Effect of red blood cells on shear-induced platelet activation: a micro-scale computational...
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$296 Journal of Biomechanics 2006, Vol. 39 (Suppl 1) Oral Presentations in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a plasma loss of 280m1. Additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. These results suggest that capillary filtration may play a key role in producing POI and that development of countermeasures may need to focus on reducing postflight capillary permeability or on stimulating volume-compensating mechanisms. 4636 We, 14:00-14:30 (P34) Computational modeling of arterial platelet thrombosis in stenotic vessels A. Fogelson 1,2, R.D. Guy 1. 1Department of Mathematics and 2Department of Bioengineering, University of Utah, Salt Lake City, UT, USA Intravascular hemostasis and thrombosis occur under flow and this can pro- foundly influence the progress of clot formation. This talk will focus on one of our efforts to model and probe the interactions of flow and thrombosis. It involves a continuum model that describes platelet thrombosis initiated by a ruptured atherosclerotic plaque in a coronary-artery-sized vessel. This model includes full treatment of the fluid dynamics, the development of platelet thrombi in response to the plaque rupture and further chemical signals, and the feedback of the growing thrombi on the fluid motion. The full model treats events on two spatial scales, the millimeter scale of the vessel and the micron scale of the platelets. An approximate closure version of the model allows elimination of the smaller scale while retaining important features, such as strain-dependent embolization, of the full model. Among the behaviors seen with this model are the growth of wall-adherent platelet thrombi to occlude the vessel and stop the flow, and the transient growth and subsequent embolization of thrombi leaving behind a passivated injured surface. 4835 We, 14:30-14:45 (P34) Multiscale modeling of blood flow: coupling of dissipative particle method and finite element method M. Kojic 1,2, N. Filipovic 1,2, A. Tsuda 1. 1Harvard School of Public Health, Boston MA, USA, 2 University of Kragujevac, Serbia To investigate the interplay between macroscale hemodynamic and microscale molecular/cellular processes, it is often necessary to consider phenomena si- multaneously occurring in multiple distinctly different scales. We have extended the bridging scale method proposed by Liu and coworkers (Wagner and Liu, Comp. Meth. Appl. Mech. Eng. 190: 249-274, 2003) to couple the meso-scale dissipative particle (DPD) method and Navier-Stockes equations discretized by the finite element (FE) method. We call this method the mesoscopic bridging scale method (MBSM). The basis of this method lies in the idea that fluid velocities can be decomposed into fine and coarse scales. It can be shown that by using the appropriate projection operator, the kinetic energy of these two scales can be expressed uncoupled. On the other hand, the internal forces in the two scales are mutually dependent. Therefore, the differential equations of motion of these two scales are coupled through internal forces (stresses). We have used this newly developed MBSM to model a large arterial bifurcation flow in which a pronounced local flow disturbance with large shear stress gradient near the wall often triggers plaque development. We have compared our multiscale MBSM solutions with the continuum-based FE solutions and demonstrated the advantages offered by the multiscale approach over the traditional FE approach. Supported by NIH HL054885, and HL070542. 4346 We, 14:45-15:00 (P34) Effect of red blood cells on shear-induced platelet activation: a micro-scale computational simulation T. Almomani 1, J.S. Marshall 2, K.B. Chandran 1. 1Department of Biomedical Engineering 2 and Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA, USA High hemodynamic shear stress in flow through mechanical heart valves and in other vascular implants is correlated with high incidence of thrombus forma- tion [1]. The current study examines shear stresses and activation potential of platelets passing through constricted flow regions typical of mechanical valves. The research focuses on the effect of the surrounding RBCs on modulat- ing shear-induced platelet activation. A computational fluid dynamics (CFD) model has been developed to perform microscale numerical experiments on RBC/platelet interaction. The CFD model employs a level-set based sharp- interface immersed-boundary method in which RBC and platelet boundaries are advected on Cartesian grid system [2]. RBCs are assumed to have an elliptical shape which deforms homogenously under fluid forces. Forces and torques between colliding blood cells are modeled using an extension of the soft-sphere model for elliptical particles. RBCs and platelets are transported under the forces and torques induced by the fluid flow and cell collisions based on solving a momentum equation for each blood cell. The current computations are simplified by restriction to two-dimensional, incompressible flow. The computations are used to determine the time shear history on platelets as they pass through high-constriction flow regions under different hematocrit levels, which are used to evaluate the influence of RBCs on different measures of shear-induced platelet activation. The computational results are also used to compare the average streamwise drag and lateral dispersion of platelets when immersed in blood at different hematocrit levels with that observed for platelets in plasma alone. References [1] A.P. Yoganathan, K.B. Chandran, E Sotiropoulos. Flow in prosthetic heart valves: state-of-the-art and future directions. Ann. Biomed. Eng. 2005; 33(12): 1689-1694. [2] S. Marella, S. Krishnan, H. Liu, H.S. Udaykumar. Sharp interface Cartesian grid method I: An easily implemented technique for 3D moving boundary computations. J. Comput. Phys. 2005; 210(1): 1-31. 5267 We, 15:00-15:15 (P34) A time-dependent model for shear stress induced ATP release from vascular endothelial cells K.-R. Qin 1, Z. Xu 3, H. Zhang 3, C. Xiang 2, S.S. Ge 2, Z.-L. Jiang 1. 1Institute of Mechanobiology & Medical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 2Department of Electrical and Computer Engineering, National University of Singapore, 3Institute of Biomechanics, Fudan University, Shanghai, China In consideration of time dependency of shear stress induced ATP release from vascular endothelial cells (ECs), a novel time-dependent mathematical model for shear stress induced ATP release from ECs was first proposed. Solving its verse problem based on experimental data for shear stress induced ATP release from human pulmonary artery endothelial cells by Yamamoto et al, we obtained all the constants in the model. The synergistic effects of shear stress modulation, convection-diffusion, and ATP hydrolysis on the ATP concentration at surface of cultured ECs at the bottom of parallel-plate flow chamber were studied based on the ATP release model. The results demonstrate that the predicted apparent ATP release rate against time shows good agreement with experimental data when the initial ATP concentration in the perfusate is zero; shear stress obviously mediates the ATP concentration at endothelial surface; the ATP concentration at endothelial surface is dependent on shear stress rather than shear rate in the initial stage of shear stress acting on ECs while the ATP concentration at endothelial surface is dependent on shear stress and shear rate in the later stage of shear stress acting on ECs. It is concluded that the time-dependent model is reasonable on the one hand, the shear stress modulation, convention-diffusion of ATP and ATP hydrolysis synergistically determine the ATP concentration at endothelial surface against time on the other hand. This research was supported by grants from National Natural Science Foun- dation of China, No. 10472027, No. 10132020. 4730 We, 15:15-15:30 (P34) Effect of pressure on arterial vasomotion M. Koenigsberger 1, R. Sauser 1, J.L. B6ny 2, J.J. Meister 1. 1Laboratory of Cell Biophysics, Ecole Polytechnique F~d~rale de Lausanne, Switzerland, 2Department of Zoology and Animal Biology, University of Geneva, Switzerland Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress like intraluminal pressure variations. An increase in pressure is able to induce a vessel contraction, a phenomenon called the myogenic response. Pressure changes have been observed to modulate the rhythmic diameter oscillations of the vessel (vasomotion). Vasomotion is caused by synchronous calcium oscillations of the smooth muscle cells. To get a better un- derstanding of the effect of stress and in particular pressure on vasomotion, we propose a model describing the calcium dynamics in a population of coupled smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that an increase in pressure induces an increase in the calcium concentration and may move the smooth muscle cells from a steady state domain to an oscillatory domain, and vice versa. In the oscillatory domain, a population of coupled smooth muscle cells exhibits synchronous calcium oscillations. Outside the oscillatory domain, the coupled smooth muscle cells present only irregular calcium flashings arising from stochastic opening of channels. Within the oscillatory domain, an increase in pressure increases the frequency of vasomotion. In our model a higher vasoconstrictor concentration may be needed to induce vasomotion in large arteries, and large arteries may oscillate at a lower frequency than smaller arteries when stimulated with the same vasoconstrictor concentration. Moreover our results show that the myogenic response is less pronounced for large arteries than for small arteries
Transcript of Effect of red blood cells on shear-induced platelet activation: a micro-scale computational...
$296 Journal o f Biomechanics 2006, Vol. 39 (Suppl 1) Oral Presentat ions
in arterial pressure sufficient to compromise cerebral perfusion and, therefore, cause syncope was reached in about 7 min with a plasma loss of 280m1. Additional simulations showed that a 75% increase in peripheral resistance, similar to finishers of stand tests, was insufficient to overcome the loss of circulating fluid associated with capillary filtration, and extended the time that the modeled astronaut could stand by only about 1 min. These results suggest that capillary filtration may play a key role in producing POI and that development of countermeasures may need to focus on reducing postflight capillary permeability or on stimulating volume-compensating mechanisms.
4636 We, 14:00-14:30 (P34) Computat ional model ing of arterial platelet th rombosis in stenot ic vessels A. Fogelson 1,2, R.D. Guy 1 . 1Department of Mathematics and 2Department of Bioengineering, University of Utah, Salt Lake City, UT, USA
Intravascular hemostasis and thrombosis occur under flow and this can pro- foundly influence the progress of clot formation. This talk will focus on one of our efforts to model and probe the interactions of flow and thrombosis. It involves a continuum model that describes platelet thrombosis initiated by a ruptured atherosclerotic plaque in a coronary-artery-sized vessel. This model includes full treatment of the fluid dynamics, the development of platelet thrombi in response to the plaque rupture and further chemical signals, and the feedback of the growing thrombi on the fluid motion. The full model treats events on two spatial scales, the millimeter scale of the vessel and the micron scale of the platelets. An approximate closure version of the model allows elimination of the smaller scale while retaining important features, such as strain-dependent embolization, of the full model. Among the behaviors seen with this model are the growth of wall-adherent platelet thrombi to occlude the vessel and stop the flow, and the transient growth and subsequent embolization of thrombi leaving behind a passivated injured surface.
4835 We, 14:30-14:45 (P34) Mult iscale model ing o f b lood f low: coupl ing o f d iss ipat ive part icle method and f inite e lement method M. Kojic 1,2, N. Filipovic 1,2, A. Tsuda 1 . 1Harvard School of Public Health, Boston MA, USA, 2 University of Kragujevac, Serbia
To investigate the interplay between macroscale hemodynamic and microscale molecular/cellular processes, it is often necessary to consider phenomena si- multaneously occurring in multiple distinctly different scales. We have extended the bridging scale method proposed by Liu and coworkers (Wagner and Liu, Comp. Meth. Appl. Mech. Eng. 190: 249-274, 2003) to couple the meso-scale dissipative particle (DPD) method and Navier-Stockes equations discretized by the finite element (FE) method. We call this method the mesoscopic bridging scale method (MBSM). The basis of this method lies in the idea that fluid velocities can be decomposed into fine and coarse scales. It can be shown that by using the appropriate projection operator, the kinetic energy of these two scales can be expressed uncoupled. On the other hand, the internal forces in the two scales are mutually dependent. Therefore, the differential equations of motion of these two scales are coupled through internal forces (stresses). We have used this newly developed MBSM to model a large arterial bifurcation flow in which a pronounced local flow disturbance with large shear stress gradient near the wall often triggers plaque development. We have compared our multiscale MBSM solutions with the continuum-based FE solutions and demonstrated the advantages offered by the multiscale approach over the traditional FE approach. Supported by NIH HL054885, and HL070542.
4346 We, 14:45-15:00 (P34) Effect o f red b lood cells on shear- induced platelet act ivat ion: a micro-scale computat ional s imulat ion
T. Almomani 1 , J.S. Marshall 2, K.B. Chandran 1 . 1Department of Biomedical Engineering 2 and Department of Mechanical and Industrial Engineering, The University of Iowa, Iowa City, IA, USA
High hemodynamic shear stress in flow through mechanical heart valves and in other vascular implants is correlated with high incidence of thrombus forma- tion [1]. The current study examines shear stresses and activation potential of platelets passing through constricted flow regions typical of mechanical valves. The research focuses on the effect of the surrounding RBCs on modulat- ing shear-induced platelet activation. A computational fluid dynamics (CFD) model has been developed to perform microscale numerical experiments on RBC/platelet interaction. The CFD model employs a level-set based sharp- interface immersed-boundary method in which RBC and platelet boundaries are advected on Cartesian grid system [2]. RBCs are assumed to have an elliptical shape which deforms homogenously under fluid forces. Forces and torques between colliding blood cells are modeled using an extension of the soft-sphere model for elliptical particles. RBCs and platelets are transported
under the forces and torques induced by the fluid flow and cell collisions based on solving a momentum equation for each blood cell. The current computations are simplified by restriction to two-dimensional, incompressible flow. The computations are used to determine the time shear history on platelets as they pass through high-constriction flow regions under different hematocrit levels, which are used to evaluate the influence of RBCs on different measures of shear-induced platelet activation. The computational results are also used to compare the average streamwise drag and lateral dispersion of platelets when immersed in blood at different hematocrit levels with that observed for platelets in plasma alone.
References [1] A.P. Yoganathan, K.B. Chandran, E Sotiropoulos. Flow in prosthetic heart
valves: state-of-the-art and future directions. Ann. Biomed. Eng. 2005; 33(12): 1689-1694.
[2] S. Marella, S. Krishnan, H. Liu, H.S. Udaykumar. Sharp interface Cartesian grid method I: An easily implemented technique for 3D moving boundary computations. J. Comput. Phys. 2005; 210(1): 1-31.
5267 We, 15:00-15:15 (P34) A t ime-dependent model for shear stress induced ATP release from vascular endothel ia l cel ls K.-R. Qin 1 , Z. Xu 3, H. Zhang 3, C. Xiang 2, S.S. Ge 2, Z.-L. Jiang 1 . 1Institute of Mechanobiology & Medical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 2Department of Electrical and Computer Engineering, National University of Singapore, 3Institute of Biomechanics, Fudan University, Shanghai, China
In consideration of time dependency of shear stress induced ATP release from vascular endothelial cells (ECs), a novel time-dependent mathematical model for shear stress induced ATP release from ECs was first proposed. Solving its verse problem based on experimental data for shear stress induced ATP release from human pulmonary artery endothelial cells by Yamamoto et al, we obtained all the constants in the model. The synergistic effects of shear stress modulation, convection-diffusion, and ATP hydrolysis on the ATP concentration at surface of cultured ECs at the bottom of parallel-plate flow chamber were studied based on the ATP release model. The results demonstrate that the predicted apparent ATP release rate against time shows good agreement with experimental data when the initial ATP concentration in the perfusate is zero; shear stress obviously mediates the ATP concentration at endothelial surface; the ATP concentration at endothelial surface is dependent on shear stress rather than shear rate in the initial stage of shear stress acting on ECs while the ATP concentration at endothelial surface is dependent on shear stress and shear rate in the later stage of shear stress acting on ECs. It is concluded that the time-dependent model is reasonable on the one hand, the shear stress modulation, convention-diffusion of ATP and ATP hydrolysis synergistically determine the ATP concentration at endothelial surface against time on the other hand. This research was supported by grants from National Natural Science Foun- dation of China, No. 10472027, No. 10132020.
4730 We, 15:15-15:30 (P34) Effect of pressure on arterial vasomot ion
M. Koenigsberger 1 , R. Sauser 1 , J.L. B6ny 2, J.J. Meister 1. 1Laboratory of Cell Biophysics, Ecole Polytechnique F~d~rale de Lausanne, Switzerland, 2Department of Zoology and Animal Biology, University of Geneva, Switzerland
Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress like intraluminal pressure variations. An increase in pressure is able to induce a vessel contraction, a phenomenon called the myogenic response. Pressure changes have been observed to modulate the rhythmic diameter oscillations of the vessel (vasomotion). Vasomotion is caused by synchronous calcium oscillations of the smooth muscle cells. To get a better un- derstanding of the effect of stress and in particular pressure on vasomotion, we propose a model describing the calcium dynamics in a population of coupled smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that an increase in pressure induces an increase in the calcium concentration and may move the smooth muscle cells from a steady state domain to an oscillatory domain, and vice versa. In the oscillatory domain, a population of coupled smooth muscle cells exhibits synchronous calcium oscillations. Outside the oscillatory domain, the coupled smooth muscle cells present only irregular calcium flashings arising from stochastic opening of channels. Within the oscillatory domain, an increase in pressure increases the frequency of vasomotion. In our model a higher vasoconstrictor concentration may be needed to induce vasomotion in large arteries, and large arteries may oscillate at a lower frequency than smaller arteries when stimulated with the same vasoconstrictor concentration. Moreover our results show that the myogenic response is less pronounced for large arteries than for small arteries
