A COMPUTATIONAL ANALYSIS OF FXA GENERATION BY TF-FVIIA ON THE SURFACEOF RAT VASCULAR SMOOTH-MUSCLE CELLS

A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activat ion by the tissue factor-factor Wa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared t o previously obtained experimental data for the generation of factor X a (FXa) by TF:VIIa on the surface of cultured rat vascular smooth musc le cells. In this study, the complete steady-state convection-diffusio n equation was solved using the commercial software package, FLUENT (F luent Inc., Lebanon, New Hampshire). A user-defined subroutine interfa ced with FLUENT implemented the surface reaction which was modeled usi ng classical Michaelis-Menten reaction kinetics. The numerical solutio ns were obtained for 12 cases which used combinations of three wall sh ear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ra nged from classical kinetic reaction control (no dependence) to pure d iffusional control (maximum dependence). The experimental data, howeve r, were not represented by numerical data generated using a single rea ction rate. The three numerically obtained fluxes which corresponded m ost closely to the experimental fluxes were determined using three dif ferent V-max values. This finding supports the hypothesis that there m ay be a direct effect of how on the TF:VIIa complex or the cell membra ne. (C) 1998 Biomedical Engineering Society. [S0090-6964(98)00702-4].