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.     

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

The non-Newtonian fluid flow in a bifurcation model with a non-planar daughter branch is investigated by using finite element method to solve the three-dimensional Navier–Stokes equations coupled with a non-Newtonian constitutive model, in which the shear thinning behavior of the blood fluid is incorporated by the Carreau–Yasuda model. The objective of this study is to investigate the influence of the non-Newtonian property of fluid as well as of curvature and out-of-plane geometry in the non-planar daughter vessel on wall shear stress (WSS) and flow phenomena. In the non-planar daughter vessel, the flows are typified by the skewing of the velocity profile towards the outer wall, creating a relatively low WSS at the inner wall. In the downstream of the bifurcation, the velocity profiles are shifted towards the flow divider. The low WSS is found at the inner walls of the curvature and the lateral walls of the bifurcation. Secondary flow patterns that swirl fluid from the inner wall of curvature to the outer wall in the middle of the vessel are also well documented for the curved and bifurcating vessels. The numerical results for the non-Newtonian fluid and the Newtonian fluid with original Reynolds number and the corresponding rescaled Reynolds number are presented. Significant difference between the non-Newtonian flow and the Newtonian flow is revealed; however, reasonable agreement between the non-Newtonian flow and the rescaled Newtonian flow is found. Results of this study 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.     

Computational study of pulsatile blood flow in prototype vessel geometries of coronary segments

The spatial and temporal distributions of wall shear stress (WSS) in prototype vessel geometries of coronary segments are investigated via numerical simulation, and the potential association with vascular disease and specifically atherosclerosis and plaque rupture is discussed. In particular, simulation results of WSS spatio-temporal distributions are presented for pulsatile, non-Newtonian blood flow conditions for: (a) curved pipes with different curvatures, and (b) bifurcating pipes with different branching angles and flow division. The effects of non-Newtonian flow on WSS (compared to Newtonian flow) are found to be small at Reynolds numbers representative of blood flow in coronary arteries. Specific preferential sites of average low WSS (and likely atherogenesis) were found at the outer regions of the bifurcating branches just after the bifurcation, and at the outer-entry and inner-exit flow regions of the curved vessel segment. The drop in WSS was more dramatic at the bifurcating vessel sites (less than 5% of the pre-bifurcation value). These sites were also near rapid gradients of WSS changes in space and time – a fact that increases the risk of rupture of plaque likely to develop at these sites. The time variation of the WSS spatial distributions was very rapid around the start and end of the systolic phase of the cardiac cycle, when strong fluctuations of intravascular pressure were also observed. These rapid and strong changes of WSS and pressure coincide temporally with the greatest flexion and mechanical stresses induced in the vessel wall by myocardial motion (ventricular contraction). The combination of these factors may increase the risk of plaque rupture and thrombus formation at these sites.     

Modeling the effect of blood vessel bifurcation ratio on occlusive thrombus formation

Vascular geometry is a major determinant of the hemodynamics that promote or prevent unnecessary vessel occlusion from thrombus formation. Bifurcations in the vascular geometry are repeating structures that introduce flow separation between parent and daughter vessels. We modelled the blood flow and shear rate in a bifurcation during thrombus formation and show that blood vessel bifurcation ratios determine the maximum shear rate on the surface of a growing thrombus. We built an analytical model that may aid in predicting microvascular bifurcation ratios that are prone to occlusive thrombus formation. We also observed that bifurcation ratios that adhere to Murray’s law of bifurcations may be protected from occlusive thrombus formation. These results may be useful in the rational design of diagnostic microfluidic devices and microfluidic blood oxygenators.     

Spatial and temporal role of the apelin/APJ system in the caliber size regulation of blood vessels during angiogenesis

Blood vessels change their caliber to adapt to the demands of tissues or organs for oxygen and nutrients. This event is mainly organized at the capillary level and requires a size-sensing mechanism. However, the molecular regulatory mechanism involved in caliber size modification in blood vessels is not clear. Here we show that apelin, a protein secreted from endothelial cells under the activation of Tie2 receptor tyrosine kinase on endothelial cells, plays a role in the regulation of caliber size of blood vessel through its cognate receptor APJ, which is expressed on endothelial cells. During early embryogenesis, APJ is expressed on endothelial cells of the new blood vessels sprouted from the dorsal aorta, but not on pre-existing endothelial cells of the dorsal aorta. Apelin-deficient mice showed narrow blood vessels in intersomitic vessels during embryogenesis. Apelin enhanced endothelial cell proliferation in the presence of vascular endothelial growth factor and promoted cell-to-cell aggregation. These results indicated that the apelin/APJ system is involved in the regulation of blood vessel diameter during angiogenesis.     

The influence of the non-Newtonian properties of blood on the flow in large arteries: steady flow in a carotid bifurcation model.

Laser Doppler anemometry experiments and finite element simulations of steady flow in a three dimensional model of the carotid bifurcation were performed to investigate the influence of non-Newtonian properties of blood on the velocity distribution. The axial velocity distribution was measured for two fluids: a non-Newtonian blood analog fluid and a Newtonian reference fluid. Striking differences between the measured flow fields were found. The axial velocity field of the non-Newtonian fluid was flattened, had lower velocity gradients at the divider wall, and higher velocity gradients at the non-divider wall. The flow separation, as found with the Newtonian fluid, was absent. In the computations, the shear thinning behavior of the analog blood fluid was incorporated through the Carreau-Yasuda model. The viscoelastic properties of the fluid were not included. A comparison between the experimental and numerical results showed good agreement, both for the Newtonian and the non-Newtonian fluid. Since only shear thinning was included, this seems to be the dominant non-Newtonian property of the blood analog fluid under steady flow conditions.     

Assessment of energy requirement for the retinal arterial network in normal and hypertensive subjects

The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement.     

A new approach to blood flow simulation in vascular networks

A proper analysis of blood flow is contingent upon accurate modelling of the branching pattern and vascular geometry of the network of interest. It is challenging to reconstruct the entire vascular network of any organ experimentally, in particular the pulmonary vasculature, because of its very high number of vessels, complexity of the branching pattern and poor accessibility in vivo. The objective of our research is to develop an innovative approach for the reconstruction of the full pulmonary vascular tree from available morphometric data. Our method consists of the use of morphometric data on those parts of the pulmonary vascular tree that are too small to reconstruct by medical imaging methods. This method is a three-step technique that reconstructs the entire pulmonary arterial tree down to the capillary bed. Vessels greater than 2 mm are reconstructed from direct volume and surface analysis using contrast-enhanced computed tomography. Vessels smaller than 2 mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray's laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray's laws to every vessel bifurcation simultaneously leads to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the ?rst capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-de?ned Strahler system, are assigned. In conclusion, the present model provides a morphological foundation for future analysis of blood flow in the pulmonary circulation     

Interaction between alk1 and blood flow in the development of arteriovenous malformations

Arteriovenous malformations (AVMs) are fragile direct connections between arteries and veins that arise during times of active angiogenesis. To understand the etiology of AVMs and the role of blood flow in their development, we analyzed AVM development in zebrafish embryos harboring a mutation in activin receptor-like kinase I (alk1), which encodes a TGFβ family type I receptor implicated in the human vascular disorder hereditary hemorrhagic telangiectasia type 2 (HHT2). Our analyses demonstrate that increases in arterial caliber, which stem in part from increased cell number and in part from decreased cell density, precede AVM development, and that AVMs represent enlargement and stabilization of normally transient arteriovenous connections. Whereas initial increases in endothelial cell number are independent of blood flow, later increases, as well as AVMs, are dependent on flow. Furthermore, we demonstrate that alk1 expression requires blood flow, and despite normal levels of shear stress, some flow-responsive genes are dysregulated in alk1 mutant arterial endothelial cells. Taken together, our results suggest that Alk1 plays a role in transducing hemodynamic forces into a biochemical signal required to limit nascent vessel caliber, and support a novel two-step model for HHT-associated AVM development in which pathological arterial enlargement and consequent altered blood flow precipitate a flow-dependent adaptive response involving retention of normally transient arteriovenous connections, thereby generating AVMs.     

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.     

Pulsatile non-newtonian blood flow in three-dimensional carotid bifurcation models: a numerical study of flow phenomena under different bifurcation angles

Flow and stress patterns in human carotid artery bifurcation models, which differ in the bifurcation angle, are analysed numerically under physiologically relevant flow conditions. The governing Navier-Stokes equations describing pulsatile, three-dimensional flow of an incompressible non-Newtonian fluid are approximated using a pressure correction finite element method, which has been developed recently. The non-Newtonian behaviour of blood is modelled using Casson's relation, based on measured dynamic viscosity. The study concentrates on flow and stress characteristics in the carotid sinus. The results show that the complex flow in the sinus is affected by the angle variation. The magnitude of reversed flow, the extension of the recirculation zone in the outer sinus region and the duration of flow separation during the pulse cycle as well as the resulting wall shear stress are clearly different in the small angle and in the large angle bifurcation. The haemodynamic phenomena, which are important in atherogenesis, are more pronounced in the large angle bifurcation.     

Modelling and simulation of the behaviour of a biofluid in a microchannel biochip separator

This paper reports an investigation into the flow behaviour of a biofluid in a microchannel systems through conceptual analysis and modelling. The application is the design of a microfluidic chip developed for the separation of plasma from blood. The effect of key design features of the microchannels on the flow behaviour of the biofluid is explored. These include geometric features such as the constriction, bending channel, bifurcation and the channel length ratio between the main and side channels. The performance of each design is discussed in terms of separation efficiency of the red blood cells with respect to the rest of the medium. Particular phenomena such as the Fahraeus and Fahraeus–Lindqvist effects, the Zweifach–Fung bifurcation law and the cell-free layer are discussed. In this paper, the fluid is modelled as a single-phase flow assuming either Newtonian or Non-Newtonian behaviour to investigate the effect of the fluid viscosity on both flow and separation efficiency. For a flow rate-controlled Newtonian flow system, it is found that viscosity and outlet pressure have little effect on the velocity distribution through each of the microchannels. For a diluted fluid where the flow in the whole channel system is modelled with a uniform viscosity, less plasma is separated from blood than observed in the non-Newtonian case. This results in an increase in the flow rate ratio between the main and side channels. A comparison of Newtonian and non-Newtonian flows shows that both flows tend to behave identically with an increase in the shear strain rate.     

Modelling and simulation of the behaviour of a biofluid in a microchannel biochip separator

This paper reports an investigation into the flow behaviour of a biofluid in a microchannel systems through conceptual analysis and modelling. The application is the design of a microfluidic chip developed for the separation of plasma from blood. The effect of key design features of the microchannels on the flow behaviour of the biofluid is explored. These include geometric features such as the constriction, bending channel, bifurcation and the channel length ratio between the main and side channels. The performance of each design is discussed in terms of separation efficiency of the red blood cells with respect to the rest of the medium. Particular phenomena such as the Fahraeus and Fahraeus-Lindqvist effects, the Zweifach-Fung bifurcation law and the cell-free layer are discussed. In this paper, the fluid is modelled as a single-phase flow assuming either Newtonian or Non-Newtonian behaviour to investigate the effect of the fluid viscosity on both flow and separation efficiency. For a flow rate-controlled Newtonian flow system, it is found that viscosity and outlet pressure have little effect on the velocity distribution through each of the microchannels. For a diluted fluid where the flow in the whole channel system is modelled with a uniform viscosity, less plasma is separated from blood than observed in the non-Newtonian case. This results in an increase in the flow rate ratio between the main and side channels. A comparison of Newtonian and non-Newtonian flows shows that both flows tend to behave identically with an increase in the shear strain rate.     

Low Reynolds number equi-bifurcation flow in a two-dimensional channel

The fluid flow in some physiological vessels such as the blood flow in blood vessels and the air flow through bronchi and bronchioles in the lungs undergoes a large number of bifurcations. The understanding of the bifurcation flow is of importance for a better comprehension of its effect in the blood and the air circulatory systems of the living body. The Reynolds number of flow in large blood vessels and bronchi is high and fluid inertia plays a dominant role in the bifurcation flow in such vessels. In small caliber blood vessels such as arterioles and capillaries, and bronchioles, the Reynolds number of flow is quite low and the effect of fluid inertia is negligible compared to the pressure and shear forces. In order to have a quantitative understanding of the bifurcation flow at low Reynolds numbers, the low Reynolds number equi-bifurcation flow in a two-dimensional channel at zero bifurcation angle is studied based on the Stokes approximation. The solution of the problem is posed as an infinite series, where the truncated version is used in numerical calculations. The results of this analysis is discussed in connection with the bifurcation flow of blood in small caliber blood vessels and that of the air in bronchioles in the lung.     

Bifurcation asymmetry of the porcine coronary vasculature and its implications on coronary flow heterogeneity

The branching pattern of the coronary arteries and veins is asymmetric, i.e., many small vessels branch off of a large trunk such that the two daughter vessels at a bifurcation are of unequal diameters and lengths. One important implication of the geometric vascular asymmetry is the dispersion of blood flow at a bifurcation, which leads to large spatial heterogeneity of myocardial blood flow. To document the asymmetric branching pattern of the coronary vessels, we computed an asymmetry ratio for the diameters and lengths of all vessels, defined as the ratio of the daughter diameters and lengths, respectively. Previous data from silicone elastomer cast of the entire coronary vasculature including arteries, arterioles, venules, and veins were analyzed. Data on smaller vessels were obtained from histological specimens by optical sectioning, whereas data on larger vessels were obtained from vascular casts. Asymmetry ratios for vascular areas, volumes, resistances, and flows of the various daughter vessels were computed from the asymmetry ratios of diameters and lengths for every order of mother vessel. The results show that the largest orders of arterial and venous vessels are most asymmetric and the degree of asymmetry decreases toward the smaller vessels. Furthermore, the diameter asymmetry at a bifurcation is significantly larger for the coronary veins (1.7-6.8 for sinus veins) than the corresponding arteries (1.5-5.8 for left anterior descending coronary artery) for orders 2-10, respectively. The reported diameter asymmetry at a bifurcation leads to significant heterogeneity of blood flow at a bifurcation. Hence, the present data quantify the dispersion of blood flow at a bifurcation and are essential for understanding flow heterogeneity in the coronary circulation.     

Red blood cells augment leukocyte rolling in a virtual blood vessel

Leukocyte rolling and arrest on the vascular endothelium is a central event in normal and pathological immune responses. However, rigorous estimation of the fluid and surface forces involved in leukocyte-endothelial interactions has been difficult due to the particulate, non-Newtonian nature of blood. Here we present a Lattice-Boltzmann approach to quantify forces exerted on rolling leukocytes by red blood cells in a "virtual blood vessel." We report that the normal force imparted by erythrocytes is sufficient to increase leukocyte binding and that increases in tangential force and torque can promote rolling of previously adherent leukocytes. By simulating changes in hematocrit we show that a close "envelopment" of the leukocyte by the red blood cells is necessary to produce significant changes in the forces. This novel approach can be applied to a large number of biological and industrial problems involving the complex flow of particulate suspensions.     

Optimality principle in vascular bifurcation

The optimal geometry of the vascular bifurcation is interpreted on the basis of the principle of minimum work. We consider the energy expenditure due to the viscosity of blood, and that for maintaining the metabolic states of the blood cells and of the vessel wall. It is shown that the optimal radii of the stem and branch vessels and the optimal branching angle are related to two parameters which represent the morphologic and metabolic states of the blood and the vessel wall. In the special case of symmetrical bifurcation, it was found that as the metabolic demand of the vessel wall becomes more apparent when compared with that of the blood, the branch radius relative to that of the stem takes values of from 0.794 down to 0.758 minimally, and the angle from 37.5 degrees up to 48.7 degrees maximally with respect to the direction of the stem.     

Analysis of non-Newtonian effects within an aorta-iliac bifurcation region

The geometry of the arteries at or near arterial bifurcation influences the blood flow field, which is an important factor affecting arteriogenesis. The blood can act sometimes as a non-Newtonian fluid. However, many studies have argued that for large and medium arteries, the blood flow can be considered to be Newtonian. In this work a comprehensive investigation of non-Newtonian effects on the blood fluid dynamic behavior in an aorta-iliac bifurcation is presented. The aorta-iliac geometry is reconstructed with references to the values reported in Shah et al. (1978); the 3D geometrical model consists of three filleted cylinders of different diameters. Governing equations with the appropriate boundary conditions are solved with a finite-element code. Different rheological models are used for the blood flow through the lumen and detailed comparisons are presented for the aorta-iliac bifurcation. Results are presented in terms of the velocity profiles in the bifurcation zone and Wall Shear Stress (WSS) for different sides of the bifurcation both for male and female geometries, showing that the Newtonian fluid assumption can be made without any particular loss in terms of accuracy with respect to the other more complex rheological models.     

A study on the non-linear flow of blood through arteries

The pulsatile flow of blood through arteries is investigated in this paper by treating the blood vessel as a thin-walled anisotropic, non-linearly viscoelastic, incompressible circular cylindrical shell; nonlinearities of the flow of blood are also paid due consideration. The displacement components of the vessel wall are obtained from the equations of equilibrium which have been linearized by employing the principle of superimposition of a small deformation on a state of known finite deformation. The influence of the wall deformation on the flow properties of blood, has been accounted for by considering suitably formulated continuity conditions. A finitedifference scheme is employed for solving the flow equations together with the boundary and initial conditions by using the locally measured values of pressure and pressure gradient. Numerical results obtained for the velocity profile of blood flowing in a canine middle descending thoracic aorta have been presented through figures.