Lipid deposition and intimal stress and strain. A study in rats with aortic stenosis.

These experiments were designed to study the topography of lipid deposition in the stenotic aorta of hypercholesterolemic rats, and to correlate it with flow conditions and intimal stresses and strains studied in a scale biophysical model and in a computer model. A 69% +/- 5% stenosis was produced with a U-shaped metal clip. One month to 8 months later, the aorta was studied en face by light microscopy after fixation and lipid staining. The intima in the throat of the stenosis was almost completely free of lipid, whereas symmetric lipid deposits occurred as bands just above and especially just below the stenosis; elsewhere lipid deposits appeared to be random. The flow data obtained from the scale model showed that the intima in the throat of the stenosis was subjected to an increase of as much as 20 times in shear stress, whereas the lipid deposits just above and just below the stenosis were associated with asymmetric flow conditions: the proximal area corresponded to a region of rapidly increasing shear stress, the distal area to a region of low to normal shear stress and separated flow. A finite element computer model based on the aortic deformations indicated that the endothelium at the inlet and outlet of the stenosis is subjected to a symmetric pattern of elevated stresses and strains. These results indicate that 1) the pattern of lipid deposition can not be adequately explained by a hypothesis based solely on flow conditions, and 2) lipid deposits can develop in areas of increased fluid shear stress, decreased fluid shear stress, and increased intimal strains.     

Effect of magnetic field on haemodynamic perturbations in atherosclerotic coronary arteries

Haemodynamic perturbations including elevated blood viscosity, low and oscillatory shear stress are understood to be important pathogenic mediators in atherosclerosis. These haemodynamic abnormalities are influenced by the presence of a magnetic field. This study conducted computational fluid dynamics (CFD) analysis in 4 coronary artery models, derived from authentic human coronaries, with mild and moderate and severe stenosis severity. The aim was to investigate the effect of a static magnetic field of varying intensities on blood viscosity, areas of low wall shear stress (ALWSS), maximum wall shear stress (MWSS) and length and volume of flow recirculation zones. The results showed that the magnetic field results in both beneficial and detrimental changes in haemodynamics. The beneficial effects are lowered viscosity, decreased size of ALWSS and flow recirculation zones whereas the detrimental effect is increased MWSS. With increasing stenosis severity the effect of magnetic field becomes more prominent. An externally applied magnetic field can improve haemodynamics perturbations in human coronary arteries, especially in the setting of moderate-to-severe stenosis severity.     

Finite Element Modeling of Three-Dimensional Pulsatile Flow in the Abdominal Aorta: Relevance to Atherosclerosis

The infrarenal abdominal aorta is particularly prone to atherosclerotic plaque formation while the thoracic aorta is relatively resistant. Localized differences in hemodynamic conditions, including differences in velocity profiles, wall shear stress, and recirculation zones have been implicated in the differential localization of disease in the infrarenal aorta. A comprehensive computational framework was developed, utilizing a stabilized, time accurate, finite element method, to solve the equations governing blood flow in a model of a normal human abdominal aorta under simulated rest, pulsatile, flow conditions. Flow patterns and wall shear stress were computed. A recirculation zone was observed to form along the posterior wall of the infrarenal aorta. Low time-averaged wall shear stress and high shear stress temporal oscillations, as measured by an oscillatory shear index, were present in this location, along the posterior wall opposite the superior mesenteric artery and along the anterior wall between the superior and inferior mesenteric arteries. These regions were noted to coincide with a high probability-of-occurrence of sudanophilic lesions as reported by Cornhill et al. (Monogr. Atheroscler. 15:13--19, 1990). This numerical investigation provides detailed quantitative data on hemodynamic conditions in the abdominal aorta heretofore lacking in the study of the localization of atherosclerotic disease. © 1998 Biomedical Engineering Society. PAC98: 8745Hw, 0270Dh, 8710+e     

Application of the lattice Boltzmann model to simulated stenosis growth in a two-dimensional carotid artery

The lattice Boltzmann model is used to observe changes in the velocity flow and shear stress in a carotid artery model during a simulated stenosis growth. Near wall shear stress in the unstenosed artery is found to agree with literature values. The model also shows regions of low velocity, rotational flow and low near wall shear stress along parts of the walls of the carotid artery that have been identified as being prone to atherosclerosis. These regions persist during the simulated stenosis growth, suggesting that atherosclerotic plaque build-up creates regions of flow with properties that favour atherosclerotic progression.     

Hemodynamics analyses of arterial expansions with implications to thrombosis and restenosis

It is assumed that critical hemodynamic factors play an important role in the onset, localization and degree of post-operative complications, for example, thrombosis and restenosis. Of special interest are sudden expansion flows, which may occur in straight artery segments such as the common carotid after endarterectomy or end-to-end anastomoses. Sudden expansion geometries are possible origins of early post-operative emboli and significant myointimal hyperplasia resulting in early or late complications. Transient laminar axisymmetric and fully three-dimensional blood flows were simulated employing a validated finite volume code in conjunction with a Runge-Kutta particle tracking technique. Disturbed flow indicators, which may predict the onset of thrombosis and/or restenosis, were identified and employed to evaluate 90 degrees -step and smooth expansion geometries.Smooth expansion geometries have weaker disturbed flow features than step expansion geometries. Specifically, the regions near the expansion wall and the reattachment point are susceptible to both atherosclerotic lesion and thrombi formations as indicated by non-uniform hemodynamic indicators such as near-zero wall shear stress and elevated wall shear stress gradients as well as blood particle accumulation and deposition. A new parameter, the wall shear stress angle deviation (WSSAD) has been introduced, which indicates areas of abnormal endothelial cell morphology and particle wall deposition. In turn, regions of low wall shear stress and high wall shear stress gradients are recognized as susceptible sites for arterial diseases. Thus, it is interesting to note that high WSSAD surface areas cover low wall shear stress, high wall shear stress gradient locations as well as high wall particle deposition.A gradual change in step expansion geometry provides better results in terms of WSSAD values and hence potentially reducing atherosclerosis as well as thrombi formation.     

Fluid mechanics of arterial stenosis: Relationship to the development of mural thrombus

In this study, we analyzed blood flow through a model stenosis with Reynolds numbers ranging from 300 to 3,600 using both experimental and numerical methods. The jet produced at the throat was turbulent, leading to an axisymmetric region of slowly recirculating flow. For higher Reynolds numbers, this region became more disturbed and its length was reduced. The numerical predictions were confirmed by digital particle image velocimetry and used to describe the fluid dynamics mechanisms relevant to prior measurements of platelet deposition in canine blood flow (R.T. Schoephoersteret al., Atherosclerosis and Thrombosis 12:1806–1813, 1993). Actual deposition onto the wall was dependent on the wall shear stress distribution along the stenosis, increasing in areas of flow recirculation and reattachment. Platelet activation potential was analyzed under laminar and turbulent flow conditions in terms of the cumulative effect of the varying shear and elongational stresses, and the duration platelets are exposed to them along individual platelet paths. The cumulative product of shear rate and exposure time along a platelet path reached a value of 500, half the value needed for platelet activation under constant shear (J. M. Ramstacket al., Journal of Biomechanics 12: 113–125, 1979).     

Theoretical study of the effect of local flow disturbances on the concentration of low-density lipoproteins at the luminal surface of end-to-end anastomosed vessels

To elucidate the mechanisms of localisation of intimal hyperplasia in anastomosed arteries, the effects of flow disturbances on the transport of lowdensity lipoproteins (LDLs) from the flowing blood to the wall of end-to-end anastomosed arteries, with and without a moderate stenosis, were studied theoretically by means of a computer simulation under the condition of steady flow. In an artery with moderate stenosis at the anastomotic junction and intimal thickening distal to it, we found that, owing to the water-permeable nature of the arterial wall, the surface concentration of LDL was elevated up to 20% higher than that of the bulk flow distal to the stenosis, where a recirculation zone was formed and wall shear stresses were low. In contrast to this, no significant elevation of surface concentration of LDLs occurred in another anastomosed vessel in which no stenosis was formed and no intimal thickening was observed. These results suggest that flowdependent concentration polarisation of LDLs plays a causative role in the localisation of anastomotic intimal hyperplasia in the human arterial system by locally elevating the surface concentration of LDLs, thus augmenting their uptake by endothelial cells.     

A numerical and experimental study of periodic flow in a model of a corrugated vessel with application to stented arteries

The investigation presented in this paper has attempted to study, from a fluid dynamics point of view, the consequences of the presence of a stent on the flow of blood. The method adopted is mainly by numerical simulation using a finite element technique, but visualization experiments and an analytical study have also been carried out. The flow of blood is treated as being transient, laminar and Newtonian within a rigid section of the stented vessel. The flow is driven by an imposed pressure gradient in the form of a physiological waveform. A periodic boundary condition has been applied. Particle trajectories, fluid shear rate contours and wall shear stress maps, together with the use of a simplified form of particle image velocimetry in the experimental work, have been used to interpret the results. It was found that the vessel wall experienced oscillating levels of wall shear stress, in particular extensive exposure to low shear stress. Regions of flow recirculation, points of flow separation and reattachment constantly move in regions of low shear stress. Vortices form and then are destroyed rapidly by reversing flow. Their potential physiological significance to stented arteries is discussed.     

兔腹主动脉狭窄后剪切力的变化对局部内皮细胞形态和通透性的影响

兔腹主动脉狭窄至正常的55.2％，伊文思蓝对动脉染色，在扫描电镜下观察内皮细胞形态，计算细胞形态指数。动脉狭窄血管内流动壁面剪切率的分布由计算机数值模拟确定。结果表明，在紧接狭窄处的近远两侧，血流受到严重干扰，内皮细胞的形态和对伊文思蓝白蛋白复合物通透性发生明显改变。研究表明，这些改变不但与剪切应力的大小有关，还与血液流动的状态有关。这与动脉粥样硬化一般好发于血液流动受到干扰，流动发生分离区域的解剖观察一致。     

Can eccentric arterial plaques alone cause flow stagnation points and favour thrombus incorporation?

We have used an experimental model of aorta stenosis, with a Plexiglas plug, simulating a stable atheromatous plaque that promotes local turbulence and thrombosis. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 30 days. The mushroom plug form permitted the development of recirculation and stasis areas around it, favouring this evolution. Despite noted limitations, this study demonstrates that thrombus incorporation can contribute to plaque extension, as it can promote recirculation and stasis areas.     

Circumferential wall tension due to hypertension plays a pivotal role in aorta remodelling

The present study was carried out to investigate the role of hypertension in the genesis and localization of intimal lesions and medial remodelling found in the prestenotic segment in relation to a severe stenosis of the abdominal aorta just below the diaphragm. Male young rats were divided randomly into operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Aortas in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress were characterized by enlarged heterogeneous endothelial cells elongated in the direction of the blood flow, diffusely distributed conspicuous neointimal plaques and medial thickening. The immunohistochemical analysis revealed an increased expression of eNOS, iNOS, nitrotyrosine and transforming growth factor-beta (TGF-beta) in endothelial cells and/or smooth muscle cells in this segment. Our findings suggest that increased circumferential wall tension due to hypertension plays a pivotal role in the remodelling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-beta expression. Further studies are needed to clarify the intrinsic pathogenetic mechanism of focal distribution of the neointimal plaques in the hypertensive segment.     

Including aortic valve morphology in computational fluid dynamics simulations: Initial findings and application to aortic coarctation

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a post-surgical CoA patient (BAV). Velocity, turbulent kinetic energy (TKE), time-averaged wall shear stress (TAWSS), and oscillatory shear index (OSI) results were compared to equivalent simulations using a plug inlet profile. The plug inlet greatly underestimated TKE for both examples. TAWSS differences extended throughout the thoracic aorta for the CoA BAV, but were limited to the arch for the normal example. OSI differences existed mainly in the ascending aorta for both cases. The impact of AoV can now be included with CFD simulations to identify regions of deleterious hemodynamics thereby advancing simulations of the thoracic aorta one step closer to reality.     

Coupled fluid-wall modelling of steady flow in stenotic carotid arteries

Arterial stenoses may cause critical blood flow and wall conditions leading to clinical complications. In this paper computational models of stenotic carotid arteries are proposed and the vessel wall collapse phenomenon is studied. The models are based on fluid-structure interactions (FSI) between blood and the arterial walls. Coupled finite element and computational fluid dynamics methods are used to simultaneously solve for stress and displacement in the solid, and for pressure, velocity and shear stress in the fluid domain. Results show high wall shear stress at the stenosis throat and low (negative) values accompanied by disturbed flow patterns downstream of the stenosis. The wall circumferential stress varies abruptly from tensile to compressive along the stenosis with high stress concentration on the plaque shoulders showing regions of possible plaque rupture. Wall compression and collapse are observed for severe cases. Post-stenotic collapse of the arterial wall occurs for stenotic severity as low as 50%, with the assumption that a given amount of blood flow needs to pass the stenotic artery; whereas if constant pressure drop should be maintained across a constriction, then collapse happens at severity of 75% and above. The former assumption is based on the requirement of adequate blood supply to the downstream organs/tissue, while the latter stems from the fact that the pumping mechanism of the body has a limited capacity in regulating blood pressure, in case a stenosis appears in the vasculature.     

The Flow Field along the Entire Length of Mouse Aorta and Primary Branches

There is a spatial disposition to atherosclerosis along the aorta corresponding to regions of flow disturbances. The objective of the present study is to investigate the detailed distribution of hemodynamic parameters (wall shear stress (WSS), spatial gradient of wall shear stress (WSSG), and oscillatory shear index (OSI)) in the entire length of C57BL/6 mouse aorta with all primary branches (from ascending aorta to common iliac bifurcation). The detailed geometrical parameters (e.g., diameter and length of the vessels) were obtained from casts of entire aorta and primary branches of mice. The flow velocity was measured at the inlet of ascending aorta using Doppler flowprobe in mice. The outlet pressure boundary condition was estimated based on scaling law. The continuity and Navier–Stokes equations were solved using three-dimensional finite element method (FEM). The model prediction was tested by comparing the computed flow rate with the flow rate measured just before the common iliac bifurcation, and good agreement was found. It was also found that complex flow patterns occur at bifurcations between main trunk and branches. The major branches of terminal aorta, with the highest proportion of atherosclerosis, have the lowest WSS, and the relatively atherosclerotic-prone aortic arch has much more complex WSS distribution and higher OSI value than other sites. The low WSS coincides with the high OSI, which approximately obeys a power law relationship. Furthermore, the scaling law between flow and diameter holds in the entire aorta and primary branches of mice under pulsatile blood flow conditions. This model will eventually serve to elucidate the causal relation between hemodynamic patterns and atherogenesis in KO mice.     

A Follow-up MRI-based Geometry and Computational Fluid Dynamics Study of Carotid Bifurcation

Cardiovascular disease is the leading causes of death in the developed world. Wall shear stress(WSS) is associated with the initiation and progression of atherogenesis. This study combined the recent advances in MR imaging and computational fluid dynanucs(CFD) and evaluated the patient-specific carotid bifurcation. The patient was followed up for 3 years. The geometry changes(tortuosity,curvature, ICA/CCA area ratios, central to the cross-sectional curvature, maximum stenosis) and the CFD factors(velocity distribute, wall shear stress(WSS) and oscillatory shear index(OSI) were compared at different time points.The carotid stenosis was a slight increase in the central to the cross-sectional curvature, and it was minor and variable curvature changes for carotid centerline. The OSI distribution presents a high-values in the same region where carotid stenosis and normal border,indicating complex flow and recirculation.The significant geometric changes observed during the follow-up may also cause significant changes in bifurcation hemodynamics.     

On the Characterization of a Non-Newtonian Blood Analog and Its Response to Pulsatile Flow Downstream of a Simplified Stenosis

Particle image velocimetry (PIV) was used to investigate the influence of a non-Newtonian blood analog of aqueous xanthan gum on flow separation in laminar and transitional environments and in both steady and pulsatile flow. Initial steady pressure drop measurements in laminar and transitional flow for a Newtonian analog showed an extension of laminar behavior to Reynolds number (Re) ~ 2900 for the non-Newtonian case. On a macroscale level, this showed good agreement with porcine blood. Subsequently, PIV was used to measure flow patterns and turbulent statistics downstream of an axisymmetric stenosis in the aqueous xanthan gum solution and for a Newtonian analog at Re ~ 520 and Re ~ 1250. The recirculation length for the non-Newtonian case was reduced at Re ~ 520 resultant from increased viscosity at low shear strain rates. At Re ~ 1250, peak turbulent intensities and turbulent shear stresses were dampened by the non-Newtonian fluid in close proximity to the blockage outlet. Although the non-Newtonian case’s recirculation length was increased at peak pulsatile flow, turbulent shear stress was found to be elevated for the Newtonian case downstream from the blockage, suggesting shear layer fragmentation and radial transport. Our findings conclude that the xanthan gum elastic polymer prolongs flow stabilization, which in turn emphasizes the importance of non-Newtonian blood characteristics on the resulting flow patterns in such cardiovascular environments.     

Quantification of wall shear stress in large blood vessels using Lagrangian interpolation functions with cine phase-contrast magnetic resonance imaging

Arterial wall shear stress is hypothesized to be an important factor in the localization of atherosclerosis. Current methods to compute wall shear stress from magnetic resonance imaging (MRI) data do not account for flow profiles characteristic of pulsatile flow in noncircular vessel lumens. We describe a method to quantify wall shear stress in large blood vessels by differentiating velocity interpolation functions defined using cine phase-contrast MRI data on a band of elements in the neighborhood of the vessel wall. Validation was performed with software phantoms and an in vitro flow phantom. At an image resolution corresponding to in vivo imaging data of the human abdominal aorta, time-averaged, spatially averaged wall shear stress for steady and pulsatile flow were determined to be within 16% and 23% of the analytic solution, respectively. These errors were reduced to 5% and 8% with doubling in image resolution. For the pulsatile software phantom, the oscillation in shear stress was predicted to within 5%. The mean absolute error of circumferentially resolved shear stress for the nonaxisymmetric phantom decreased from 28% to 15% with a doubling in image resolution. The irregularly shaped phantom and in vitro investigation demonstrated convergence of the calculated values with increased image resolution. We quantified the shear stress at the supraceliac and infrarenal regions of a human abdominal aorta to be 3.4 and 2.3 dyn/cm², respectively. © 2002 Biomedical Engineering Society. PAC2002: 8761-c, 8719Uv     

Hemodynamics of the Normal Aorta Compared to Fusiform and Saccular Abdominal Aortic Aneurysms with Emphasis on a Potential Thrombus Formation Mechanism

Abdominal Aortic Aneurysms (AAAs), i.e., focal enlargements of the aorta in the abdomen are frequently observed in the elderly population and their rupture is highly mortal. An intra-luminal thrombus is found in nearly all aneurysms of clinically relevant size and multiply affects the underlying wall. However, from a biomechanical perspective thrombus development and its relation to aneurysm rupture is still not clearly understood. In order to explore the impact of blood flow on thrombus development, normal aortas (n = 4), fusiform AAAs (n = 3), and saccular AAAs (n = 2) were compared on the basis of unsteady Computational Fluid Dynamics simulations. To this end patient-specific luminal geometries were segmented from Computerized Tomography Angiography data and five full heart cycles using physiologically realistic boundary conditions were analyzed. Simulations were carried out with computational grids of about half a million finite volume elements and the Carreau–Yasuda model captured the non-Newtonian behavior of blood. In contrast to the normal aorta the flow in aneurysm was highly disturbed and, particularly right after the neck, flow separation involving regions of high streaming velocities and high shear stresses were observed. Naturally, at the expanded sites of the aneurysm average flow velocity and wall shear stress were much lower compared to normal aortas. These findings suggest platelets activation right after the neck, i.e., within zones of pronounced recirculation, and platelet adhesion, i.e., thrombus formation, downstream. This mechanism is supported by recirculation zones promoting the advection of activated platelets to the wall.     

Coupling of shear–circumferential stress pulses investigation through stress phase angle in FSI models of stenotic artery using experimental data

Many cardiovascular diseases are closely associated with hemodynamic parameters. The main purpose of this study is mimicking a physiological blood flow in stenotic arteries to provide an understanding of hemodynamic parameters. An experimental setup was designed to produce original pulsatile flow and measure pressure pulse waves through a compliant tube. Moreover, a numerical model considering fluid–solid interaction was developed to investigate wall shear stress and circumferential stress waves, based on the results of the experiments. Results described elevated mean pressure by increasing stenosis severity especially at the critical obstacle of 50 %, which the pressure rose significantly and raised up by 10 mm Hg that may cause damage in endothelial cells. Increasing in stenosis severity led to: more negative wall shear stress and more oscillation of shear stress at the post-stenotic region and also more absolute value of angular phase difference between wall shear stress and circumferential stress waves at the stenotic throat. All of the aforementioned parameters determinant the endothelial cell pathology in predication of potential sites of progression of atherosclerotic plaques. Therefore, results can be applied in study of plaque growth and mechanisms of arterial remodeling in atherosclerosis.     

Endothelial adaptations in aortic stenosis. Correlation with flow parameters.

A 69 +/- 5% stenosis was produced in the rat aorta, with the purpose of correlating endothelial changes with local flow patterns and with levels of shear stress; the hydrodynamic data were obtained from a scaled-up model of the stenosed aorta. In the throat of the stenosis, where shear stress values were 15-25 times normal, the endothelium was stripped off within 1 hour. It regenerated at half the rate of controls but modulated into a cell type that could withstand the increased shear stress. Adaptations included changes in cell orientation, number, length, width, thickness, stress fibers, and anchoring structures, as well as changes in the length, argyrophilia, and permeability of the junctions. Areas of either elongated or "polygonal" cells consistently developed at the same sites in relation to the stenosis, but the hydrodynamic data showed that they did not always correspond (as had been anticipated) to high and low shear, respectively. It is concluded that endothelial cell shape in the living artery must be determined by some other factor(s) in addition to shear stress.