Phasic flow patterns at a hemodialysis venous anastomosis

A phase-by-phase analysis of local flow patterns at the venous anastomosis of an arteriovenous hemodialysis angioaccess loop graft (AVLG) was made. The study was carried out in an elastic, transparent Silastic in vitro flow model, which duplicates the detail geometry of the AVLG obtained from an animal model (30+ kg dogs with 12 weeks bilateral femoral AVLG implantation). The flow model was installed in a mock pulsatile flow loop system designed to simulate physiological conditions. Flow visualization was made in laser-illuminated flow fields using a high-speed cine camera. Analysis of the high-speed cine indicates there is a distinct separation region downstream of the anastomotic toe in the median plane and a stagnation region that oscillates along the opposite wall. During inward motion of the vessel wall, accumulation of particles in the separation region and the nearby stagnation region is observed. A large swirl appears in the distal vein during end-systolic period. A double-helical flow pattern occurs further down in the distal vein. Retrograde flow in the distal vein occurs in an "oscillating" manner following each cardiac cycle.     

Flow profiles and wall shear stress distribution at a hemodialysis venous anastomosis: preliminary study

The phasic velocity field in the vicinity of the venous anastomosis in a hemodialysis angioaccess arteriovenous fistula loop graft (AVLG) is investigated employing a laser Doppler anemometer (LDA) system. Detailed LDA velocity profiles are obtained by sectional survey performed in a transparent, elastic flow model which was fabricated to represent the geometry of the AVLG system under physiological pressure and flow waveforms. The geometry of the flow model was based on a silicone rubber cast obtained from an experimental dog model. In the present study, detailed distribution of velocity profiles is obtained. The distribution of wall shear stress in the model is computed from the slope of the local velocity profiles near the wall. The relationship between the results obtained by flow visualization and the LDA measurement is discussed.     

The effect of angle and flow rate upon hemodynamics in distal vascular graft anastomoses: an in vitro model study.

A steady flow, in vitro model of distal arterial bypass graft junctions was used to examine the effects of junction angle and flow rate on the local velocity field. Three test sections were fabricated from Plexiglas tubing having anastomotic junction angles of either 30, 45, or 60 deg. Flow visualization revealed velocity profiles skewed toward the outer wall with a flow split around a clear stagnation point along the outer wall. Laser Doppler anemometry [LDA] measurements confirmed a distinct stagnation point at the outer wall and both reverse and forward shear were detected immediately upstream and downstream, respectively, of this site. Axial velocities and shear rates along the outer wall were higher than along the inner wall and occurred in the junction angle order: 45, 60, and 30 deg. This study clearly identified changes in wall shear which varied with the anastomotic angle and flow rate.     

Alteration of mean wall shear stress near an oscillating stagnation point.

The site opposite an end-to-side anastomosis, resulting from femoral bypass surgery, and the carotid sinus are two regions well known to be prone to fibrous intimal hyperplasia or atherogenesis, respectively. The blood flow at these two sites features a stagnation point, which oscillates in strength and position. Mathematical models are used to determine some of the features of such a flow; in particular, the mean wall shear stress is calculated. The positional oscillations cause a significant change in the distribution and magnitude of the mean wall shear stress from that of the well-studied case of a stagnation point that oscillates only in strength. It is therefore proposed that the recorded effect of time dependence in the flow upon atherogenesis could still be a result of the distribution of the mean and not the time-varying components of the wall shear stress.     

Characteristics of secondary flow in steady and pulsatile flows through a symmetrical bifurcation

Steady and pulsatile flow in a glass model simulating an arterial bifurcation was investigated by flow visualization techniques. Secondary flow generated at the bifurcation has a similar pattern to a vortex, called the horseshoe vortex, produced around a wall-based protuberance in a circular tube. The same flow disturbance was clearly observed during the decelerating phase of pulsatile flow. The vortex produces a stagnation point on the top and bottom wall just upstream from the bifurcation apex. When aluminium dust was suspended in the test fluid perfusing the blood vessel model, particles deposited over an area spreading from the stagnation point to the lateral corners of the bifurcation. Comparison between the present results and topographical patterns of atherosclerosis reported in the literature suggests that it is in such low shear regions that lipid deposition tends to occur most.     

Numerical analysis of hemodynamics in spastic middle cerebral arteries

Cerebral vasospasm (CVS) is the most common serious complication of subarachnoid hemorrhage. Among the many factors that are associated with the pathogenesis of CVS, hemodynamics plays an important role in the initiation and development of CVS. Numerical simulation was carried out to obtain the flow patterns and wall shear stress (WSS) distribution in spastic middle cerebral arteries. The blood was assumed to be incompressible, laminar, homogenous, Newtonian, and steady. Our simulations reveal that flow velocity and WSS level increase at the stenosis segment of the spastic vessels, but further downstream of stenosis, the WSS significantly decreases along the inner wall, and flow circulation and stagnation are observed. The hydrodynamic resistance increases with the increase of vessel spasm. Moreover, the change of flow field and hydrodynamic forces are not linearly proportional to the spasm level, and the rapid change of hemodynamic parameters is observed as the spasm is more than 50%. Accordingly, in the view of hemodynamic physiology, vessels with less than 30% stenosis are capable of self-restoration towards normal conditions. However, vessels with more than 50% stenosis may eventually lose their capacity to adapt to differing physiologic conditions due to the extreme non-physilogic hemodynamic environment, and the immediate expansion of the vessel lumen might be needed to minimize serious and non-reversible effects.     

Multiphysics simulation of blood flow and LDL transport in a porohyperelastic arterial wall model

Atherosclerosis localizes at a bend andor bifurcation of an artery, and low density lipoproteins (LDL) accumulate in the intima. Hemodynamic factors are known to affect this localization and LDL accumulation, but the details of the process remain unknown. It is thought that the LDL concentration will be affected by the filtration flow, and that the velocity of this flow will be affected by deformation of the arterial wall. Thus, a coupled model of a blood flow and a deformable arterial wall with filtration flow would be invaluable for simulation of the flow field and concentration field in sequence. However, this type of highly coupled interaction analysis has not yet been attempted. Therefore, we performed a coupled analysis of an artery with multiple bends in sequence. First, based on the theory of porous media, we modeled a deformable arterial wall using a porohyperelastic model (PHEM) that was able to express both the filtration flow and the viscoelastic behavior of the living tissue, and simulated a blood flow field in the arterial lumen, a filtration flow field and a displacement field in the arterial wall using a fluid-structure interaction (FSI) program code by the finite element method (FEM). Next, based on the obtained results, we further simulated LDL transport using a mass transfer analysis code by the FEM. We analyzed the PHEM in comparison with a rigid model. For the blood flow, stagnation was observed downward of the bends. The direction of the filtration flow was only from the lumen to the wall for the rigid model, while filtration flows from both the wall to the lumen and the lumen to the wall were observed for the PHEM. The LDL concentration was high at the lumenwall interface for both the PHEM and rigid model, and reached its maximum value at the stagnation area. For the PHEM, the maximum LDL concentration in the wall in the radial direction was observed at the position of 3% wall thickness from the lumenwall interface, while for the rigid model, it was observed just at the lumenwall interface. In addition, the peak LDL accumulation area of the PHEM moved about according to the pulsatile flow. These results demonstrate that the blood flow, arterial wall deformation, and filtration flow all affect the LDL concentration, and that LDL accumulation is due to stagnation and the presence of filtration flow. Thus, FSI analysis is indispensable.     

Computation in the rabbit aorta of a new metric – the transverse wall shear stress – to quantify the multidirectional character of disturbed blood flow

Spatial variation of the haemodynamic stresses acting on the arterial wall is commonly assumed to explain the focal development of atherosclerosis. Disturbed flow in particular is thought to play a key role. However, widely-used metrics developed to quantify its extent are unable to distinguish between uniaxial and multidirectional flows. We analysed pulsatile flow fields obtained in idealised and anatomically-realistic arterial geometries using computational fluid dynamics techniques, and in particular investigated the multidirectionality of the flow fields, capturing this aspect of near-wall blood flow with a new metric – the transverse wall shear stress (transWSS) – calculated as the time-average of wall shear stress components perpendicular to the mean flow direction. In the idealised branching geometry, multidirectional flow was observed downstream of the branch ostium, a region of flow stagnation, and to the sides of the ostium. The distribution of the transWSS was different from the pattern of traditional haemodynamic metrics and more dependent on the velocity waveform imposed at the branch outlet. In rabbit aortas, transWSS patterns were again different from patterns of traditional metrics. The near-branch pattern varied between intercostal ostia, as is the case for lesion distribution; for some branches there were striking resemblances to the age-dependent patterns of disease seen in rabbit and human aortas. The new metric may lead to improved understanding of atherogenesis.     

Model experiments on platelet adhesion in stagnation point flow

Experiments with glass models of arterial branchings and bends, perfused with bovine platelet rich plasma (PRP), revealed platelet deposition being strongly dependent on fluid dynamic factors. Predilection sites of platelet deposits are characterized by flow vectors directed against the wall, so-called stagnation point flow. Thus collision of suspended particles with the wall, an absolute prerequisite for adhesion of platelets to surfaces even as thrombogenic as glass, appears mediated by convective forces. The extent of platelet deposition is correlated to the magnitude of flow components normal to the surface as well as to the state of biological activation of the platelets. The latter could be effective by an increase in hydrodynamically effective volume, invariably associated with the platelet shape change reaction to biochemical stimulants like ADP. The effect of altered rheological properties of platelets upon their deposition and of mechanical properties of surfaces was examined in a stagnation point flow chamber. Roughnesses in the order of 5 microns, probably by creating local flow disturbances, significantly enhance platelet adhesion, as compared to a smooth surface of identical chemical composition.     

The influence of out-of-plane geometry on pulsatile flow within a distal end-to-side anastomosis

We present an experimental and computational investigation of time-varying flow in an idealized fully occluded 45 degrees distal end-to-side anastomosis. Two geometric configurations are assessed, one where the centerlines of host and bypass vessels lie within a plane, and one where the bypass vessel is deformed out of the plane of symmetry, respectively, termed planar and non-planar. Flow experiments were conducted by magnetic resonance imaging in rigid wall models and computations were performed using a high order spectral/hp algorithm. Results indicate a significant change in the spatial distribution of wall shear stress and a reduction of the time-averaged peak wall shear stress magnitude by 10% in the non-planar model as compared to the planar configuration. In the planar geometry the stagnation point follows a straight-line path along the host artery bed with a path length of 0.8 diameters. By contrast in the non-planar case the stagnation point oscillates about a center that is located off the symmetry plane intersection with the host artery bed wall, and follows a parabolic path with a 0.7 diameter longitudinal and 0.5 diameter transverse excursion. A definition of the oscillatory shear index (OSI) is introduced that varies between 0 and 0.5 and that accounts for a continuous range of wall shear stress vector angles. In both models, regions of elevated oscillatory shear were spatially associated with regions of separated or oscillating stagnation point flow. The mean oscillatory shear magnitude (considering sites where OSI>0.1) in the non-planar geometry was reduced by 22% as compared to the planar configuration. These changes in the dynamic behavior of the stagnation point and the oscillatory shear distribution introduced by out-of-plane graft curvature may influence the localization of vessel wall sites exposed to physiologically unfavorable flow conditions.     

Kinetics of specific and nonspecific adhesion of red blood cells on glass.

Fixed spherical human red blood cells suspended in 17% sucrose were allowed to adhere on either clean glass surfaces or glass surfaces preincubated with antibodies specific to a certain blood group antigen. The adhesion experiments were performed in an impinging jet apparatus, in which the cells are subjected to stagnation point flow. The objective of this study was to compare the efficiencies of nonspecific and specific (antigen-antibody mediated) adhesion of red blood cells on glass surfaces. The efficiency was defined as the ratio of the experimental adhesion rate to that calculated based on numerical solutions of the mass transfer equation, taking into account hydrodynamic interactions as well as colloidal forces. The efficiency for nonspecific adhesion was nearly unity at flow rates lower than 85 microliter/s (corresponding to a wall shear rate, Gw, of 30 s-1 at a radial distance of 110 microns from the stagnation point). The values of efficiency dropped at higher flow rates, due to an increase in the tangential force. The critical deposition concentration is found to occur at 120-150 mM NaCl, which is consistent with the theoretically predicted values. At low salt concentrations, the experimental values are higher than the theoretical ones. Similar discrepancies have been found in many colloidal systems. Introducing steric repulsion by adsorbing a layer of albumin molecules on the glass completely prevents nonspecific adhesion at flow rates below 60 microliter/s (Gw congruent to 15 s-1). The efficiency of specific adhesion depends both on the concentration of antibody molecules on the surface and the flow rate. Normal red cells adhere more readily through antigen-antibody bonds than fixed cells. Fixed spherical cells have a higher adhesion efficiency than fixed biconcave ones.     

A Microfluidic-based Hydrodynamic Trap for Single Particles

The ability to confine and manipulate single particles in free solution is a key enabling technology for fundamental and applied science. Methods for particle trapping based on optical, magnetic, electrokinetic, and acoustic techniques have led to major advancements in physics and biology ranging from the molecular to cellular level. In this article, we introduce a new microfluidic-based technique for particle trapping and manipulation based solely on hydrodynamic fluid flow. Using this method, we demonstrate trapping of micro- and nano-scale particles in aqueous solutions for long time scales. The hydrodynamic trap consists of an integrated microfluidic device with a cross-slot channel geometry where two opposing laminar streams converge, thereby generating a planar extensional flow with a fluid stagnation point (zero-velocity point). In this device, particles are confined at the trap center by active control of the flow field to maintain particle position at the fluid stagnation point. In this manner, particles are effectively trapped in free solution using a feedback control algorithm implemented with a custom-built LabVIEW code. The control algorithm consists of image acquisition for a particle in the microfluidic device, followed by particle tracking, determination of particle centroid position, and active adjustment of fluid flow by regulating the pressure applied to an on-chip pneumatic valve using a pressure regulator. In this way, the on-chip dynamic metering valve functions to regulate the relative flow rates in the outlet channels, thereby enabling fine-scale control of stagnation point position and particle trapping. The microfluidic-based hydrodynamic trap exhibits several advantages as a method for particle trapping. Hydrodynamic trapping is possible for any arbitrary particle without specific requirements on the physical or chemical properties of the trapped object. In addition, hydrodynamic trapping enables confinement of a "single" target object in concentrated or crowded particle suspensions, which is difficult using alternative force field-based trapping methods. The hydrodynamic trap is user-friendly, straightforward to implement and may be added to existing microfluidic devices to facilitate trapping and long-time analysis of particles. Overall, the hydrodynamic trap is a new platform for confinement, micromanipulation, and observation of particles without surface immobilization and eliminates the need for potentially perturbative optical, magnetic, and electric fields in the free-solution trapping of small particles.Download video file.^{(62M, mov)}     

Numerical 3D-simulation of pulsatile wall shear stress in an arterial T-bifurcation model

The structure of pulsatile blood flow and wall shear stress in a 90° T-bifurcation model is analysed numerically. The nonlinear Navier-Stokes equations for time-dependent incompressible Newtonian fluid flow are approximated using a newly developed pressure correction, finite element method. The wall shear stress is calculated from the finite element velocity field. The investigation shows viscous flow phenomena such as flow separation and stagnation and the distribution of high and low wall shear stress during the pulse cycle. Furthermore, the effect of a sharp corner the bifurcation edge on the wall shear stress is analysed. Detailed local flow investigation is required to examine fluid dynamic contribution to the development of arterial diseases such as atherosclerosis and thrombosis.     

Comparison of blood particle deposition models for non-parallel flow domains

Adhesions of monocytes and platelets to a vascular surface, particularly in regions of flow stagnation, recirculation, and reattachment, are a significant initial event in a broad spectrum of particle-wall interactions that significantly influence the formation of stenotic lesions and mural thrombi. A number of approximations are available for the simulation of both monocyte and platelet interactions with the vascular surface. For the simulation of blood particle adhesion, this study hypothesizes that: (a) the discrete element approach, which accounts for finite particle size and inertia, is advantageous in the context of non-parallel flow domains including stagnation, recirculation, and reattachment; and (b) the likelihood for particle deposition may be effectively approximated as being non-linearly proportional to local particle concentration, residence time, and wall proximity. Models such as wall shear stress correlations, the multicomponent mixture approach, and Lagrangian particle tracking with and without hydrodynamic particle-wall interactions were evaluated. Quantitative performance of the selected models was established by comparisons to available experimental data sets for non-parallel axisymmetric suspension flows of monocytes and platelets. Factors including the convective-diffusive transport of particles, finite particle size and inertia, as well as near-wall hydrodynamic interactions were found to significantly influence blood particle deposition. Of the models studied, the near-wall residence time approach was found to be a particularly effective indicator for the deposition of monocytes (r2=0.74) and platelets (r2=0.57), given that nano-scale physical and biochemical effects must be greatly approximated in computational simulations involving relatively large-scale geometries and complex flow fields.     

Hyperbolic symmetry breaking and its role in the establishment of the body plan of vertebrates

This Note presents experimental evidence that a hyperbolic tissue flow plays an important role in the establishment of the organization plan of vertebrates. We have followed the development of chicken embryos from the gastrula stage up to the moment when the body plan is recognizable. We have found that establishment of this plan occurs in the presence of a uniform tissue flow which at all stages presents a hyperbolic pattern. The flow is bidirectional in the antero-posterior direction, with a fixed point (stagnation point of the flow) which is a point of zero speed in all directions, in the reference frame of the egg. This stagnation point of the flow is located at the level of the presumptive yolk stalk of the chicken (analogous to the mammal navel). On either sides (left and right) of the body, the flow is also bidirectional. The antero-posterior bidirectionality and the left-right bidirectionality result in splitting of the embryo into four domains with vortex-like flow, with partial mirror symmetry between the left/right halves and top/bottom ones. The center of symmetry is the stagnation point. The broken symmetry of the flow is up-scaled in the adult animal. Areas with straightforward tissue movement are the ones where axial structures develop. The lateral domains with vortex-like flow colocalize with the future limb plates.     

Hemodynamic factors at the distal end-to-side anastomosis of a bypass graft with different POS:DOS flow ratios

A pulsatile flow in vitro model of the distal end-to-side anastomosis of an arterial bypass graft was used to examine the effects that different flow ratios between the proximal outlet segment (POS) and the distal outlet segment (DOS) have on the flow patterns and the distributions of hemodynamic factors in the anastomosis. Amberlite particles were tracked by flow visualization to determine overall flow patterns and velocity measurements were made with Laser Doppler anemometry (LDA) to obtain detailed hemodynamic factors along the artery floor and the graft hood regions. These factors included wall shear stress (WSS), spatial wall shear stress gradient (WSSG), and oscillatory index (OSI). Statistical analysis was used to compare these hemodynamic factors between cases having different POS:DOS flow ratios (Case 1-0:100, Case 2-25:75, Case 3-50:50). The results showed that changes in POS:DOS flow ratios had a great influence on the flow patterns in the anastomosis. With an increase in proximal outlet flow, the range of location of the stagnation point along the artery floor decreased, while the extent of flow separation along the graft hood increased. The statistical results showed that there were significant differences (p<0.05) for the mean WSS between cases along the graft hood, but no significant differences were detected along the artery floor. There were no significant differences for the spatial WSSG along both the artery floor and the graft hood. However, there were significant differences (p<0.05) in the mean OSI between Cases 1 and 2 and between Cases 1 and 3 both along the artery floor and along the graft hood. Comparing these mechanical factors with histological findings of intimal hyperplasia formation obtained by previous canine studies, the results of the statistical analysis suggest that regions exposed to a combination of low mean WSS and high OSI may be most prone to the formation of intimal hyperplasia.     

Microfluidic accumulation assay probes attachment of biofilm forming diatom cells

Testing of fouling release (FR) technologies is of great relevance for discovery of the next generation of protective marine coatings. In this paper, an accumulation assay to test diatom interaction under laminar flow with the model organism Navicula perminuta is introduced. Using time lapse microscopy with large area sampling allows determination of the accumulation kinetics of the diatom on three model surfaces with different surface properties at different wall shear stresses. The hydrodynamic conditions within the flow cell are described and a suitable shear stress range to perform accumulation experiments is identified at which statistically significant discrimination of surfaces is possible. The observed trends compare well to published adhesion preferences of N. perminuta. Also, previously determined trends of critical wall shear stresses required for cell removal from the same set of functionalized interfaces shows consistent trends. Initial attachment mediated by extracellular polymeric substances (EPS) present outside the diatoms leads to the conclusion that the FR potential of the tested coating candidates can be deducted from dynamic accumulation experiments under well-defined hydrodynamic conditions. As well as testing new coating candidates for their FR properties, monitoring of the adhesion process under flow provides additional information on the mechanism and geometry of attachment and the population kinetics.     

Role of blood cell-wall interactions in thrombogenesis and atherogenesis: a microrheological study

The relationship between blood flow and the localization of thrombosis and atherosclerosis in vivo was investigated using the approach and techniques of microrheology. The flow patterns and wall-adhesion of platelets were studied in the captive annular vortex formed at a sudden tubular expansion at various hematocrits in steady and pulsatile flow. The adhesion density exhibited a peak within the vortex and just downstream of the reattachment point, which is also a stagnation point. The peaks flattened out with increasing Reynolds number in steady flow and also in pulsatile flow. Platelet adhesion increased markedly with increasing hematocrit. The localization of adhesion peaks was explained by curvature of the streamlines carrying platelets to the wall on either side of the reattachment point. The relevance of these results to the circulation is that stagnation points are found in regions of disturbed flow at various sites in the arterial and venous circulations. This was shown in experiments using a technique whereby flow was visualized in isolated transparent natural blood vessels prepared from dogs and humans postmortem. In dog saphenous vein bileaflet valves, there was a large primary spiral vortex as well as a smaller secondary vortex, the latter acting as a trap and generator of thrombi. Recirculation zones also existed in the dog aorta at T-junctions of the celiac, cranial mesenteric and renal arteries. Finally, in the human carotid bifurcation, a large standing recirculation zone consisting of spiral secondary flows formed in the carotid sinus at physiological flow conditions.(ABSTRACT TRUNCATED AT 250 WORDS)