Sat, 05 Jul 2008 22:48:59 BST CiteULike: matthewhflamm's shear_flow http://www.citeulike.org/user/matthewhflamm/tag/shear_flow CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/matthewhflamm/article/2683123 <i>Biophys. J., Vol. 56, No. 6. (1 December 1989), pp. 1121-1141.</i><br /><br />The concentration profiles of adenosine diphosphate (ADP), thromboxane A2 (TxA2), thrombin, and von Willebrand factor (vWF) released extracellularly from the platelet granules or produced metabolically on the platelet membrane during thrombus growth, were estimated using finite element simulation of blood flow over model thrombi of various shapes and dimensions. The wall fluxes of these platelet-activating agents were estimated for each model thrombus at three different wall shear rates (100 s-1, 800 s-1, and 1,500 s-1), employing experimental data on thrombus growth rates and sizes. For that purpose, whole human blood was perfused in a parallel-plate flow chamber coated with type l fibrillar human collagen, and the kinetic data collected and analyzed by an EPl-fluorescence video microscopy system and a digital image processor. It was found that thrombin concentrations were large enough to cause irreversible platelet aggregation. Although heparin significantly accelerated thrombin inhibition by antithrombin lll, the remaining thrombin levels were still significantly above the minimum threshold required for irreversible platelet aggregation. While ADP concentrations were large enough to cause irreversible platelet aggregation at low shear rates and for small aggregate sizes, TxA2 concentrations were only sufficient to induce platelet shape change over the entire range of wall shear rates and thrombi dimensions studied. Our results also indicated that the local concentration of vWF multimers released from the platelet alpha-granules could be sufficient to modulate platelet aggregation at low and intermediate wall shear rates (less than 1,000 s-1). The sizes of standing vortices formed adjacent to a growing aggregate and the embolizing stresses and the torque, acting at the aggregate surface, were also estimated in this simulation. It was found that standing vortices developed on both sides of the thrombus even at low wall shear rates. Their sizes increased with thrombus size and wall shear rate, and were largely dependent upon thrombus geometry. The experimental observation that platelet aggregation occurred predominantly in the spaces between adjacent thrombi, confirmed the numerical prediction that those standing vortices are regions of reduced fluid velocities and high concentrations of platelet-activating substances, capable of trapping and stimulating platelets for aggregation. The average shear stress and normal stress, as well as the torque, acting to detach the thrombus, increased with increasing wall shear rate. Both stresses were found to be nearly independent of thrombus size and only weekly dependent upon thrombus geometry. Although both stresses had similar values at low wall shear rates, the average shear stress became the predominant embolizing stress at high wall shear rates. Mathematical analysis of mural thrombogenesis. Concentration profiles of platelet-activating agents and effects of viscous shear flow. BJ Folie LV Mcintire Biophys. J., Vol. 56, No. 6. (1 December 1989), pp. 1121-1141. 2008-04-17T18:24:40-00:00 1989 Biophys. J. 56 6 1121 1141 concentration_profile platelet shear_flow http://www.citeulike.org/user/matthewhflamm/article/2683050 <i>Thrombosis and Haemostasis, Vol. 99, No. 1. (January 2008), pp. 108-115.</i><br /><br />We propose a method to analyze platelet adhesion and aggregation computationally, taking into account the distinct properties of two plasma proteins, vonWillebrand factor (vWF) and fibrinogen (Fbg). In this method, the hydrodynamic interactions between platelet particles under simple shear flow were simulated using Stokesian dynamics based on the additivity of velocities. The binding force between particles mediated by vWF and Fbg was modeled using the Voigt model.Two Voigt models with different properties were introduced to consider the distinct behaviors of vWF and Fbg. Our results qualitatively agreed with the general observation of a previous in-vitro experiment, thus demonstrating that the significant development of thrombus formation in height requires not only vWF, but also Fbg. This agreement of simulation and experimental results qualitatively validates our model and suggests that consideration of the distinct roles of vWF and Fbg is essential to investigate the physiological and pathophysiological mechanisms of thrombus formation using a computational approach. Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor Daisuke Mori Koichiro Yano Ken-Ichi Tsubota Takuji Ishikawa Shigeo Wada Takami Yamaguchi Thrombosis and Haemostasis, Vol. 99, No. 1. (January 2008), pp. 108-115. 2008-04-17T17:43:29-00:00 2008 Thrombosis and Haemostasis 99 1 108 115 computational_simulation glycoprotein_receptors shear_flow thrombus