Track 19. B io t ranspor t

4445 Tu, 14:30-14:45 (P23) Effects o f shear-dependent t ranspor t propert ies on mass transfer in stenosed arteries N. Sun 1 , N.B. Wood 1 , A.D. Hughes 2, S.A. Thom 2, X.'~ Xu 1 . 1Department of Chemical Engineering, 2 NHLI, International Centre for Circulatory Health, St Mary's Hospital, Imperial College London, UK

Low wall shear stress (WSS), accumulation of low density lipoprotein (LDL) and hypoxia are considered as main contributing factors in atherogenesis. The present study focused on examining the influences of WSS on arterial mass transport by modelling the blood flow and solute transport in models of arterial stenosis. The effects of WSS on mass transfer have previously been investigated using a wall-free model [1], but coupled fluid-wall models incorporating shear-dependent transport properties have not been reported in the literature. We developed a fluid-wall model by including fluid dynamics of blood flow in the lumen and transmural flow in the wall, solute dynamics models for mass transport, and Kedem-Katchalsky equations for coupling at the endothelium. The arterial wall was treated as a single-layer of porous medium. Shear-dependent hydraulic conductivity for LDL transport [2] and permeability for oxygen transport [3] were based on experimental data. Both LDL accumulation and hypoxia in the arterial wall were found to co-localise with low WSS. It is shown that WSS affects LDL accumulation by a convective clearance mechanism in the wall [4], while oxygen transport is affected by WSS through shear-dependent diffusion at the endothelium, supporting the hypothesis that low WSS predicates atherogenesis.

References [1] Rappitsch G, Perktold K. Int. J. Numer. Methods Fluids 1997; 25: 847. [2] Sill HW, et al. Am. J. Physiol. Heart Circ. Physiol. 1995; 268: 535. [3] Liu CY, et al. In: Oxygen Transport to Tissue XV. 1992; New York: Plenum. [4] Tarbell JM, Annu. Rev. Biomed. Eng. 2003; 5: 79.

4799 Tu, 14:45-15:00 (P23) Invest igat ion o f pulsat i le mass t ranspor t in the downst ream graf t /ar tery junct ion o f per ipheral bypass grafts P.D. Devereux, T.P. O'Brien, M.T. Walsh, T.M. McGIoughlin. Centre for Applied Biomedical Engineering Research, Department of Mechanical and Aeronautical Engineering and The Materials and Surface Science Institute, University of Limerick, Limerick, Ireland

The development of intimal hyperplasia (IH) at the downstream junction of peripheral bypass grafts has been identified as one of the major contributors to the failure of this surgical intervention [1]. Previous studies into its initiation and progression have focused primarily on the non-physiological wall shear stress profiles at the bed of the junction and the compliance mismatch created by suturing a non-compliant graft to the host artery resulting in elevated wall stresses [2]. The objective of the current study is to progress from these theories of wall shear stress and altered wall mechanics. To this end, a computational investigation into the mass transport disturbances in the downstream junction was completed in an attempt to correlate locations of modified mass transport to regions of preferential IH development. The current computational study incorporated 3-dimensional representations of three idealised graft/artery junctions; the standard end-to-side, the Miller cuff and the Taylor patch [3], and one realistic model developed from MRI [4]. A pul- satile velocity boundary condition was prescribed at the inlet of all models [3]. The species of interest in the current study was platelet-derived growth factor (PDGF), a growth factor that has been implicated in IH development [2]. The transport of PDGF was modelled by solving the three-dimensional convection- diffusion equation. It was evident from the results of this study that the beds of all four geometries are subjected to a time-averaged increase in the transport of PDGR The bed is a primary location for IH development and it may be that an increase in the levels of PDGF at this location may contribute to IH initiation and progression.

References [1] Keynton R.S., et al. Journal of Biomechanical Engineering 2001; 123: 464-473. [2] Stewart S.F.C., Lyman D.J. Annals of Biomedical Engineering 2004; 32: 991-

1006. [3] O'Brien T. et al. Annals of Biomedical Engineering 2005; 33: 309-321. [4] http://www.ae.ic.ac.uk/staff/sherwin/Smiths/Case15/index.html.

4542 Tu, 15:00-15:15 (P23) eNOS and Ca 2* product ion in arterial geometries: An integrated f luid mechanics/cell model A. Comerford, M. Plank, T. David. Centre for Bioengineering, University of Canterbury, Christchurch, NZ

Arterial bifurcations and bends are regions of the human vasculature known to be prone to the formation of atherosclerosis; hence understanding how flow and blood borne agonists affect endothelial cellular responses, provide information about potential locations of Atherogenesis. In particular a reduction

19.3. Transport across Blood Vessel Walls II $375

in endothelial nitric oxide synthase (eNOS) signalling, which is responsible for the production of nitric oxide (NO), leads to reduced bioavailability of NO, which has been associated with endothelial dysfunction and subsequent complications [1]. The arterial geometries investigated were a 3D bend and bifurcations of varying angle (e=37.5 °, 75 °, 135°), this provides a detailed understanding about the effects geometry has on the transport of biochemical stimuli (ATP in the present study). The transport equations were solved using FLUENT CFD software, for Reynolds numbers of 200 and 500. The underlying cellular dynamics were incorporated utilising a set of ordinary differential equations developed by Plank et al [2]. The code for cellular response was linked to the CFD solver, taking wall shear stress (WSS) and ATP concentration as inputs and predicting the concentration of inositol trisphosphate, cytosolic calcium, stored calcium and eNOS. The results show, regions of low WSS and ATP Iocalised predominantly on the bifurcations outer wall, impaired calcium and eNOS signalling also occur in these locations; this observation is true irrespective of the bifurcation angle and Reynolds number. Smaller angle bifurcations lead to larger regions of reduced activity. Similarly, for the arterial bend reduced signalling occurs at the inner and outer wall; again these regions are subjected to low WSS and ATP concentration. The results have provided a spatial relationship between regions of low WSS, biochemical stimuli and reduced calcium/eNOS activity. These locations agree well with in vitro studies that demonstrate atherosclerosis is localized to these regions in the human vasculature.

References [1] Davignon and Ganz. Role of endothelial dysfunction in therosclerosis. Circula-

tion 2004; 109. [2] Plank et al. Atherosclerosis and calcium signalling in endothelial cells. Prog.

Biophys. Mol. Biol. 2005; doi:10.1016/j.pbiomolbio.2005.07.005.

7445 Tu, 15:15-15:30 (P23) Numerical model l ing o f macromolecular t ranspor t in a real ist ic moving model o f the r ight coronary ar tery

M.K. Kolandavel 1 , E.-T. Fruend 2, S. Ringgaard 2, EG. Walker 1 . 1School of Mechanical Engineering, University of Leeds, Leeds, UK, 2Institute of Clinical Medicine and MR Research Centre, Skejby Hospital, Aarhus, Denmark

The transport of macromolecular low density lipoprotein (LDL) from the blood to the arterial wall constitutes a major step in the formation of atherosclerosis. Since coronary arteries are most susceptible to atherosclerosis, we hypoth- esised that their unique cardiac-induced physiological motion may contribute to the disease and for the first time conducted a study to investigate its role on LDL transport. A realistic computational model of the right coronary artery (RCA) with a diameter of 3.9 mm was constructed from magnetic resonance images (MRI) of a healthy volunteer. A 1.5T Philips Intera (Philips Medical Systems, Best, The Netherlands) MRI scanner was used to acquire RCA geometry by applying a steady state free precession sequence (TR = 4.9 ms, TE=2.5ms, flip angle=60°). Based on the MRI measured RCA inlet flow and wall motion, numerical simulations of LDL transport with a concentration polarisation boundary condition were performed in the computational fluid dynamics software Fluent (v6.2.16, Fluent Inc., Lebanon, NH). To compare the effects of wall motion, a steady flow simulation (mean Re=64) in a static model of the RCA was also conducted. The dynamic model results predicted an elevation of up to 35% of inlet LDL concentration at the wall. The spatial distribution of LDL wall concentration varied considerably exhibiting local peaks in different regions of the model. Such regions were located on the inner side of local curvature where low wall shear stress (WSS) prevailed. Despite significant temporal changes in the WSS, LDL wall concentration varied moderately (<2%). However, where LDL concentration was as high as 20%, temporal variations in the order of 10-20% were noted. In the static model, LDL wall concentration continued to increase with distance from the inlet and its magnitude and spatial distribution were different to that in the dynamic model. These results suggest that the wall motion may play an important role in coronary arterial transport processes.

19.3. Transport across Blood Vessel Walls II

6794 Tu, 16:00-16:15 (P25) Effect o f f low d is turbance on ATP/ADP concentrat ion at the endothel ia l surface H.W. Choi, A.I. Barakat. Department of Mechanical and Aeronautical Engineering, University of California, Davis, USA

Knowledge of how fluid flow affects the concentration of the adenine nu- cleotides ATP and ADP at the vascular endothelial cell (EC) surface is impor- tant for understanding the regulation of intracellular calcium by flow. Previous mathematical models within parallel plate flow chambers had demonstrated that the combined nucleotide (ATP+ADP) concentration at the EC surface remains relatively constant over a wide range of wall shear stresses. Because