes also unlinear kinetic curves of lysis observed at lower Pm consentrations (<50nM). The found inhibition constant Ki was 0.5 mkM.
|Original language||English (US)|
|Number of pages||1|
|Journal||Fibrinolysis and Proteolysis|
|Issue number||SUPPL. 1|
|State||Published - Dec 1 1998|
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