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.     

Effects of fluid viscoelasticity on the performance of an axial blood pump model

An aqueous Xanthan gum solution (XGS) was used as blood analog fluid to explore the influence of fluid viscoelasticity on the performance of an axial blood pump model. For comparison, a 39 wt% Newtonian aqueous glycerin solution (GS), the common fluid in blood pump tests, was also used as a working fluid. The experimental results showed that a higher head curve was obtained using XGS in the pump than using GS. The heads of the XGS that were computed using the viscoelastic turbulence model agreed well with the measured data. In contrast, the standard k-ε turbulence model failed to provide satisfactory predictions for the XGS. The computational results revealed that in most parts of the pump model flow fields, the Reynolds shear stress values and turbulent dissipation rates of the XGS were all lower than those of the GS. The hemolysis index of the pump model using the XGS was calculated to be only one-third of that using the GS.     

Rheological characteristics of semi-dilute chitosan solutions

The present work is concerned with experimental results on rheological characteristic properties of semi-dilute chitosan solutions in weakly acetic acid. The flow measurements were conducted on solutions of chitosan of various deacetylation degrees DD (62.8%–86.7%) with changing experimental conditions such as concentration (up to 5 g/100 mL), temperature (20°C–41°C) and shear rate applied (up to 10³s^?1). Chitosan solutions behave generally as a typical non-Newtonian shear-thinning fluid with a characteristic n-parameter lower than 1. The rheological n-parameter decreases with decreasing deacetylation degree and increasing solution concentration but it increases with increasing temperature. Because of strong intermolecular hydrogen bonding even at low concentration the chitosan macromolecules have a tendency to entangle and to network formation. The density of the molecular entanglements in the chitosan solution depends on concentration, temperature and shear rate applied. An effect of the deacetylation degree on the Huggins viscosity constant related to polymer solvent interaction is found. The most important results refer to the activation energy of viscous flow found from Arrhenius plots. The dependence of the activation energy on solution concentration, shear rate and DD is discussed.     

Experimental investigation of the flow of a blood analogue fluid in a replica of a bifurcated small artery

The scope of this work is to study the pulsatile flow of a blood mimicking fluid in a micro channel that simulates a bifurcated small artery, in which the Fahraeus-Lindqvist effect is insignificant. An aqueous glycerol solution with small amounts of xanthan gum was used for simulating viscoelastic properties of blood and in vivo flow conditions were reproduced. Local flow velocities were measured using micro Particle Image Velocimetry (μ-PIV). From the measured velocity distributions, the wall shear stress (WSS) and its variation during a pulse were estimated. The Reynolds numbers employed are relatively low, i.e. similar to those prevailing during blood flow in small arteries. Experiments both with a Newtonian and a non-Newtonian fluid (having asymptotic viscosity equal to the viscosity of the Newtonian one) proved that the common assumption that blood behaves as a Newtonian fluid is not valid for blood flow in small arteries. It was also shown that the outer wall of the bifurcation, which is exposed to a lower WSS, is more predisposed to atherosclerotic plaque formation. Moreover, this region in small vessels is shorter than the one in large arteries, as the developed secondary flow decays faster. Finally, the WSS values in small arteries were found to be lower than those in large ones.     

Rheological Study of Synovial Fluid Obtained from Dogs: Healthy,Pathological, and Post-Surgery,after Spontaneous Rupture of Cranial Cruciate Ligament

In the present study synovial fluid (SF) obtained from the stifle joint of healthy adult dogs and of dogs after cranial cruciate ligament rupture was analyzed regarding its rheological characteristics according to the condition of the joint. The viscoelastic and shear flow properties were measured at 25 and 38 °C. The results showed that the healthy SF exhibits practically temperature independent viscosity curve and satisfactory viscoelastic characteristics, i.e. G′ > G′′, over frequencies of 0.05–5 Hz, and characteristic relaxation time λ of the order of magnitude of 100 s. Creep measurements demonstrate that the zero shear viscosity was in the range of 10–100 Pa s. In shear flow viscosity measurements, by increasing [(g)\dot] \dot{\gamma } from 10⁻⁴ s⁻¹ up to 10³ s⁻¹, non-Newtonian shear thinning behavior was observed and the viscosity values were decreased from 10³ to 0.1 Pa s. On the contrary, in pathological conditions of cranial cruciate ligament rupture (CCLR), the measured viscosity was found drastically reduced, i.e. between 100 and 10 mPa s. The CCLR synovial fluid, similar to healthy SF, exhibits insignificant temperature dependence. The present study showed also that about one week after a surgery for CCLR repair the SF exhibits non-Newtonian behavior of dilute polymers. After two weeks from the operation, however, the rheological behavior converges to the one of healthy SF.     

Comparison of three rheological models of shear flow behavior studied on blood samples from post-infarction patients

Quantitative analysis of blood viscosity was performed on the basis of mathematical models of non-Newtonian fluid shear flow behavior (Casson, Ree-Eyring and Quemada). A total of 100 blood samples were drawn from clinically stable survivors of myocardial infarction, treated with aspirin or acenocoumarol and controls to these drugs. Whole blood and plasma viscosity were measured at a broad range of shear rates using a rotary-oscillating viscometer Contraves LS40. Numerical analysis of the experimental data was carried out by means of linear (for Casson) and non-linear regression for the remaining models. In the evaluation of the results, both the fit quality and physical interpretation of the models’ parameters were considered. The Quemada model fitted most precisely with the experimental findings and, despite the controversies concerning the relationship between in vivo tissue perfusion and in vitro rheological measurements, seemed to be a valuable method enhancing investigation possibilities of cardiovascular patients. Our results suggest that aspirin does not affect blood rheological properties, while acenocoumarol may slightly alter red cell deformability and rouleaux formation.     

Viscosity of animal erythrocyte suspensions mixed with a perflurocarbon emulsion

Artificial blood substitutes (ABS) offer an alternative to donated blood. Increasing the oxygen carrying capacity of blood plasma through the addition of a Perfluorocarbon emulsion (PFE) is one approach in creating a blood substitute. The peripheral resistance of the circulatory system may be altered depending on the rheological properties of the ABS. Measurements of the rheological behavior of mixtures of a PFE, Oxygent, and erythrocyte suspensions were conducted at room temperature at different hematocrits using sheep (nonaggregating) and swine (aggregating) erythrocytes. The pure PFE was found to be shear thinning. Adding 6 and 12 g per 100 mL of sheep blood at the various hematocrits increased the viscosity of the suspension from as low as 4% (6 g PFE/40% Hct) to as high as 26.5% (12 g PFE/plasma). The nonaggregating sheep erythrocyte and PFE mixtures exhibited Newtonian behavior. Shear thinning behavior continued upon addition of 6 and 12 g per 100 mL of swine blood at the various hematocrits, with a slight increase in viscosity in most cases. It was observed that adding 12 g of PFE (approximately 3 x intended clinical dose) to 40% Hct swine blood at room temperature led to a significant decrease in viscosity.     

Experimental flow studies in an elastic Y-model.

To determine the causes and history of atherosclerosis it is necessary to understand the hemodynamic parameters of blood circulation. Hemodynamic parameters play an important role in the formation of atherosclerotic plaques, especially near bends and bifurcations where the flow separates from the wall. Here the flow is laminar and non-axial with eddies, secondary flow, flow separation and stagnation points. Stenoses are found predominantly in flow separation areas. Therefore, it is important to separately study the following flow parameters: steady and pulsatile flow, wall elasticity and non-Newtonian flow behavior of blood. A simplified silicon elastic y-model simulating the human carotid artery was used for the analysis of these parameters. This model can be used for numerical studies as well. Flow was visualized at steady flow using dyes and at pulsatile flow with a photoelastic apparatus and a birefringent solution. The local axial velocity at steady and pulsatile flow was determined with a one-component Laser-Doppler-Anemometer (LDA). Pulsatile flow was generated by a piston membrane pump. A glycerin-water solution was used to simulate the Newtonian flow behavior of blood. A DMSO-Separan water solution was used to simulate the non-Newtonian flow behavior. Pulsatile flow creates higher and lower shear rates so called oscillating shear rate compare to steady flow depending on the velocity amplitude. The non-Newtonian fluid showed a markedly different flow behavior than the Newtonian fluid especially in areas of flow separation. Shear gradients were calculated from these velocity measurements using a bicubic spline interpolation. Shear stresses were calculated from these velocity shear gradients and the viscosity of the non-Newtonian fluid at these shear gradients. At special areas, high shear stresses > 10 Pa were found. The elasticity of the model wall also influences the flow behavior. The measurements showed that the characteristics of pulsatile flow and the elasticity of the model wall should be observed concomitantly. This paper presents the steady and pulsatile flow with a Newtonian and non-Newtonian fluid in an elastic model.     

Flow of micropolar fluid through a tube with stenosis

A mathematical model for the steady flow of non-Newtonian fluid through a stenotic region is presented. The results indicate that the general shape and size of the stenosis together with rheological properties of blood are important in understanding the flow characteristics and the presence of flow separation.     

Formation of supermolecular structures of polysaccharide-surfactant complexes in aqueous solutions. Influence of the polymer backbone

Novel water-soluble derivatives of cellulose, amylose and dextran are synthesized and investigated with regard to their special interactions with the anionic surfactant sodium dodecylsulfate (SDS) by means of rheological flow- and oscillatory measurements as well as electrolytic conductivity in aqueous solution. The derivatives of amylose and dextran show a continuous adsorption of SDS with increasing surfactant concentration leading to an increase of the viscosity and of the viscous part of the shear modulus of the solution. Only low elastic parts are detectable. In contrast, the behaviour of cellulose derivatives differs extremely with increasing amount of SDS. The viscosity and the elastic part of the shear modulus of aqueous solutions reach a well pronounced maximum and then drop almost to the initial values. A similar behaviour is also observed by adding the cationic surfactant hexadecyltrimethylammonium bromide. It is concluded that the observed differences in properties of the cellulose derivatives on the one side and derivatives of amylose and dextran on the other are cause by the structure of the polymer main chain, because the side groups for all of these polymers are comparable.     

Amphiphilic derivatives of sodium alginate and hyaluronate for cartilage repair: rheological properties

Various amphiphilic derivatives of sodium alginate and hyaluronate were prepared by covalent fixation of long alkyl chains (dodecyl and octadecyl) with various ratios on the polysaccharide backbones via ester functions. In the semidilute regime, aqueous solutions of the resulting compounds exhibited the typical rheological properties of hydrophobically associating polymers: tremendous enhancement of zero shear rate Newtonian viscosity, steep shear-thinning behavior, and formation of physically cross-linked gel-like networks. The influence of the alkyl chain length, its content on the polysaccharide and of the polymer concentration in the solution was well identified. All obtained results are discussed with respect to the schedule of conditions related to materials, which could be used for cartilage repair, such as in synovial fluid viscosupplementation as well as in cartilage replacement. In particular, it is seen that HA-C(12)-5 (hyaluronate substituted with 5% of dodecyl chains) and HA-C(18)-1 (hyaluronate substituted with 1% of octadecyl chains) in a 0.15N NaCl solution at 8 g/L have rheological properties quite similar to those of healthy synovial fluid. On the other hand, the rheological parameters of solutions at 8 g/L in 0.15N NaCl of some of derivatives, such as, for example, AA-C(12)-8 (alginate substituted with 8% of dodecyl chains) or HA-C(18)-2, are well fitted for a use in cartilage repair.     

Behavior of In Situ Cross‐Linked Hydrogels with Rapid Gelation Kinetics on Contact with Physiological Fluids

The impact of different physiological fluids on the rheological properties of gellan gum is investigated using a commercially available rheometer with a modified lower plate. The power of this method is demonstrated by measuring in real time, the rapid gelation kinetics, and gel strength of gellan gum exposed to simulated gastric fluid, lacrimal fluid, saliva, and wound fluid (all having a different ionic composition), highlighting potential use in the intelligent design of in situ gelling delivery systems. Changes in rheological behavior are examined in situ, gelation kinetics are modeled, and microstructure analyzed in the different simulated physiological environments.     

Fontan术血流动力学非牛顿特性研究

目的 分析计算模拟中血液非牛顿特性对Fontan术后血流动力学的影响。方法 基于Fontan术后患者个体化三维血管模型,临床超声实测数据作为边界条件,分别选取常用的牛顿流体模型、非牛顿流体模型中的Casson模型与Carreau模型进行血流动力学模拟,计算血流分配比、能量损失、壁面切应力、非牛顿重要性系数等血流动力学参数,比较不同流体模型之间血流动力学参数差异。结果 流体模型对血流分配比影响小,非牛顿流体模型的能量损失较牛顿流体模型高,其中Casson模型最高。在下腔静脉中有明显回流、血流扰乱区域,并伴有低壁面切应力分布。在低流速时,牛顿流体模型下腔静脉血流扰乱更明显。非牛顿重要性系数显示在下腔静脉的非牛顿特性显著。结论 非牛顿特性在下腔静脉的低速回流区域影响显著,模拟患者个体化的Fontan血流动力学时应考虑血液的非牛顿特性。     

Cylinders vs. Spheres: Biofluid Shear Thinning in Driven Nanoparticle Transport

Increasingly, the research community applies magnetophoresis to micro and nanoscale particles for drug delivery applications and the nanoscale rheological characterization of complex biological materials. Of particular interest is the design and transport of these magnetic particles through entangled polymeric fluids commonly found in biological systems. We report the magnetophoretic transport of spherical and rod-shaped particles through viscoelastic, entangled solutions using lambda-phage DNA (λ-DNA) as a model system. In order to understand and predict the observed phenomena, we fully characterize three fundamental components: the magnetic field and field gradient, the shape and magnetic properties of the probe particles, and the macroscopic rheology of the solution. Particle velocities obtained in Newtonian solutions correspond to macroscale rheology, with forces calculated via Stokes Law. In λ-DNA solutions, nanorod velocities are 100 times larger than predicted by measured zero-shear viscosity. These results are consistent with particles experiencing transport through a shear thinning fluid, indicating magnetically driven transport in shear thinning may be especially effective and favor narrow diameter, high aspect ratio particles. A complete framework for designing single-particle magnetic-based delivery systems results when we combine a quantified magnetic system with qualified particles embedded in a characterized viscoelastic medium.     

Changes in the mechanical and adhesive behaviour of human neutrophils on cooling in vitro

Changes in the rheological properties of neutrophils may influence flow in microvessels that are cooled below normal body temperature. We investigated the effects of temperature on the mechanical and adhesive properties of human neutrophils by measuring transit times for individual cells flowing through 8-microm-pores in filters, and adhesion to P-selectin for cells perfused over a monolayer of activated platelets. Pore transit time increased as temperature was decreased from 37 degrees C to 0 degrees C. Upon rapid cooling, there was an instantaneous increase attributable to changes in aqueous viscosity. Interestingly, at 10 degrees C specifically, there was an additional increase in transit time, which was abolished by the inhibitor of actin polymerization, cytochalasin B. This meant that by 15 min, transit time at 10 degrees C was greater than at 0 degrees C. Most adherent cells on P-selectin were rolling, rather than stationary, at 10, 26 or 37 degrees C. The velocity of rolling slowed with decreasing temperature. The total number of adherent cells decreased with increasing wall shear rate, but for a given shear rate there was relatively little effect of temperature on attachment. However, when adhesion at 10, 26 or 37 degrees C was compared at equal shear stress (taking into account fluid viscosity), adhesion was greatest at 10 degrees C. Measurements of immunofluorescence showed that exposure to 10 degrees C gradually increased expression of beta2-integrin CD11b/CD18, but this did not cause transformation to stationary adhesion with time in the flow assay. Thus, neutrophils show an anomalous rheological response around 10 degrees C, which may impair local microcirculation in the cold. On rewarming, "activated" cells might inhibit recovery or become released into the systemic circulation.     

Compliant model of a coupled sequential coronary arterial bypass graft: effects of vessel wall elasticity and non-Newtonian rheology on blood flow regime and hemodynamic parameters distribution

We have recently developed a novel design for coronary arterial bypass surgical grafting, consisting of coupled sequential side-to-side and end-to-side anastomoses. This design has been shown to have beneficial blood flow patterns and wall shear stress distributions which may improve the patency of the CABG, as compared to the conventional end-to-side anastomosis. In our preliminary computational simulation of blood flow of this coupled sequential anastomoses design, the graft and the artery were adopted to be rigid vessels and the blood was assumed to be a Newtonian fluid. Therefore, the present study has been carried out in order to (i) investigate the effects of wall compliance and non-Newtonian rheology on the local flow field and hemodynamic parameters distribution, and (ii) verify the advantages of the CABG coupled sequential anastomoses design over the conventional end-to-side configuration in a more realistic bio-mechanical condition. For this purpose, a two-way fluid-structure interaction analysis has been carried out. A finite volume method is applied to solve the three-dimensional, time-dependent, laminar flow of the incompressible, non-Newtonian fluid; the vessel wall is modeled as a linearly elastic, geometrically non-linear shell structure. In an iteratively coupled approach the transient shell equations and the governing fluid equations are solved numerically. The simulation results indicate a diameter variation ratio of up to 4% and 5% in the graft and the coronary artery, respectively. The velocity patterns and qualitative distribution of wall shear stress parameters in the distensible model do not change significantly compared to the rigid-wall model, despite quite large side-wall deformations in the anastomotic regions. However, less flow separation and reversed flow is observed in the distensible models. The wall compliance reduces the time-averaged wall shear stress up to 32% (on the heel of the conventional end-to-side model) and somewhat increases the oscillatory nature of the flow. It is found that the effects of wall compliance and non-Newtonian rheology are not independent, and they interact with each other. In spite of the modest influence of wall compliance and non-Newtonian rheology on the hemodynamic parameters distribution, the inclusion of these properties has unveiled further advantages of the coupled sequential anastomoses model over the conventional end-to-side anastomosis which had not been revealed in the previous study with the rigid-wall and Newtonian fluid models. Hence, the inclusion of wall compliance and non-Newtonian rheology in flow simulation of blood vessels can be essential in quantitative and comparative investigations.     

Time dependent non-Newtonian numerical study of the flow field in a realistic model of aortic arch

A three-dimensional time dependent numerical simulation was performed in a geometric model of aortic arch complete with a realistic aortic root and major branches originating from the arch, for a peak Reynolds number set at 2200 and Womersley number set at 20.4. The computational fluid dynamic analysis was aimed to provide spatial and temporal distribution of the shear stress all along the entire model together with the velocity patterns, related both to the non planar geometry of the aortic system here considered and to the pulsatility imposed on the numerical model to simulate physiologic conditions. A non-Newtonian evolving fluid was considered to account for the actual rheological nature of blood; a comparison on the incidence of wall shear stress, implementing a Newtonian fluid, was also made as reference. The spatial shear stress pattern, within the cardiac cycle, was shown to have higher values in correspondence to the inner wall of the aortic arch and the sites where the major vessels originated from the arch itself. The velocity patterns, on transversal sections of the aorta, resulted in highly skewed morphology. The resulting complex fluid dynamics, established in the aortic arch and in its branches, can be related to the possible endothelium response to mechanical stimuli, induced by wall shear stress, in the promotion of inflammatory events.     

Rheological and cohesive properties of hyaluronic acid

Hyaluronic acid (HA) is a naturally occurring polysaccharide with unique biomedical applications. We have studied the cohesive and rheological properties of HA of three molecular weights (0.35 x 10(6) -1.80 x 10(6) Da) and found that the cohesive nature of HA was highly dependent on molecular weight and solution concentration. To a first approximation, the cohesive nature of HA in solution correlates with concentration, independent of molecular weight. Several rheological parameters correlated with molecular weight: zero shear viscosity, complex viscosity, and the complex viscosity at the crossover point. The cohesive properties of the HA solutions, measured by dynamic aspiration (Poyer et al, J Cataract Refract Surg 1998;24:1130-1135), were found to decrease as the zero shear viscosity increases. The cohesive properties of HA polymer in solution were found to correlate with the high frequency complex viscosity and high frequency loss modulus independent of molecular weight.     

Computational Approach to Estimating the Effects of Blood Properties on Changes in Intra-stent Flow

In this study various blood rheological assumptions are numerically investigated for the hemodynamic properties of intra-stent flow. Non-newtonian blood properties have never been implemented in blood coronary stented flow investigation, although its effects appear essential for a correct estimation and distribution of wall shear stress (WSS) exerted by the fluid on the internal vessel surface. Our numerical model is based on a full 3D stent mesh. Rigid wall and stationary inflow conditions are applied. Newtonian behavior, non-newtonian model based on Carreau-Yasuda relation and a characteristic newtonian value defined with flow representative parameters are introduced in this research. Non-newtonian flow generates an alteration of near wall viscosity norms compared to newtonian. Maximal WSS values are located in the center part of stent pattern structure and minimal values are focused on the proximal stent wire surface. A flow rate increase emphasizes fluid perturbations, and generates a WSS rise except for interstrut area. Nevertheless, a local quantitative analysis discloses an underestimation of WSS for modelisation using a newtonian blood flow, with clinical consequence of overestimate restenosis risk area. Characteristic viscosity introduction appears to present a useful option compared to rheological modelisation based on experimental data, with computer time gain and relevant results for quantitative and qualitative WSS determination.     

Rheological properties of concentrated aqueous injectable calcium phosphate cement slurry

In this paper, the steady and dynamic rheological properties of concentrated aqueous injectable calcium phosphate cement (CPC) slurry were investigated. The results indicate that the concentrated aqueous injectable CPC showed both plastic and thixotropic behavior. As the setting process progressed, the yield stress of CPC slurry was raised, the area of the thixotropic hysteresis loop was enlarged, indicating that the strength of the net structure of the slurry had increased. The results of dynamic rheological behavior indicate that the slurry presented the structure similar to viscoelastic body and the property of shear thinning at the beginning. During the setting process, the slurry was transformed from a flocculent structure to a net structure, and the strength increased. Different factors had diverse effects on the rheological properties of the CPC slurry in the setting process, a reflection of the flowing properties (or injection), and the microstructure development of this concentrated suspension. Raising the powder-to-liquid ratio decreased the distance among the particles, increased the initial strength, and shortened the setting time. In addition, raising the temperature improved the initial strength, increased the order of reaction, and shortened the setting time, which was favorable to the setting process. The particle size of the raw material had much to do with the strength of original structure and setting time. The storage module G' of CPC slurry during the setting process followed the rule of power law function G'=A exp(Bt), which could be applied to forecast the setting time, and the calculated results thereafter are in agreement with the experimental data.