Rheology Of Human Blood Research Articles

Characterizing blood hysteresis via tensorial thixo-elasto-viscoplastic modeling

A characteristic feature of human blood rheology is a distinctive stress hysteresis during shear ramp up in the shear rate from zero, followed by a ramp back to zero. This is a result of the fact that human blood has a longer characteristic time of shear-induced rouleaux breakdown compared to the shear aggregation of the rouleaux. We demonstrate this telltale phenomenon of human blood rheology during the triangle ramp, time-dependent change in the shear rate. The unique hysteresis data are then used along with steady state data to fit parameters of a recently published thixo-elasto-viscoplastic rheological model, the tensorial enhanced structural stress thixotropic-viscoelastic (t-ESSTV) model. These best-fit parameter values from the hysteresis ramps are then used to predict step-up/down in shear, small amplitude oscillatory shear, uni-directional large amplitude oscillatory shear, and large amplitude oscillatory shear flow. Additionally, correlations between the calculated fitting parameters and physiological data are analyzed to inform the interpretation of model behavior in physical terms. The fit adherence to the triangle ramp and rheological hysteresis data are then evaluated alongside recently developed techniques to assess thixotropy via hysteresis loop area, indicating the efficacy of the t-ESSTV model in potentially predicting blood's complex characteristics in useful ways for future use in modeling blood flows under a variety of mechanical and biological conditions and predicting pathologies.

Hemorheological alterations of red blood cells induced by 450-nm and 520-nm laser radiation.

Proper rheological properties of red blood cells (RBC) including flexibility and aggregability are essential for healthy blood microcirculation. Excessive RBC aggregation has been observed to be associated with many pathological conditions and is crucial in acute circulatory problems. Low-level laser radiation (LLLR) has been found to have positive effects on the rheology of human blood, however, the detailed mechanisms of blood photobiomodulation remains unclear. In this study, utilizing the single-cell technique optical tweezers (OT) and traditional light microscopy, the influence of photobiomodulation of human RBC was examined under different conditions of laser irradiation. The results revealed that high radiant exposure (over 170.5J/cm2 radiant fluence) caused enhanced RBC aggregation and cell shape transformation while the aggregation force between single RBC remained unchanged. LLLR with radiant fluence below 9.5J/cm2 by 450nm wavelength improved the RBC deformability, weakened the strength of cell-cell interaction in the RBC disaggregation process, and showed rejuvenating effects on RBC suspended in a harsh cell environment.

Recent advances in blood rheology: a review

Due to the potential impact on the diagnosis and treatment of various cardiovascular diseases, work on the rheology of blood has significantly expanded in the last decade, both experimentally and theoretically. Experimentally, blood has been confirmed to demonstrate a variety of non-Newtonian rheological characteristics, including pseudoplasticity, viscoelasticity, and thixotropy. New rheological experiments and the development of more controlled experimental protocols on more extensive, broadly physiologically characterized, human blood samples demonstrate the sensitivity of aspects of hemorheology to several physiological factors. For example, at high shear rates the red blood cells elastically deform, imparting viscoelasticity, while at low shear rates, they form "rouleaux" structures that impart additional, thixotropic behavior. In addition to the advances in experimental methods and validated data sets, significant advances have also been made in both microscopic simulations and macroscopic, continuum, modeling, as well as novel, multiscale approaches. We outline and evaluate the most promising of these recent developments. Although we primarily focus on human blood rheology, we also discuss recent observations on variations observed across some animal species that provide some indication on evolutionary effects.

Application of population balance-based thixotropic model to human blood

Modeling blood rheology remains challenging in part because of its multiphase, aggregating colloidal nature that gives rise to complex viscoplastic and time-dependent (thixotropic) behavior. Here, we demonstrate that a multiscale approach incorporating a direct coupling of coarse-graining particle-level modeling to the macroscopic phenomenological modeling can provide new insights and a promising methodology. Specifically, a general population balance-based, multiscale, thixotropic modeling approach, first proposed by Mwasame et al., AIChE J. 63 (2017) 517–531, is applied to account for the rouleaux-induced thixotropy in human blood in shear flow. Population balances offer a compelling alternative to previously proposed structure-based heuristic kinetics models of aggregating colloidal suspensions as they use a statistical approach to describe the aggregate size distribution with well-defined processes for either shear-induced or Brownian aggregation and breakup under shear flow. When applied to human blood, the population balance approach offers a first attempt to model the size evolution of predominantly coin-stack like rouleaux structures of the red blood cells that are the primary source behind the observed yield stress and thixotropy of blood at low shear rates. This microscopic information, suitably coarse-grained, is then introduced into a semi-phenomenological macroscopic model that expresses the total stress in terms of an elastic and viscous contribution. Shear thinning introduced due to the red blood cell deformation at high shear rates is accounted for by following Horner et al., J. Rheol. 62 (2018) 577–591. An advantage of this modeling approach is that the parameters have specific physical meaning that allows for independent estimates and/or evaluations through appropriately designed independent experiments. Conversely, parameters with specific microscopic interpretations, such as the fractal dimension of the aggregates, df, are obtained fits of macroscopic shear experiments. Fitting and predictions use steady shear, and unidirectional large amplitude oscillatory shear (UD-LAOS) experiments on whole blood samples of two healthy donors, as reported in Horner et al. We obtain values for df in the range of 1.5 ± 0.2 which is consistent with the rod-like shape of rouleaux structures reported in the literature. Furthermore, the shear predictions compare favorably against the experiments. While this approach is not as accurate as the fits of prior structure kinetics modeling of Horner et al., these promising results provide a pathway for model improvement by including independently verified physical properties of blood. This work demonstrates a new particle-level approach for describing and predicting the non-Newtonian, thixotropic rheology of human blood.

Investigation of blood rheology under steady and unidirectional large amplitude oscillatory shear

We present new dynamic rheological tests of human blood that motivate an improved model for the thixotropic shear rheology of human blood. Unidirectional large amplitude oscillatory shear (UD-LAOS) is proposed as a dynamic test relevant for understanding in vivo arterial pulsatile blood flow, and data are presented for two healthy donors studied previously using more traditional steady and step-rate experiments. The model analyzes the overall extra stress of the system in two components. A thixotropic component is represented by a structure-kinetics model coupled with a stress expression containing both viscoelastic and thixotropic elements to account for the presence of linear aggregates of red blood cells, known as rouleaux, which form at low shear rates. Another component is viscoelastic, described through an extend White–Metzner approach. It corresponds to the stresses that arise due to the isolated red blood cells, which deform at high shear rates. The combined model is fit to experimental steady shear and UD-LAOS data for two healthy donors and is subsequently used to predict the stress response of the blood sample to UD-LAOS experiments over a broad range of strain amplitudes and frequencies. Comparison to the previous models for transient blood rheology shows a significantly improved fit over a range of physiologically relevant flow conditions. In addition, this analysis demonstrates the usefulness of UD-LAOS tests with regards to understanding the microstructural evolution in blood under transient flow. We present new dynamic rheological tests of human blood that motivate an improved model for the thixotropic shear rheology of human blood. Unidirectional large amplitude oscillatory shear (UD-LAOS) is proposed as a dynamic test relevant for understanding in vivo arterial pulsatile blood flow, and data are presented for two healthy donors studied previously using more traditional steady and step-rate experiments. The model analyzes the overall extra stress of the system in two components. A thixotropic component is represented by a structure-kinetics model coupled with a stress expression containing both viscoelastic and thixotropic elements to account for the presence of linear aggregates of red blood cells, known as rouleaux, which form at low shear rates. Another component is viscoelastic, described through an extend White–Metzner approach. It corresponds to the stresses that arise due to the isolated ...

Contemporary modeling and analysis of steady state and transient human blood rheology

The rheological characterization of a human blood, through modeling and analysis of transient flows and large-amplitude oscillatory shear (LAOS) flow, has made tremendous progress recently. We show how various components, and modifications of two recent scalar, structural kinetic, thixotropic models, can offer several modeling and prediction improvements, and compare our results to the Maxwell-like Bautista-Manero-Puig (BMP) model, and a recent transient model based on the Herschel-Bulkley. We explore the weakness of the legacy blood models, and then, we apply this newly improved model to recently published data from the literature in order to demonstrate its efficacy in modeling steady state, transient, and oscillatory shear flow. Following this effort, we demonstrate a novel approach using the sequence of physical phenomena (SPP) to facilitate interpretation, characterization, mapping, and “fingerprinting” of transient blood data from the literature. We compare the SPP approach to other LAOS analysis techniques in the literature and show how our approach can function as a mechanical-property diagnostic blood analysis tool. The goal of this work is a deeper understanding of the microstructural basis and validity of structural thixotropic blood models, and transient flow analysis techniques and procedures.

The application of silicon sol–gel technology to forensic blood substitute development: Mimicking aspects of whole human blood rheology

Solution–gelation chemistry has promising applications in forensic synthetic blood substitute development. This research offers a silicon-based sol–gel approach to creating stable materials that share similar rheological properties to that of whole human blood samples. Room temperature, high water content, silicon sol–gels were created using the organosilane precursors 3-glycidoxypropyltrimethoxysilane and tetraethylorthosilicate along with various concentrations of filler and pigment. Shear-thinning non-Newtonian properties were observed within most formulations of the presented materials. The effects of colloidal concentration, temperature, age and filler addition on the viscosity of the sol–gels were investigated. SEM–EDS analysis was used to identify the behavior of the fillers within the film and support their inclusion for basic bloodstain pattern simulation. A final proposed candidate sol–gel was assessed using a previously reported passive drip simulation test on a hard, dry surface and passed. This works represents encouraging development in providing safe material alternatives to using whole human blood for forensic training and research.

Modeling of human blood rheology in transient shear flows

We offer here an extension of our previous work [Apostolidis and Beris, J. Rheol. 58, 607–633 (2014)] of modeling blood flow rheology in simple shear steady state flows to time-dependent conditions. The basis of our model is a scalar, structural, parameter thixotropic model. More specifically, we show that a modified version of the “Delaware model” [A. Mujumdar et al., J. Non-Newtonian Fluid Mech. 102, 157–178 (2002)] is capable of predicting the time-dependent shear flow rheology of blood at low and moderate values of shear rate. At steady state, the model reduces to the Casson constitutive model for low and moderate shear rate values consistent to the findings of our previously mentioned work. At high shear rates it reduces to a Newtonian model, correcting our previous model and consistent to data from the literature [Merrill and Pelletier, J. Appl. Physiol. 23, 178–182 (1967)]. Exploiting the existing parameterization developed before for the steady state Casson model and the Merrill and Pelletier steady state data, the transient thixotropic model introduces only three additional parameters. Each one of these parameters has a specific physical meaning: A zero-shear rate maximum strain, and two kinematic parameters governing the relaxation of the structural parameter and the elastic modulus, respectively. The model is able to naturally account for the additional yield strengthening effect attributable to the red blood cell rouleaux structures developed within blood. The proposed model can fit excellently the experimental data of Bureau et al. [Biorheology 17, 191–203 (1980)], on simple triangular steps in shear flow at low shear rates. The predictions of the present model are then validated comparing them against additional experimental data, collected on the same samples, either on triangular steps in shear flow but at higher shear rates or on rectangular step-up and step-down experiments. The model is further validated by comparing its predictions against recent large amplitude oscillatory shear data [P. C. Sousa et al., Biorheology 50, 269–282 (2013)]. In all these comparisons there is good, at least semiquantitative, agreement, with the observed discrepancies only appearing at the higher shear rates, where the isotropic description resulting from the use of a single scalar internal parameter to describe the blood microstructure naturally breaks down.

Change whole human blood rheology as a prediction factor of cardiac sudden death on a man taking Japanese style bath

Change whole human blood rheology as a prediction factor of cardiac sudden death on a man taking Japanese style bath

Effects of Astaxanthin on Human Blood Rheology

Effects of astaxanthin (AX) derived from H. pluvialis on human blood rheology were investigated in 20 adult men with a single-blind method. The experimental group was 57.5 ± 9.8 years of age and the placebo group was 50.8 ± 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer). After administration of AX 6 mg/day for 10 days, the values of the experimental group were decreased from 52.8 ± 4.9 s to 47.6 ± 4.2 s (p<0.01) and a comparison of the values between the experimental (47.6 ± 4.2 s) and the placebo (54.2 ± 6.7 s) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6 mg/day for 10 days. Informed consent was obtained from each subject.

Effects of Astaxanthin on Human Blood Rheology

Effects of astaxanthin derived from Haematococcus pluvialis (AX) on human blood rheology were investigated in 20 adult Japanese men with a single-blind method. The experimental group (n=10) was 57.5 ± 9.8 years of age and the placebo group (n=10) was 50.8 ± 13.1 years of age. A blood rheology test that measures whole blood transit time was conducted using heparinized blood of the volunteers by a MC-FAN apparatus (microchannel array flow analyzer, bloody 6–7; 8736 channels; width 7 micrometer, length 30 micrometer, depth 4.5 micrometer; Hitachi Haramachi Electronics Co., Ltd.). After administration of AX 6mg/day for 10 days, the values of the experimental group were decreased from 52.8 ± 4.9 sec to 47.6 ± 4.2 sec (p<0.01) and a comparison of the values between the experimental (47.6 ± 4.2 sec) and the placebo (54.2 ± 6.7 sec) groups showed a significant difference (p<0.05). There were no adverse effects resulting from the administration of AX 6mg/day for 10 days. Informed consent was obtained from each subject. This study complied with the Declaration of Helsinki.

Hemodynamic evaluation with TURBO BRISK – a rapid phase contrast angiography technique

Hemodynamic imaging by phase contrast angiography was significantly accelerated by selective interpolation and segmentation in k-space using TURBO BRISK. The method was tested in vitro on three independent flowfields, representative of human blood rheology: a straight tube simulating the descending aorta, a curved tube simulating the aortic arch and a two-chamber orifice flow model simulating valvular regurgitation. The results were compared to data obtained by Laser Doppler Velocimetry (LDV) and showed good agreement. For the straight tube, the flow velocity obtained by five TURBO BRISK methods with increasing segmentation factors and corresponding time savings showed good agreement with LDV. For the curved tube, the velocity showed good general agreement with some differences in the decelerating part of the cycle, and in the low-velocity secondary flow structures. The orifice flow evaluation, the most time consuming case, was performed by the control volume method. It showed good agreement with actual flows through the orifice. Data acquisitions for TURBO-4 BRISK could be performed in 20s for each velocity component. The method shows promise for breath-hold acquisitions in clinical applications, including calculation of blood flow volumes through diseased arteries, measurement of blood backflow volumes through dysfunctional heart valves to time valve replacement operations, and evaluation of arterial wall shear stress, an important factor in the genesis of atherosclerosis.

Is There a Case for Haemorheological Screening in the Haemocompatibility Testing of Materials?

Bio-interactions between a material and blood govern the compatibility of the material with the human body and, therefore, the single most important requirement for the blood interfacing implants/devices is haemocompatibility. The decisive events which control haemocompatibility occur at the molecular level and affect the various subphases of blood rheology. This effect on the already complex human blood rheology can be used to our advantage in the screening of blood-contacting materials. An attempt has been made in the present work to evaluate the haemocompatibility of materials based on changes in microrheological parameters of human blood. Samples of materials of equal surface area known to be haemocompatible (medical grade silicon, polyvinyl chloride from blood bags) and materials known to be extremely haemo-incompatible (pyrex glass, copper, cotton fabric, all commercial grade) were incubated at 37.4 degrees C in freshly drawn anticoagulated whole human blood, and changes in the haemorheological parameters (whole blood, plasma viscosity, intrinsic viscosity of red cells, platelet aggregation, albumin fibrinogen ratio) have been evaluated. The results of the study show that alterations in the haemorheological parameters are reliable indicators to the compatibility/incompatibility characteristics of well-known substances and that there is a case for haemorheological screening of biomaterials in the overall framework of haemocompatibility tests.

Effect of Hematocrit on Nonlinear Oscillations of Bubbles in Blood.

The equation of motion for a bubble in blood subjected to an oscillating pressure is derived by using a modified Casson model, which well represents the rheology of human blood. The natural frequency of a bubble is approximately obtained. According to computational analyses, the frequency response curves for bubble ocsillation in blood are delineated. As a result, the values of nondimensional amplitude in the neighborhood of primary resonance and harmonic resonance increase with decreasing in hematocrit of blood. It is found that the amplitude of oscillation of the bubble decreases with an increase of hematocrit, and that the pressure produced during the bubble shrinkage lowers with a decrease of hematocrit.

Time-dependent rheological behaviour of blood flow at low shear in narrow horizontal tubes.

Magnitude and time-dependence of the effects of red cell aggregation and sedimentation on the rheology of human blood were studied during low shear (tau W 2.5 to 92 mPa) flow through horizontal tubes (ID 25 to 105 microns). Immediately following reduction of perfusion pressure to a low value the red cell concentration near the tube walls decreases as a result of red cell aggregation. This is associated with a transient increase of centerline velocity. Simultaneously, sedimentation begins to occur and eventually leads to the formation of a cell-free supernatant plasma layer. Time-course and extent of this sedimentation process are strongly affected by wall shear stress variation, particularly in the larger tubes. At the lower shear stresses, centerline velocity decreases (flow resistance increases) with time following the initial acceleration period, due to sedimentation of red cells. This is followed by a further increase of resistance caused by the elevation of hematocrit occurring because of the reduction of cell/plasma velocity ratio. The time dependence of blood rheological behaviour under these flow conditions is interpreted to reflect the net effect of the partially counteracting phenomena of sedimentation and red cell aggregation.

Hypothyroidism and the influence on human blood rheology.

Viscoelastic properties of human whole blood were measured in 338 subjects: 110 persons (75 F, 35 M) following total thyroidectomy but without substitution therapy over three weeks as well as 228 healthy control subjects (124 F, 104 M) were investigated in this study. Subjects with other variable factors were excluded. The viscous and the elastic portion of apparent whole blood viscosity -the latter subdivided into red cell aggregation and red cell rigidity were determined by using a newly developed oscillating capillary rheometer and densitymeter at the real hematocrit value and at a computed hematocrit of 40%. Serum viscosity, hematocrit (Hct), hemoglobin (Hb), mean corpuscular volume of red blood cells (MCV), free triiodothyronine (fT3), free thyroxine (fT4) and serum-thyrotropin (bTSH) were evaluated as well. In a further subgroup of 80 subjects (40 patients with hypothyroidism, 40 healthy control persons) additional plasma viscosity and sedimentation rate were determined. Red cell aggregation and blood viscosity especially at shear-rates below 10/sec increased significantly in hypothyroid patients. There was no significant difference of red cell rigidity, serum viscosity, plasma viscosity and sedimentation rate as against euthyroids. So new aspects of thyroid dysfunction could be described probably with consequences for therapy and for considerations about the development of atherosclerosis and ischemic disorders.

Effect of low fibrinogen concentrations on the rheology of human blood in vitro

The influence of low concentrations of fibrinogen on the rheology of normal human blood was investigated with an instrument that permitted simultaneous determination of viscosity and the state of red blood cell aggregation and deformation. Fibrinogen, in concentrations of 9-82 mg/100 ml, decreased blood viscosity at all shear rates below the value obtained with red blood cells suspended in serum. At concentrations above 116 mg/100 ml viscosity was increased. Aggregate formation increased progressively as the fibrinogen concentration increased, necessitating higher dispersing shear rates. The deformation and alignment of the red cells, occurring at a shear rate of 230 s-1, was facilitated by low concentrations. The effect of fibrinogen on low-shear viscosity is explained by the formation of different kinds of aggregates. At low concentrations, the aggregates consist of only few cells forming spherelike particles displaying hemodynamic properties better than those of the single discoid cells. At normal or high concentrations big rodlike aggregates occur and increase resistance to flow.

Shear-dependent deformation of erythrocytes in rheology of human blood.

Shear-dependent deformation of erythrocytes in rheology of human blood.

Influence of anaesthetics in rheology of human blood.

Cyclopropane, halothane, and methoxyflurane were investigated for their effects on the viscometry of freshly drawn human blood (group O, Rh+). A total of 43 blood and 63 plasma samples containing specific anaesthetic agents were studied under controlled conditions of temperature, pH, Pco2, Po2, and red blood cell and plasma protein concentrations. A series of three cone plate viscometers, each with different shear rate ranges from 1500 to 6.75 sec.-1, was used. The Casson viscosity of blood and apparent plasma viscosity were determined from the slope of the shear stress-shear rate relationship plotted on a square root scale. Yield stress was determined by extrapolation from the shear stress axis intercept. Our findings indicate that the three anaesthetic agents, within concentrations equivalent to those used during clinical anaesthesia, caused no discernible effect on either yield stress or the apparent viscosity of blood or plasma. However, there was a marginal increase of the yield stress of blood with high concentrations of cyclopropane (above 20 mg.%) and a trend toward reduced plasma viscosity in all of the methoxyflurane samples.

Influence of plasma osmolarity on the rheology of human blood.

Influence of plasma osmolarity on the rheology of human blood.