Measurement of blood viscosity using mass-detecting sensor

A newly designed mass-detecting capillary viscometer is extended to measure the viscosity of whole blood over a range of shear rates without the use of anticoagulants in a clinical setting. In the present study as proof of principle, a single measurement of liquid-mass variation with time replaces the flow rate and pressure drop measurements that are usually required for the operation of a capillary tube viscometer. Using a load cell and capillary, we measured the change of mass flowing through capillary tube with respect to the time, m(t), from which viscosity and shear rate were mathematically calculated. For water and adulterated bloods, excellent agreement was found between the results from the mass-detecting capillary viscometer and those from a commercially available rotating viscometer. Also, the mass-detecting capillary viscometer measured the viscosity of unadulterated whole blood without heparin or EDTA. This new method overcomes the drawbacks of conventional viscometers in the measurement of the whole blood viscosity. First, the mass-detecting capillary viscometer can accurately and consistently measure the unadulterated blood viscosity over a range of shear rates in less than 2 min without any anticoagulants. Second, this design provides simplicity (i.e. ease of operation, no moving parts, and disposable) and low cost.     

Theory and design of disposable clinical blood viscometer

A disposable clinical whole blood viscometer which can produce viscosity measures over a wide range of shear rates in a single rapid determination has been developed and is currently under test. The design is based upon the time varying flow of blood through a capillary. The flow is driven by the pressure in a fixed volume air chamber and transmitted to the sample through a compliant membrane. The time varying pressure in the air chamber is measured by a suitable transducer. The instantaneous shear stress of the blood in the capillary is proportional to the air pressure, while the instantaneous shear rate is proportional to the pressure-time derivative. Proper design ensures that the system operates as a first order dynamic system with flow resistance entirely determined by the nonlinear sample viscosity. By constructing the air chamber in two parts coupled by a quick disconnect fitting the design can allow for the blood-containing part of the instrument to be discarded, eliminating handling and cleaning of blood contacted components. The entire determination is completed in less than a minute, so that anticoagulants are not necessary. Tests on a prototype show that the instrument gives results in excellent agreement with those obtained on a cone-plate rheogoniometer.     

High-speed sensing of microliter-order whole-blood viscosity using laser-induced capillary wave

The present paper introduces an innovative contact-free optical viscosity measurement technique, laser-induced capillary wave (LiCW) using pulsed YAG laser as a heating source, to measure whole-blood viscosity with only a microliter-order sample volume and measurement time on the millisecond order. In this method, interfering pulsed laser beams heat a whole-blood sample and generate a capillary wave, the amplitude of which is less than 10 nm with wavelength of 80–100 μm in the present experiment, caused by a spatially sinusoidal temperature distribution. The damped oscillation of the capillary wave, which is detected by a diffracted probing laser beam at the heated area, provides information regarding the viscosity and surface tension of the whole blood. To demonstrate the validity of the present laser-induced capillary wave viscometer, the viscosity of human whole blood taken from two healthy donors having different hematocrit values was measured using 90 μl sample volumes at 37°C. To consider the feasibility of the present technique for blood rheological studies, we discuss the characteristics of LiCW regarding the non-Newtonian behavior of blood, the velocity boundary layer, the existence of a free surface, and the temperature increase of the blood, and also demonstrate the capability of the method to sense the temporal evolution of blood viscosity with sampling frequency of 0.25 Hz.     

急性心肌缺血时低切变率下全血粘度变化机理研究

本实验旨在分析狗急性心肌缺血时低切变率下全血粘度异常升高与红细胞电泳率(EM)和血浆纤维蛋白原浓度变化间的关系。实验结果表明,阻断冠脉血流40min时,低切变率下全血粘度已显著升高,EM明显降低,二者呈高度负相关,此时血浆纤维蛋白原浓度仅轻度增加。缺血时间进一步延长时,EM逐渐恢复,而血浆纤维蛋白原浓度显著升高,此时低切变率下全血粘度升高主要与血浆纤维蛋白原变化有关。     

Perfused transcapillary smooth muscle and endothelial cell co-culture—a novelin vitro model

Summary As mostin vitro endothelial cell (EC)-vascular smooth muscle cell (SMC) co-culture studies have been performed utilizing static culture conditions, none have successfully mimicked the physical environment of these cellsin vivo. EC covering the inner surface of blood vessels are continuously exposed to a hemodynamically imposed mechanical stress resulting from the flow of blood, while SMC are affected by pressure, a flow-related force acting perpendicular to the surface. We have developed a perfused transcapillary co-culture system that permits the chronic exposure of EC and SMC to physiological shear stresses and pressures. SMC and EC co-cultures were successfully established and maintained in long-term culture (7 wk) on an enclosed perfused bundle of semipermeable polypropylene capillaries. By altering flow rate and/or viscosity, shear stresses of 0.07–20 dyn/cm² can be readily achieved in this system. Electron microscopic analysis revealed that SMC formed multilayers around the outside of the capillaries, whereas EC, subjected to 3 dyn/cm² shear stress, formed an intact closely adherent monolayer lining the capillary lumen. EC and SMC exhibited characteristic ultrastructural and gross morphology. EC were separated from SMC by the capillary wall (pore size 0.5 μm, width 150 μM) and while no direct cell-cell contact was evident some cells were seen to migrate into the capillary wall. Both EC and SMC are exposed to the same culture medium, allowing the interaction of substances released in both directions. Yet separate populations of cells are maintained and can be individually harvested for further analysis. This co-culture system that mimics the architecture and physical environment of the vessel wall should have many potential applications in vascular biology.     

3-D computational modeling of media flow through scaffolds in a perfusion bioreactor

Media perfusion bioreactor systems have been developed to improve mass transport throughout three-dimensional (3-D) tissue-engineered constructs cultured in vitro. In addition to enhancing the exchange of nutrients and wastes, these systems simultaneously deliver flow-mediated shear stresses to cells seeded within the constructs. Local shear stresses are a function of media flow rate and dynamic viscosity, bioreactor configuration, and porous scaffold microarchitecture. We have used the Lattice-Boltzmann method to simulate the flow conditions within perfused cell-seeded cylindrical scaffolds. Microcomputed tomography imaging was used to define the scaffold microarchitecture for the simulations, which produce a 3-D fluid velocity field throughout the scaffold porosity. Shear stresses were estimated at various media flow rates by multiplying the symmetric part of the gradient of the velocity field by the dynamic viscosity of the cell culture media. The shear stress algorithm was validated by modeling flow between infinite parallel plates and comparing the calculated shear stress distribution to the analytical solution. Relating the simulation results to perfusion experiments, an average surface shear stress of 5x10(-5)Pa was found to correspond to increased cell proliferation, while higher shear stresses were associated with upregulation of bone marker genes. This modeling approach can be used to compare results obtained for different perfusion bioreactor systems or different scaffold microarchitectures and may allow specific shear stresses to be determined that optimize the amount, type, or distribution of in vitro tissue growth.     

80例TIA病人的血液流变学分析

目的探讨ＴＩＡ病人的血液流变学改变。方法８０例ＴＩＡ病人均在末次发作后２４ｈ内静脉抽血进行血液流变学测定,并与对照组进行比较。结果ＴＩＡ组病人的红细胞压积、全血高切粘度、全血低切粘度、全血还原高切粘度、全血还原低切粘度、血浆粘度及红细胞聚集性各指标均明显增高,与正常对照组比较有显著性差异。结论血液粘度的增高是引起短暂性脑缺血发作的发病机制之一。     

Modeling the mechanical consequences of vibratory loading in the vertebral body: microscale effects

Osteoporosis affects nearly 10 million individuals in the United States. Conventional treatments include anti-resorptive drug therapies, but recently, it has been demonstrated that delivering a low magnitude, dynamic stimulus via whole body vibration can have an osteogenic effect without the need for large magnitude strain stimulus. Vibration of the vertebral body induces a range of stimuli that may account for the anabolic response including low magnitude strains, interfacial shear stress due to marrow movement, and blood transport. In order to evaluate the relative importance of these stimuli, we integrated a microstructural model of vertebral cancellous bone with a mixture theory model of the vertebral body. The predicted shear stresses on the surfaces of the trabeculae during vibratory loading are in the range of values considered to be stimulatory and increase with increasing solid volume fraction. Peak volumetric blood flow rates also varied with strain amplitude and frequency, but exhibited little dependence on solid volume fraction. These results suggest that fluid shear stress governs the response of the vertebrae to whole body vibration and that the marrow viscosity is a critical parameter which modulates the shear stress.     

Effect of plasma exchange on blood viscosity and cerebral blood flow.

The effects of plasma exchange using a low viscosity plasma substitute on blood viscosity and cerebral blood flow were investigated in eight subjects with normal cerebral vasculature. Plasma exchange resulted in significant reductions in plasma viscosity, whole blood viscosity, globulin and fibrinogen concentration without affecting packed cell volume. The reduction in whole blood viscosity was more pronounced at low shear rates suggesting an additional effect on red cell aggregation. Despite the fall in viscosity there was no significant change in cerebral blood flow. The results support the metabolic theory of autoregulation. Although changes in blood viscosity appear not to alter the level of cerebral blood flow under these circumstances, plasma exchange could still be of benefit in the management of acute cerebrovascular disease.     

Mechanical degradation of polyacrylamide solutions as a model for flow induced blood damage in artificial organs

Human or animal blood is normally used as a test fluid for the in vitro evaluation of hemolysis by artificial organs. However, blood has some disadvantages (large biological variability and problems with cleaning the devices). For that reason, we searched for a reproducible technical fluid with blood-like flow characteristics that exhibits similar shear depending destruction. In this study, a direct comparison between erythrocyte damage of bovine blood and shear-induced degradation of polyacrylamide solution is given. A uniform shear field was applied to the fluids using a shear device with a plate-plate geometry. It was shown that similarities exist between erythrocytes disaggregation and breakdown of super molecular structures in polymer solutions, caused by mechanical stress. In both cases steady low shear viscositity was diminished and the elastic component of complex viscosity of blood and polymer solutions has been reduced. There is a correlation between shear-induced hemolysis of bovine blood and mechanical polymer-degradation, which depends on the applied shear stresses.     

Changes in haemorheology in the racing greyhound as related to oxygen delivery

Arterial blood samples were obtained from six greyhounds during rest, immediately before, and after a 704-m (7/16th mile) race. Measurements were made of various haematological (red cell count, haemoglobin, packed cell volume, white cell count, plasma proteins) and haemorheological variables. Blood and plasma viscosity were determined at high wall shear stresses (67-200 dynes.cm-2, 670-2000 microN.cm-2) in a 20-microns glass capillary device which was designed to take the diameter dependence of blood viscosity (Fahraeus-Lindqvist effect) into account. Compared to values at rest, substantial haemoconcentration occurred before the race, mainly due to splenic discharge of red cells. Additional haemoconcentration was found after the race. The increase of effective blood viscosity caused by elevation of packed cell volume was greater than the increase in O2 binding capacity resulting from the elevated haemoglobin concentration, suggesting that the haemoconcentration observed in the exercising greyhound does not enhance O2 delivery to skeletal muscle. The main physiological effect of red cell discharge from the contracting spleen appeared to be a consequence of the volume rather than the composition of the circulating blood.     

The clinical significance of whole blood viscosity in (cardio)vascular medicine

Whole blood is a non-Newtonian fluid, which means that its viscosity depends on shear rate. At low shear, blood cells aggregate, which induces a sharp increase in viscosity, whereas at higher shear blood cells disaggregate, deform and align in the direction of flow. Other important determinants of blood viscosity are the haematocrit, the presence of macro-molecules in the medium, temperature and, especially at high shear, the deformability of red blood cells. At the sites of severe atherosclerotic obstructions or at vasospastic locations, when change of vessel diameter is limited, blood viscosity contributes to stenotic resistance thereby jeopardising tissue perfusion. However, blood viscosity plays its most important role in the microcirculation where it contributes significantly to peripheral resistance and may cause sludging in the postcapillary venules. Apart from the direct haemodynamic significance, an increase in blood viscosity at low shear by red blood cell aggregation is also associated with increased thrombotic risk, as has been demonstrated in atrial fibrillation. Furthermore, as increased red blood cell aggregation is a reflection of inflammation, hyperviscosity has been shown to be a marker of inflammatory activity. Thus, because of its potential role in haemodynamics, thrombosis and inflammation, determination of whole blood viscosity could provide useful information for diagnostics and therapy of (cardio)vascular disease.     

Pulsatile flow in a coronary artery using multiphase kinetic theory

Pulsatile flow in a model of a right coronary artery (RCA) was previously modeled as a single-phase fluid and as a two-phase fluid using experimental rheological data for blood as a function of hematocrit and shear rate. Here we present a multiphase kinetic theory model which has been shown to compute correctly the viscosity of red blood cells (RBCs) and their migration away from vessel walls: the Fahraeus–Lindqvist effect. The computed RBC viscosity decreases with shear rate and vessel size, consistent with measurements. The pulsatile computations were performed using a typical cardiac waveform until a limit cycle was well established. The RBC volume fractions, shear stresses, shear stress gradients, granular temperatures, viscosities, and phase velocities varied with time and position during each cardiac cycle. Steady-state computations were also performed and were found to compare well with time-averaged transient results. The wall shear stress and wall shear stress gradients (both spatial and temporal) were found to be highest on the inside area of maximum curvature. Potential atherosclerosis sites are identified using these computational results.     

血栓通注射液联合阿托伐他汀对急性脑梗死患者血脂和血液流变学的影响

目的:研究阿托伐他汀片与血栓通注射液联合治疗对脑梗死患者血脂及血液流变学的影响。方法:选取我院从2012年2月到2014年2月收治的急性脑梗死患者100例,分成两组,每组各50例。对照组静脉滴注血栓通注射液,试验组静脉滴注血栓通注射液加口服阿托伐他汀片治疗。14天后观察两个组的治疗效果,并且进行血脂(TC、TG、LDL-C、HDL-C)、血液流变学(血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数)等指标的检测,以及疗效及不良反应情况。结果:治疗后试验组TC、TG、LDL-C低于对照组,HDL-C高于对照组,且具有统计学意义(P0.05)。治疗后,试验组血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数均低于对照组,且具有统计学意义(P0.05)。试验组总有效率为88.0%(44/50),高于对照组的66.0%(33/50)(P0.05)。试验组发生不良反应发生率与对照组比较无统计学意义(P0.05)。结论:阿托伐他汀片联合血栓通注射液对于脑梗死患者的血脂和血液流变学的影响疗效显著,且具有明显的降脂效果。     

肠淋巴液引流对失血性休克大鼠红细胞流变性的影响

目的:观察肠淋巴液引流对失血性休克大鼠红细胞流变性指标以及血液黏度的作用。方法:Wistar雄性大鼠均分为假休克组、休克组(复制失血性休克模型)、引流组(复制失血性休克模型,自低血压1 h引流休克肠淋巴液)。在低血压3 h或相应时间,经腹主动脉取血,检测红细胞参数、红细胞电泳、红细胞沉降率(ESR)以及血液黏度,计算红细胞聚集指数、红细胞变形指数。结果:与假休克组比较,休克组红细胞数量、红细胞比积(HCT)、血红蛋白(Hb)、平均红细胞血红蛋白浓度(MCHC)、红细胞电泳率与迁移率、红细胞变形指数、全血黏度、全血低切与高切相对黏度和还原黏度显著降低,休克组平均红细胞体积、红细胞电泳时间、ESR、血沉方程K值与校正K值、红细胞聚集性指数、血浆黏度显著升高;引流组MCHC、红细胞电泳率与迁移率、全血黏度、全血低切与高切还原黏度均显著降低,引流组红细胞体积分布宽度(RDW-SD)显著增加。同时,引流组HCT、RDW-SD、红细胞变形指数、全血黏度、全血低切与高切相对黏度显著高于休克组;ESR、血沉方程K值与校正K值、红细胞聚集性指数、血浆黏度显著低于休克组。结论:休克肠淋巴液引流可改善失血性休克大鼠红细胞流变行为,从而改善血液流变性。     

Degradation of supercoiled plasmid DNA within a capillary device

Supercoiled plasmid DNA is susceptible to fluid stress in large-scale manufacturing processes. A capillary device was used to generate controlled shear conditions and the effects of different stresses on plasmid DNA structure were investigated. Computational fluid dynamics (CFD) analysis was employed to characterize the flow environment in the capillary device and different analytical techniques were used to quantify the DNA breakage. It was found that the degradation of plasmid DNA occurred at the entrance of the capillary and that the shear stress within the capillary did not affect the DNA structure. The degradation rate of plasmids was well correlated with the average elongational strain rate or the pressure drop at the entrance region. The conclusion may also be drawn that laminar shear stress does not play a significant role in plasmid DNA degradation.     

Non-Newtonian rheology of leukemic blood and plasma: are n and k parameters of power law model diagnostic?

When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed.     

Thixotropic properties of whole blood from healthy human subjects

The steady state non-Newtonian viscosity of whole human blood has been widely studied as a function of the shear rate; and used to characterize the blood in various pathological disorders. In our previous studies, we demonstrated that blood is a thixotropic fluid. Its time-dependency and shear rate dependency of rheological behavior can be represented by an equation developed by Huang. Parameters of the equation can be used for the characterization of an individual's blood. They provide information, such as the kinetic rate constant of breakdown of RBC rouleaux to individual erythrocytes and the relative amount of rouleau formation in the dynamic equilibrium between rouleaux and individual erythrocytes. In this communication, the thixotropic parameters from blood samples of fifteen apparently healthy human subjects were investigated. When compared to the use of apparent viscosity values for the correlation with a pathological disorder, thixotropic parameters are preferable. The mean values of thixotropic parameters obtained from apparently healthy human subjects provide a base for comparison with the same parameters as obtained from blood samples of patients with certain pathological disorders involving the circulation.     

Tube flow of human blood at near zero shear

Pressure-velocity relations were obtained in vertical and horizontal glass tubes (I.D. 26 to 83 micron) perfused with normal human blood at feed hematocrits between 0.25 and 0.65. Perfusion pressures used corresponded to wall shear stresses up to 0.27 dyn cm-2. Red cell velocity measurements were made both immediately following implementation of perfusion pressure (with red cells still disaggregated) and in a steady state situation (with red cells aggregated). Analysis of the slopes of the linear relations between perfusion pressure and velocity showed apparent viscosity to decrease with the manifestation of red cell aggregation. In horizontal tubes, sedimentation and aggregation occurred simultaneously, and apparent viscosity increased due to axial asymmetry of cell concentration. Evidence for a yield shear stress (flow stagnation at positive driving pressure) was not observed.     

Detection of red cell aggregation by low shear rate viscometry in whole blood with elevated plasma viscosity

The viscosity of whole blood measured at low shear rates is determined partly by shear resistance of the red cell aggregates present, stronger aggregation increasing the viscosity in the absence of other changes. Effects of cell deformability can confound interpretation and comparison in terms of aggregation, however, particularly when the plasma viscosity is high. We illustrate the problem with a comparison of hematocrit-adjusted blood from type 1 diabetes patients and controls in which it is found the apparent and relative viscosities at a true shear rate of 0.20 s-1 are lower in the patient samples than age matched controls, in spite of reports that aggregation is increased in such populations. Because the plasma viscosities of the patients were higher on average than controls, we performed a series of experiments to examine the effect of plasma protein concentration and viscosity on normal blood viscosity. Dilution or concentration by ultrafiltration of autologous plasma and viscosity measurements at low shear on constant hematocrit red cell suspensions showed (a) suspension viscosity at 0.25 and 3 s-1 increased monotonically with plasma protein concentration and viscosity but (b) the relative viscosity increased, in concert with the microscopic aggregation grade, up to a viscosity of approximately 1.25 mPa-s but above this the value the relative viscosity no longer increased as the degree of aggregation increased in concentrated plasmas. It is suggested that in order to reduce cell deformation effects in hyperviscous pathological plasmas, patient and control plasmas should be systematically diluted before hematocrit is adjusted and rheological measurements are made. True shear rates should be calculated. Comparison of relative viscosities at low true shear rates appears to allow the effects of red cell aggregation to be distinguished by variable shear rate viscometry in clinical blood samples.