Hemodynamics simulation and identification of susceptible sites of atherosclerotic lesion formation in a model abdominal aorta

Employing the rabbit's abdominal aorta as a suitable atherosclerotic model, transient three-dimensional blood flow simulations and monocyte deposition patterns were used to evaluate the following hypotheses: (i) simulation of monocyte transport through a model of the rabbit abdominal aorta yields cell deposition patterns similar to those seen in vivo, and (ii) those deposition patterns are correlated with hemodynamic wall parameters related to atherosclerosis. The deposition pattern traces a helical shape down the aorta with local elevation in monocyte adhesion around vessel branches. The cell deposition pattern was altered by an exercise waveform with fewer cells attaching in the upper abdominal aorta but more attaching around the renal orifices. Monocyte deposition was correlated with the wall shear stress gradient and the wall shear stress angle gradient. The wall stress gradient, the wall shear stress angle gradient and the normalized monocyte deposition fraction were correlated with the distribution of monocytes along the abdominal aorta and monocyte deposition is correlated with the measured distribution of monocytes around the major abdominal branches in the cholesterol-fed rabbit. These results suggest that the transport and deposition pattern of monocytes to arterial endothelium plays a significant role in the localization of lesions.     

A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms

In the circulation, flow-responsive endothelial cells (ECs) lining the lumen of blood vessels are continuously exposed to complex hemodynamic forces. To increase our understanding of EC response to these dynamic shearing forces, a novel in vitro flow model was developed to simulate pulsatile shear stress waveforms encountered by the endothelium in the arterial circulation. A modified waveform modeled after flow patterns in the human abdominal aorta was used to evaluate the biological responsiveness of human umbilical vein ECs to this new type of stimulus. Arterial pulsatile flow for 24 hours was compared to an equivalent time-average steady laminar shear stress, using no flow (static) culture conditions as a baseline. While both flow stimuli induced comparable changes in cell shape and alignment, distinct patterns of responses were observed in the distribution of actin stress fibers and vinculin-associated adhesion complexes, intrinsic migratory characteristics, and the expression of eNOS mRNA and protein. These results thus reveal a unique responsiveness of ECs to an arterial waveform and begin to elucidate the complex sensing capabilities of the endothelium to the dynamic characteristics of flows throughout the human vascular tree.     

Numerical study on the effect of secondary flow in the human aorta on local shear stresses in abdominal aortic branches

Flow in the aortic arch is characterized primarily by the presence of a strong secondary flow superimposed over the axial flow, skewed axial velocity profiles and diastolic flow reversals. A significant amount of helical flow has also been observed in the descending aorta of humans and in models. In this study a computational model of the abdominal aorta complete with two sets of outflow arteries was adapted for three-dimensional steady flow simulations. The flow through the model was predicted using the Navier-Stokes equations to study the effect that a rotational component of flow has on the general flow dynamics in this vascular segment. The helical velocity profile introduced at the inlet was developed from magnetic resonance velocity mappings taken from a plane transaxial to the aortic arch. Results showed that flow division ratios increased in the first set of branches and decreased in the second set with the addition of rotational flow. Shear stress varied in magnitude with the addition of rotational flow, but the shear stress distribution did not change. No regions of flow separation were observed in the iliac arteries for either case. Helical flow may have a stabilizing effect on the flow patterns in branches in general, as evidenced by the decreased difference in shear stress between the inner and outer walls in the iliac arteries.     

Modeling pulsatile flow in aortic aneurysms: effect of non-Newtonian properties of blood

Pulsatile flow in an axisymmetric rigid-walled model of an abdominal aorta aneurysm was analyzed numerically for various aneurysm dilations using physiologically realistic resting waveform at time-averaged Reynolds number of 300 and peak Reynolds number of 1607. Discretization of the governing equations was achieved using a finite element scheme based on the Galerkin method of weighted residuals. Comparisons with previously published work on the basis of special cases were performed and found to be in excellent agreement. Our findings indicate that the velocity fields are significantly affected by non-Newtonian properties in pathologically altered configurations. Non-Newtonian fluid shear stress is found to be greater than Newtonian fluid shear stress during peak systole. Further, the maximum shear stress is found to occur near the distal end of AAA during peak systole. The impact of non-Newtonian blood flow characteristics on pressure compared to Newtonian model is found insignificant under resting conditions. Viscous and inertial forces associated with blood flow are responsible for the changes in the wall that result in thrombus deposition and dilation while rupture of AAA is more likely determined by much larger mechanical stresses imposed by pulsatile pressure on the wall of AAA.     

Pulsatile flow visualization in the abdominal aorta under differing physiologic conditions: implications for increased susceptibility to atherosclerosis.

The infrarenal abdominal aorta is a common site for clinically significant atherosclerosis. As has been shown in other susceptible locations, vessel geometry, flow division rates, and pulsatility may result in hemodynamic conditions which influence the preferential localization of disease in the abdominal aorta segment. Pulsatile flow visualization was performed in a glass model of the aorta constructed from measurements of angiograms and cadaver aortas. Flow rates and pulsatile waveforms were varied to reflect typical physiological conditions. Under normal resting conditions, the flow patterns in the infrarenal aorta were more complex than those in the suprarenal location. Time varying vortex patterns appeared at the level of the renal arteries and propagated through the infrarenal aorta into the common iliac arteries. A region of oscillating velocity direction extended from the renal arteries to the aortic bifurcation along the posterior wall. Dye became trapped along the posterior wall, requiring several cardiac cycles for clearance. In contrast, there was rapid clearance of the dye in the anterior aorta. Under postprandial conditions, the flow patterns in the aorta were basically unchanged. Simulated exercise conditions created laminar hemodynamic features very different from the resting conditions, including a decrease in dye residence time. This study reveals significant time-dependent variations in the hemodynamics of the abdominal aorta under differing physiologic conditions. Hemodynamic factors such as low wall shear stress, oscillating shear direction, and high particle residence time may be related to the clinically seen preferential plaque localization in the infrarenal aorta.     

Different Long-Term Outcomes of Abdominal Aortic Aneurysm and Intracranial Aneurysm Models: Hemodynamic Change may also Play an Essential Role in the Initiation and Progression of Abdominal Aortic Aneurysm in Rabbits

Self-healing phenomenon was found in the periarterial elastase-induced abdominal aortic aneurysm (AAA) in rabbit. This kind of aneurysm model does not progress and heals spontaneously in the long term, which is quite different from the performance of AAA disease in human. In order to better mimic human AAA and overcome this shortcoming of traditional AAA model in rabbit, we studied the pathogenesis of cerebral aneurysm (CA) model in small animal, which shows an excellent long-term patency and progressive enlargement. We found that hemodynamic conditions, such as turbulence flow, high blood flow, and shear stress, play an important role in the formation and progression of CA. So, we hypothesize that hemodynamic change may also play an essential role in the initiation and progression of rabbit AAA, and self-healing will be overcome if hemodynamic condition changes by coarctation of infra-renal aorta after elastase incubation.     

Comparative study of viscoelastic arterial wall models in nonlinear one-dimensional finite element simulations of blood flow

It is well known that blood vessels exhibit viscoelastic properties, which are modeled in the literature with different mathematical forms and experimental bases. The wide range of existing viscoelastic wall models may produce significantly different blood flow, pressure, and vessel deformation solutions in cardiovascular simulations. In this paper, we present a novel comparative study of two different viscoelastic wall models in nonlinear one-dimensional (1D) simulations of blood flow. The viscoelastic models are from papers by Holenstein et al. in 1980 (model V1) and Valdez-Jasso et al. in 2009 (model V2). The static elastic or zero-frequency responses of both models are chosen to be identical. The nonlinear 1D blood flow equations incorporating wall viscoelasticity are solved using a space-time finite element method and the implementation is verified with the Method of Manufactured Solutions. Simulation results using models V1, V2 and the common static elastic model are compared in three application examples: (i) wave propagation study in an idealized vessel with reflection-free outflow boundary condition; (ii) carotid artery model with nonperiodic boundary conditions; and (iii) subject-specific abdominal aorta model under rest and simulated lower limb exercise conditions. In the wave propagation study the damping and wave speed were largest for model V2 and lowest for the elastic model. In the carotid and abdominal aorta studies the most significant differences between wall models were observed in the hysteresis (pressure-area) loops, which were larger for V2 than V1, indicating that V2 is a more dissipative model. The cross-sectional area oscillations over the cardiac cycle were smaller for the viscoelastic models compared to the elastic model. In the abdominal aorta study, differences between constitutive models were more pronounced under exercise conditions than at rest. Inlet pressure pulse for model V1 was larger than the pulse for V2 and the elastic model in the exercise case. In this paper, we have successfully implemented and verified two viscoelastic wall models in a nonlinear 1D finite element blood flow solver and analyzed differences between these models in various idealized and physiological simulations, including exercise. The computational model of blood flow presented here can be utilized in further studies of the cardiovascular system incorporating viscoelastic wall properties.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.     

Numerical simulation of fluid–structure interaction in bypassed DeBakey III aortic dissection

It was found that bypass graft alone could achieve great effects in treating aortic dissection. In order to investigate the mechanical mechanism and the haemodynamic validity of the bypassing treatment for DeBakey III aortic dissection, patient-specific models of DeBakey III aortic dissection treated with different bypassing strategies were constructed. One of the bypassing strategies is bypassing between ascending aorta and abdominal aorta, and the other is bypassing between left subclavian artery and abdominal aorta. Numerical simulations under physiological flow conditions based on fluid–structure interaction were performed using finite element method. The results show that blood flow velocity, pressure and vessel wall displacement of false lumen are all reduced after bypassing. This phenomenon indicates that bypassing is an effective surgery for the treatment of DeBakey III aortic dissection. The effectiveness to cure through lumen is better when bypassing between left subclavian artery and abdominal aorta, while the effectiveness to cure blind lumen is better when bypassing between ascending aorta and abdominal aorta.     

Pulsatile non-Newtonian haemodynamics in a 3D bifurcating abdominal aortic aneurysm model

Numerical prediction of non-Newtonian blood flow in a 3D abdominal aortic aneurysm bifurcating model is carried out. The non-Newtonian Carreau model is used to characterise the shear thinning behaviour of the human blood. A physical inlet velocity waveform incorporating a radial velocity distribution reasonably representative of a practical case configuration is employed. Case studies subject to both equal and unequal outlet pressures at iliac bifurcations are presented to display convincingly the downstream pressure influences on the flow behaviour within the aneurysm. Simulations indicate that the non-Newtonian aspects of the blood cannot at all be neglected or given a cursory treatment. The wall shear stress (WSS) is found to change significantly at both the proximal and distal ends of the aneurysm. At the peak systole, the WSS is peak around the bifurcation point, whereas the WSS becomes zero in the bifurcation point. Differential downstream pressure fields display significant effects regarding the flow evolution in the iliac arteries, whereas little or no effects are observed directly on the flow details in the aneurysm.     

A computational method for calculating distensibility of the blood vessel in vivo.

A computational method for calculating the dynamic distensibility of the vessel wall in vivo, developed on the basis of the pressure pulse transmission, is proposed. Distensibilities of descending thoracic aorta, abdominal aorta, and femoral artery in normal dogs, and of femoral artery of a typical dog under the action of vasoactive drugs, have been calculated. In femoral artery it is compared with the values of the diameter change/pressure change. Comparison of the results clearly indicate the feasibility of the proposed method. The order of distensibility found is: descending thoracic aorta greater than abdominal aorta greater than femoral artery.     

大鼠心力衰竭模型的构建与鉴定

目的比较主动脉弓缩窄和腹主动脉缩窄复制心力衰竭衰模型的异同,探索快速有效的心衰动物模型。方法将大鼠分为主动脉缩窄手术组,腹主动脉缩窄手术组和对照组（C组）。主动脉缩窄手术组实施颈部手术,在主动脉弓处缩窄动脉直径;腹主动脉缩窄手术组实施腹部手术,在腹主动脉处缩窄动脉直径;C组实施颈部手术但不实施动脉缩窄手术。各组实验动物均正常喂养4～6周后进行心脏的超声检测和心脏血流动力学检测。结果心脏超声结果显示：主动脉弓缩窄手术组左心室壁厚度和左心室腔内径在术后4周明显高于正常组;而腹主动脉缩窄手术组左心室壁厚度和左心室腔内径在术后4周较正常组没有明显增加。术后6周,腹主动脉缩窄手术组左心室壁厚度和左心室腔内径都明显增加,而主动脉弓缩窄手术组左心室壁厚度没有明显改变,左心室腔内经明显增加。血流动力学指标显示：主动脉弓缩窄手术组LVESP、LVEDP、LVDP、±dp/dtmax都明显低于腹主动脉缩窄手术组。结论主动脉弓缩窄手术复制心肌肥大导致心功能衰竭模型效果明显快于腹主动脉缩窄手术复制的心肌肥大导致心功能衰竭模型。     

The impact of simplified boundary conditions and aortic arch inclusion on CFD simulations in the mouse aorta: a comparison with mouse-specific reference data

Computational fluid dynamics (CFD) simulations allow for calculation of a detailed flow field in the mouse aorta and can thus be used to investigate a potential link between local hemodynamics and disease development. To perform these simulations in a murine setting, one often needs to make assumptions (e.g. when mouse-specific boundary conditions are not available), but many of these assumptions have not been validated due to a lack of reference data. In this study, we present such a reference data set by combining high-frequency ultrasound and contrast-enhanced micro-CT to measure (in vivo) the time-dependent volumetric flow waveforms in the complete aorta (including seven major side branches) of 10 male ApoE -/- deficient mice on a C57Bl/6 background. In order to assess the influence of some assumptions that are commonly applied in literature, four different CFD simulations were set up for each animal: (i) imposing the measured volumetric flow waveforms, (ii) imposing the average flow fractions over all 10 animals, presented as a reference data set, (iii) imposing flow fractions calculated by Murray's law, and (iv) restricting the geometrical model to the abdominal aorta (imposing measured flows). We found that - even if there is sometimes significant variation in the flow fractions going to a particular branch - the influence of using average flow fractions on the CFD simulations is limited and often restricted to the side branches. On the other hand, Murray's law underestimates the fraction going to the brachiocephalic trunk and strongly overestimates the fraction going to the distal aorta, influencing the outcome of the CFD results significantly. Changing the exponential factor in Murray's law equation from 3 to 2 (as suggested by several authors in literature) yields results that correspond much better to those obtained imposing the average flow fractions. Restricting the geometrical model to the abdominal aorta did not influence the outcome of the CFD simulations. In conclusion, the presented reference dataset can be used to impose boundary conditions in the mouse aorta in future studies, keeping in mind that they represent a subsample of the total population, i.e., relatively old, non-diseased, male C57Bl/6 ApoE -/- mice.     

The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta

Purpose

The goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples.

Methods

The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens.

Results

The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r² = 0.3099; P = 0.0047).

Conclusion

Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

     

The effects of prostacyclin and thromboxane analogue (U46619) on the fetal circulation and umbilical flow velocity waveforms

In placental insufficiency and pre-eclampsia the relative production rates of prostacyclin and thromboxane by the placenta and umbilical vessels are altered and the Doppler umbilical flow velocity waveform shows a high resistance pattern. To investigate the control of umbilical placental blood flow by those eicosanoids either prostacyclin (10 micrograms/min), or the thromboxane analogue U46619 (10 ng/min) was infused into the distal aorta of 12 chronically catheterized fetal lambs at day 125. Thromboxane produced a rise in mean arterial pressure and a rise in the systolic diastolic ratio of the umbilical artery flow waveform (2.6 to 3.1; P less than 0.05). Umbilical blood flow did not change and there was no evidence of altered flow to other organs. Prostacyclin caused a fall in fetal mean arterial pressure and a decrease in the umbilical artery systolic diastolic ratio (2.9 to 2.4; P less than 0.05). Prostacyclin produced a three-fold increase in lung perfusion (and the onset of fetal breathing movements) and this was associated with a 90% reduction in muscle blood flow (hindlimb muscle flow reduced from 12.5 to 1.1 ml.min-1 100g-1; P less than 0.01). We conclude that the local release of thromboxane in the fetal placental vascular bed could account for the rise in systolic diastolic ratio seen in umbilical placental insufficiency.     

Cardiovascular response to lower body negative pressure before and after 20 days horizontal bed rest

To evaluate the effects of 20 days bed rest (BR) on cardiovascular system in normal subjects, left ventricular (LV) echocardiography and vascular ultrasound of the common carotid artery and abdominal aorta were performed during rest and a supine lower body negative pressure (LBNP) test in 14 healthy volunteers (mean age: 22 years) before and after BR. After BR, heart rates (HR) at rest and during LBNP (-40 mmHg) increased. In contrast, LV dimensions, stroke volume, and blood pressures decreased both at rest and during LBNP. Also LBNP tolerance time decreased after BR. Although resting cardiac output (CO) and abdominal aortic flow decreased after bed rest, CO and abdominal aortic flow were unchanged during LBNP comparing before and after BR. Common carotid artery flows both at rest and during LBNP showed no change after BR. LBNP did not increase HR before BR, but increased HR prominently after BR. In conclusion, LBNP tolerance time and LV size during LBNP decreased after BR, suggesting orthostatic intolerance due to a decreased blood volume. However, CO and flow in the abdominal aorta and common carotid artery during LBNP were similar before and after BR due to a compensatory increase after BR.     

Towards in vivo aorta material identification and stress estimation

This paper addresses the problem of constructing a mechanical model for the abdominal aorta and calibrating its parameters to in vivo measurable data. The aorta is modeled as a pseudoelastic, thick-walled, orthotropic, residually stressed cylindrical tube, subjected to an internal pressure. The model parameters are determined by stating a minimization problem for the model pressure and computing the optimal solution by a minimization algorithm. The data used in this study is in vivo pressure–diameter data for the abdominal aorta of a 24-year-old man. The results show that the axial, circumferential and radial stresses have magnitudes in the span 0 to 180 kPa. Furthermore, the results show that it is possible to determine model parameters directly from in vivo measurable data. In particular, the parameters describing the residual stress distribution can be obtained without interventional procedures.     

Wave intensity in the ascending aorta: effects of arterial occlusion

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.