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)     

Vortex generation in pulsatile flow through arterial bifurcation models including the human carotid artery

Visualization experiments were performed to elucidate the complicated flow pattern in pulsatile flow through arterial bifurcations. Human common carotid arteries, which were made transparent, and glass-models simulating Y- and T-shaped bifurcations were used. Pulsatile flow with wave forms similar to those of arterial flow was generated with a piston pump, elastic tube, airchamber, and valves controlling the outflow resistance. Helically recirculating flow with a pattern similar to that of the horseshoe vortex produced around wall-based protuberances in circular tubes was observed in pulsatile flow through all the bifurcations used in the present study. This flow type, which we shall refer to as the horseshoe vortex, has also been demonstrated to occur at the human common carotid bifurcation in steady flow with Reynolds numbers above 100. Time-varying flows also produced the horseshoe vortex mostly during the decelerating phase. Fluid particles of dye solution approaching the bifurcation apex diverged, divided into two directions perpendicularly, and then showed helical motion representing the horseshoe vortex formation. While this helical flow was produced, the stagnation points appeared on the wall upstream of the apex. Their position was dependent upon the flow distribution ratio between the branches in the individual arteries. The region affected by the horseshoe vortex was smaller during pulsatile flow than during steady flow. Lowering the Reynolds number together with the Womersley number weakened the intensity of helical flow. A separation bubble, resulting from the divergence or wall roughness, was observed at the outer or inner wall of the branch vessels and made the flow more complicated.     

Visualization and finite element analysis of pulsatile flow in models of the abdominal aortic aneurysm

Pulsatile flows in glass models simulating fusiform and lateral saccular aneurysms were investigated by a flow visualization method. When resting fluid starts to flow, the initial fluid motion is practically irrotational. After a short period of time, the flow began to separate from the proximal wall of the aneurysm. Then the separation bubble or vortex grew rapidly in size and filled the whole area of the aneurysm circumferentially. During this period of time, the center of the vortex moved from the proximal end to the distal point of the aneurysm. The transient reversal flow, for instance, which may occur at the end of the ejection period, passed between the wall of the aneurysm and the centrally located vortex. When the rate and pulsatile frequency of flow were high, the vortex broke down into highly disturbed flow (or turbulence) at the distal portion of the aneurysm. The same effect was observed when the length of the aneurysm was increased. A reduction in pulsatile amplitude made the flow pattern close to that in steady flow. A finite element analysis was made to obtain velocity and pressure fields in pulsatile flow through a tube with an axisymmetric expansion. Calculations were performed with the pulsatile flows used in the visualization experiment in order to study the effects of change in the pulsatile wave form by keeping the time-mean Reynolds number and Womersley's parameter unchanged. Calculated instantaneous patterns of velocity field and stream lines agreed well with the experimental results. The appearance and disappearance of the vortex in the dilated portion and its development resulted in complex distributions of pressure and shear fields. Locally minimum and maximum values of wall shear stress occurred at points just upstream and downstream of the distal end of the expansion when the flow rate reached its peak.     

Numerical analysis of flow through a severely stenotic carotid artery bifurcation

The results of computational simulations may supplement MR and other in vivo diagnostic techniques to provide an accurate picture of the hemodynamics in particular vessels, which may help demonstrate the risks of embolism or plaque rupture posed by particular plaque deposits. In this study, a model based on an endarterectomy specimen of the plaque in a carotid bifurcation was examined. The flow conditions include steady flow at Reynolds numbers of 300, 600, and 900 as well as unsteady pulsatile flow. Both dynamic pressure and wall shear stress are very high, with shear values up to 70 N/m2, proximal to the stenosis throat in the internal carotid artery, and both vary significantly through the flow cycle. The wall shear stress gradient is also strong along the throat. Vortex shedding is observed downstream of the most severe occlusion. Two turbulence models, the Chien and Goldberg varieties of k-epsilon, are tested and evaluated for their relevance in this geometry. The Chien model better captures phenomena such as vortex shedding. The flow distal to stenosis is likely transitional, so a model that captures both laminar and turbulent behavior is needed.     

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.     

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.     

Stability of pulsatile blood flow at the ostium of cerebral aneurysms

The strength and direction of blood flow into and within a cerebral aneurysm are important issues in developing effective interventional strategies to stabilize the aneurysm. We tested the hypothesis that there are significant major hemodynamic features that are common to many aneurysm flows of the type studied here. This was investigated by performing computational fluid dynamic simulations of flow near 7 cerebral aneurysms using geometrical data obtained from clinical CT scans. Our numerical simulations of flow across the ostium plane of an aneurysm show that in many cases there is relatively stable flow structure that is maintained over the phase of the pulsatile flow cycle. The two main features of this flow are (1) quasi-permanent regions of flow influx and efflux across the ostium plane exist, separated by a “virtual boundary”, and (2) a helical vortex flow pattern within the aneurismal sac with swirl in two orthogonal cross-sectional planes. These numerical observations are consistent with in vitro experimental data from ultrasound color-Doppler velocimetry and other numerical and experimental studies. The observed flow patterns are found to occur in different types of aneurysms (bifurcation and sidewall), and can persist even after flow parameters are perturbed beyond the normal range of physiological flow conditions. These results suggest that in many cases, major aspects of the behavior of aneurismal hemodynamics for important classes of aneurysms can be learned from an analysis of steady, non-pulsatile flow, which is simpler and faster to simulate than time-dependent, pulsatile flow. An understanding of this fluid dynamical behavior may also prove useful in the design of stents, coils, and various other endovascular flow diverting devices.     

Numerical investigation of the non-Newtonian pulsatile blood flow in a bifurcation model with a non-planar branch

The pulsatile flow of non-Newtonian fluid in a bifurcation model with a non-planar daughter branch is investigated numerically by using the Carreau-Yasuda model to take into account the shear thinning behavior of the analog blood fluid. The objective of this study is to deal with the influence of the non-Newtonian property of fluid and of out-of-plane curvature in the non-planar daughter vessel on wall shear stress (WSS), oscillatory shear index (OSI), and flow phenomena during the pulse cycle. The non-Newtonian property in the daughter vessels induces a flattened axial velocity profile due to its shear thinning behavior. The non-planarity deflects flow from the inner wall of the vessel to the outer wall and changes the distribution of WSS along the vessel, in particular in systole phase. Downstream of the bifurcation, the velocity profiles are shifted toward the flow divider, and low WSS and high shear stress temporal oscillations characterized by OSI occur on the outer wall region of the daughter vessels close to the bifurcation. Secondary motions become stronger with the addition of the out-of-plane curvature induced by the bending of the vessel, and the secondary flow patterns swirl along the non-planar daughter vessel. A significant difference between the non-Newtonian and the Newtonian pulsatile flow is revealed during the pulse cycle; however, reasonable agreement between the non-Newtonian and the rescaled Newtonian flow is found. Calculated results for the pulsatile flow support the view that the non-planarity of blood vessels and the non-Newtonian properties of blood are an important factor in hemodynamics and may play a significant role in vascular biology and pathophysiology.     

Structure of pulsatile flow in a model of elastic cerebral aneurysm

This study examines the effect of aneurysmal wall elasticity on the structure of flow within an elastic aneurysm during pulsatile flow. We visualized flow structure in a model of an elastic saccular aneurysm located at the bifurcation of the anterior cerebral artery and extending to the anterior communicating artery, and measured changes in the diameter of the aneurysm wall during pulsatile flow using particle imaging velocimetry (PIV). We similarly measured these features during steady flow by PIV and found that dilation of the aneurysmal wall absorbed the dynamic energy within the aneurysm. Accordingly, aneurysm wall elasticity functions as a biocompatible reaction that relieves wall shear stress acting on the vascular wall during pulsatile flow, and should thus inhibit the development and rupture of an aneurysm.     

An LDA and flow visualization study of pulsatile flow in an aortic bifurcation model

The structure of pulsatile flow in a rigid aortic bifurcation model was studied by means of a flow visualization technique and three-dimensional laser-Doppler anemometry. The model was made of glass, having the same shape as that of the average human aortic bifurcation. It was installed into a mock circulatory loop that generated physiological pulsatile flow. Flow separation was observed during accelerated and decelerated flow periods. Double helical flow existed inside the flow separation in the early accelerated flow period. In the decelerated flow period, disturbed flow appeared behind the separation zone. Flow was strongly disturbed during the back flow period, and then was gradually stabilized in the forward flow period. The flow separation and the disturbances released from the flow separation zone greatly influenced near-wall velocities along the lateral wall. The wave form of the near-wall velocity in the flow separation zone was much different from that observed in the aortic portion and behind the separation zone; for example, the magnitude of the negative peak velocity in the direction of the tube axis was larger than that of the positive one, and mean velocity in a cycle was very low. This abnormal phasic change of the near-wall velocity may be associated with atherogenesis. The three-dimensional velocity measurement is very useful for the detailed analysis of near-wall velocity patterns.     

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.     

Blood flow and vessel mechanics in a physiologically realistic model of a human carotid arterial bifurcation

The pulsatile flow in an anatomically realistic compliant human carotid bifurcation was simulated numerically. Pressure and mass flow waveforms in the carotid arteries were obtained from an individual subject using non-invasive techniques. The geometry of the computational model was reconstructed from magnetic resonance angiograms. Maps of time-average wall shear stress, contours of velocity in the flow field as well as wall movement and tensile stress on the arterial wall are all presented. Inconsistent with previous findings from idealised geometry models, flow in the carotid sinus is dominated by a strong helical flow accompanied by a single secondary vortex motion. This type of flow is induced primarily by the asymmetry and curvature of the in vivo geometry. Flow simulations have been carried out under the rigid wall assumption and for the compliant wall, respectively. Comparison of the results demonstrates the quantitative influence of the vessel wall motion. Generally there is a reduction in the magnitude of wall shear stress, with its degree depending on location and phase of the cardiac cycle. The region of slow or reversed flow was greater, in both spatial and temporal terms in the compliant model, but the global characteristics of the flow and stress patterns remain unchanged. The analysis of mechanical stresses on the vessel surface shows a complicated stress field. Stress concentration occurs at both the anterior and posterior aspects of the proximal internal bulb. These are also regions of low wall shear stress. The comparison of computed and measured wall movement generally shows good agreement.     

Nonquasi-steady character of pulsatile flow in human coronary arteries

This experiment was conducted to determine if the pulsatile flow through the proximal portion of the left coronary artery system in man exhibits quasi-steady characteristics. Steady and pulsatile flows were passed through an idealized model whose dimensions were based on a vascular cast. The mean Reynolds number was 180 and the unsteadiness number was 2.7. Velocity profiles were measured by laser Doppler anemometry at several locations along diameters in the parent and both daughter channels in the neighborhood of the "left main" bifurcation. Analysis of the results along one diameter in the "left main" channel shows that unsteady flow in the larger coronary arteries may not be simulated by a series of steady flow experiments.     

Sequential venous anastomosis design to enhance patency of arterio-venous grafts for hemodialysis

Arterio-venous grafts (AVGs), the second best option as long-term vascular access for hemodialysis, face major issues of stenosis mainly due to development of intimal hyperplasia at the venous anastomosis which is linked to unfavorable hemodynamic conditions. We have investigated computationally the utility of a coupled sequential venous anastomotic design to replace conventional end-to-side (ETS) venous anastomosis, in order to improve the hemodynamic environment and consequently enhance the patency of AVGs. Two complete vascular access models with the conventional and the proposed venous anastomosis configurations were constructed. Three-dimensional, pulsatile blood flow through the models was simulated, and wall shear stress (WSS)-based hemodynamic parameters were calculated and compared between the two models. Simulation results demonstrated that the proposed anastomotic design provides: (i) a more uniform and smooth flow at the ETS anastomosis, without flow impingement and stagnation point on the artery bed and vortex formation in the heel region of the ETS anastomosis; (ii) more uniform distribution of WSS and substantially lower WSS gradients on the venous wall; and (iii) a spare route for the blood flow to the vein, to avoid re-operation in case of stenosis. The distinctive hemodynamic advantages observed in the proposed anastomotic design can enhance the patency of AVGs.     

Pulsatile non-Newtonian blood flow simulation through a bifurcation with an aneurysm

Blood flow is analysed by means of computer simulation in an idealized arterial bifurcation model which is pathologically altered by a saccular aneurysm. The theoretical study of the flow pattern and the paths of fluid particles is carried out under pulsatile Newtonian and non-Newtonian flow conditions. The governing equations are solved numerically with the use of the finite element method. The results show the disturbed blood flow in the bifurcation and the relatively low intra-aneurysmal flow circulation. In addition to the study of basic flow patterns in the segment, a comparison of non-Newtonian and Newtonian results is carried out. This comparison proves that for the considered large artery model under physiological flow conditions where the yield number is relatively low there is no essential difference in the results.     

Blood flow multiscale phenomena

The cardiovascular disease is one of most frequent cause deaths in modern society. The objective of this work is analyse the effect of dynamic vascular geometry (curvature, torsion, bifurcation) and pulsatile blood nature on secondary flow, wall shear stress and platelet deposition. The problem was examined as multi-scale physical phenomena using perturbation analysis and numerical modelling. The secondary flow determined as influence pulsatile pressure, vascular tube time-dependent bending and torsion on the main axial flow. Bifurcation and branching phenomena are analysed experimentally through, blood-like fluid pulsatile flow across elastic rubber-like Y-model model. The problem complex geometry near branching in platelet deposit modelling is resolved numerically as Falker-Skan flow.     

Pulsatile flow in a constricted channel.

A nonuniform channel is used as a simple model of a constricted arterial vessel. Flow patterns have been calculated for pulsatile flow with both sinusoidal and nonsinusoidal flow rates for a range of Reynolds number, Re, and Strouhal number, St. The results show that even for relatively low frequency flows a strong vortex wave will be generated with a complex wall shear stress distribution and peak values much greater than those found in steady or unsteady parallel flow. The vortex wave increases in strength with increasing Re and St, with its total length and wavelength independent of Re but inversely proportional to St. The form of the imposed flow rate is found to have an important effect on the flow and the shear stress distribution.     

Turbulence detection in a stenosed artery bifurcation by numerical simulation of pulsatile blood flow using the low-Reynolds number turbulence model

The pulsatile blood flow in a partially blocked artery is significantly altered as the flow regime changes through the cardiac cycle. This paper reports on the application of a low-Reynolds turbulence model for computation of physiological pulsatile flow in a healthy and stenosed carotid artery bifurcation. The human carotid artery was chosen since it has received much attention because atherosclerotic lesions are frequently observed. The Wilcox low-Re k-omega turbulence model was used for the simulation since it has proven to be more accurate in describing transition from laminar to turbulent flow. Using the FIDAP finite element code a validation showed very good agreement between experimental and numerical results for a steady laminar to turbulent flow transition as reported in a previous publication by the same authors. Since no experimental or numerical results were available in the literature for a pulsatile and turbulent flow regime, a comparison between laminar and low-Re turbulent calculations was made to further validate the turbulence model. The results of this study showed a very good agreement for velocity profiles and wall shear stress values for this imposed pulsatile laminar flow regime. To explore further the medical aspect, the calculations showed that even in a healthy or non-stenosed artery, small instabilities could be found at least for a portion of the pulse cycle and in different sections. The 40% and 55% diameter reduction stenoses did not significantly change the turbulence characteristics. Further results showed that the presence of 75% stenoses changed the flow properties from laminar to turbulent flow for a good portion of the cardiac pulse. A full 3D simulation with this low-Re-turbulence model, coupled with Doppler ultrasound, can play a significant role in assessing the degree of stenosis for cardiac patients with mild conditions.     

Comparison of steady and pulsatile flow near the ventral and dorsal walls of casts of human aortic bifurcations

Steady and pulsatile flows were passed through casts of human aortic bifurcations and, by means of a laser Doppler anemometer, fluid velocities were measured at selected sites near the ventral and dorsal walls. At these sites, in the vicinity of the bifurcation, the influence of secondary flow is significant and therefore an appreciation of the phasic variation of secondary flow patterns is important. Results are presented comparing the flow direction in both steady and pulsatile flow at sites in three casts. The common features of the flow at these sites were the persistence of the flow direction during the accelerating and decelerating phases of the pulsatile cycle, and the consistently smaller angle (measured from the inlet centerline) of the pulsatile flow direction as compared to the angle of the flow direction in steady flow.     

Determination of volume of vortices in poststenotic pulsatile flow by ultrasonic Doppler power ratio and spectrum analysis

Based on the principle of ultrasonic Doppler flowmetry, a power ratio was derived from independent forward and reverse flow Doppler shift signals to measure a ratio of the volume of vortices to the total vessel volume in poststenotic separated flow. The ratio was also proportional to the ratio of the cross-sectional areas of vortices to the vessel lumen. In vitro pulsatile flow experiments were performed to test the methodology and to study flow separation and vortex shedding downstream from model stenoses. The averaged flow cross-sectional area ratio linearly correlated (r = 0.91) with the actual area reduction of the stenosis.