Browsing by Subject "shear rate"
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Item Open Access Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa(2010) Shibeko, Alexey M; Lobanova, Ekaterina S; Panteleev, Mikhail A; Ataullakhanov, Fazoil IBackground: Blood coagulation is a complex network of biochemical reactions, which is peculiar in that it is time- and space-dependent, and has to function in the presence of rapid flow. Recent experimental reports suggest that flow plays a significant role in its regulation. The objective of this study was to use systems biology techniques to investigate this regulation and to identify mechanisms creating a flow-dependent switch in the coagulation onset. Results: Using a detailed mechanism-driven model of tissue factor (TF)-initiated thrombus formation in a two-dimensional channel we demonstrate that blood flow can regulate clotting onset in the model in a threshold-like manner, in agreement with existing experimental evidence. Sensitivity analysis reveals that this is achieved due to a combination of the positive feedback of TF-bound factor VII activation by activated factor X (Xa) and effective removal of factor Xa by flow from the activating patch depriving the feedback of "ignition". The level of this trigger (i.e. coagulation sensitivity to flow) is controlled by the activity of tissue factor pathway inhibitor. Conclusions: This mechanism explains the difference between red and white thrombi observed in vivo at different shear rates. It can be speculated that this is a special switch protecting vascular system from uncontrolled formation and spreading of active coagulation factors in vessels with rapidly flowing blood.Item Open Access Fluid Dynamics of a Centrifugal Left Ventricular Assist Device(2010) Selgrade, Brian PaulHigh shear stresses and shear rates in left ventricular assist devices (LVADs) make endothelialization of the LVAD difficult and likely contribute to cleavage of large von Willebrand factor multimers and resulting bleeding problems in patients. To better understand shear in a centrifugal LVAD, flow was simulated using finite volume and computational fluid dynamics (CFD) analysis. The k-ω model simulated turbulence and sliding meshes were used to model the movement of the impeller. CFD results showed high-shear backflows in the radial gap between the impeller and the volute wall, but residence times in this region were under 5ms. It is unclear if this is sufficient to cleave VWF, and more study is necessary to determine if other areas in the LVAD have potential for VWF cleavage. Although the walls near the outlet experience low shear stress and may be good candidates for endothelialization, shear stresses above 20-30Pa on all other walls of the pump make the possibility of endothelial cell growth elsewhere in the LVAD unlikely. An LVAD designed specifically to have low shear may be a better candidate for endothelialization.