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Deformability of red blood cells: A determinant of blood viscosity
Abstract
The suspension of hardened red blood cells (RBCs) differs from the suspension of normal RBCs with respect to their rheological
behavior. The present study investigated the effect of deformability of RBCs on blood viscosity. RBC deformability and blood
viscosity were measured with a recently developed slit-flow laser-diffractometer and the pressure-scanning capillary viscometer,
respectively. At the same level of cell concentration, the viscosity of the hardened RBC suspension is higher than that of
the normal RBCs suspension. An increase in cell percentage for hardened RBCs shows the significant increase in the level of
blood viscosity compared to the normal RBCs. In addition, it was found that RBC deformability played an important role in
reducing viscosity at low shear rates as well as high shear rates. These results present the evidence for the effect of RBC
deformability on blood viscosity using newly developed methods, which can be used in early diagnosis of the cardiovascular
diseases.
... However, the double reciprocal plot distorts the error structure of the data fit and, therefore, is not the most accurate tool for representing kinetics (Greco et al. 1979) or any other processes, From the fitted deformability curves all parameters such as: SS at one half maximal value of deformability curve (½ SS), value of EI at one half maximum of deformability curve (½ EI), value of EI at the pressure of 3 Pa and dEI / dSS also at one half maximal value of deformability curve was determined. The definition of EI is given in Eq. 1. (Shin et al. 2005a). EI is calculated from the diffraction images at the specific SS. ...
Comparative analysis of erythrocyte deformability in individuals with Diabetes Mellitus (DM) and healthy individuals (Control) was represented, focusing on the Elongation index (EI) calculation based on diffraction images. While no statistically significant differences in EI values were observed between the groups, we determined specific points along the deformability curve and revealed the first derivative of deformability curve (dEI / dSS) as a potential metric for quantifying erythrocyte response to deformation, where SS represents shear stress in Pa (Pascal). Statistically significant differences in dEI / dSS at the half maximum value of the deformability curve were identified, suggesting a slower erythrocyte response to shear stress in DM patients. Scatter plot analysis demonstrated a linear declining trend in dEI / dSS index with an increase in shear stress, indicating decaying erythrocyte responsiveness to higher shear stress values, particularly pronounced in DM patients. Although pilot, this study suggests that dEI / dSS can provide valuable insights into the hemorheological aspects of DM pathology and contribute to a comprehensive understanding of erythrocyte mechanobiological behavior in response to varying shear stress levels. Correlations between the proposed measure of RBC mechanical properties and established clinical markers of DM and its complications (serum cholesterol, creatinine, and urea level) are obtained to get preliminary insight into dEI / dSS application for better diagnosis and/or patient management.
... Assessing of rheological changes in the RBC features plays a key role in understanding complex pathophysiological processes affecting the microcirculation in preeclampsia. The main manifestation of PE-hypertension is associated with abnormalities in blood viscosity [49], which strongly depends on the aggregation and deformability of red blood cells [50]. ...
Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity.
... The deformation of red blood cells under the shear stress generated in the microchannel causes elongation of the diffraction pattern in the direction perpendicular to cell stretching. The EIdefined as the ratio of the difference between the long and short axes to their sum [54], characterizes the ability of red blood cells to deform when passing through capillaries and thin blood vessels [55]. ...
Krew, z fizycznego punktu widzenia, to układ wielofazowy oraz wieloskładnikowy; osocze jest fazą zwartą, a elementy morfotyczne są fazą rozproszoną. Aby określić prawidłowe właściwości reologiczne konieczna jest analiza prędkości przepływu. Podczas wolnego przepływu może dochodzić do wzrostu agregacji krwinek, za co odpowiadają fibrynogen oraz globuliny. Ważna jest także odkształcalność krwinek czerwonych, szczególnie podczas przepływu przez naczynia włosowate, gdzie muszą się dostosować do mniejszej średnicy naczyń. Lepkość określa się jako wewnętrzny opór przepływu; jeśli będziemy rozpatrywać krew jako składową dwóch warstw, które są równoległe, to lepkość opisywana jest przez tarcie dwóch sąsiadujących ze sobą warstw. Warstwy cieczy przemieszczają się z różną prędkością równolegle względem siebie i powstaje gradient prędkości (szybkość ścinania). Aby go wytworzyć, potrzebna jest siła poruszająca warstwy, określana jako naprężenie ścinające. Agregaty z krwinek są obserwowane zarówno fizjologicznie, jak i w przebiegu niektórych chorób, takich jak choroba niedokrwienna serca, zawał mięśnia sercowego i miażdżyca. Wyróżnia się dwa rodzaje czynników sprzyjających tworzeniu się agregatów: zewnętrzne – stężenie białek osocza, hematokryt oraz siły ścinania, i wewnętrzne, które stanowią kształt i odkształcalność erytrocytów oraz właściwości błony komórkowej. Przy hiperfibrynogenemii wzrasta agregacja erytrocytów, lepkość osocza i opór mikronaczyniowy. Laserowo-optyczny rotacyjny analizator krwinek czerwonych ( laser-assisted optical rotational cell analyzer – LORCA) służy do badań odkształcalności oraz agregacji erytrocytów. Łączy techniki sylektometrii z ektacytometrią. Tworzenie się trójwymiarowej struktury krwinek czerwonych ma istotny wpływ na pomiar lepkości krwi oraz przepływu krwi przy niskiej prędkości ścinania. stanowią: kształt i odkształcalność erytrocytów oraz właściwości błony komórkowej. Przy hiperfibrynogenemii wzrasta agregacja erytrocytów, lepkość osocza i opór mikronaczyniowy. Laserowo-optyczny rotacyjny analizator krwinek czerwonych służy do badań odkształcalności oraz agregacji erytrocytów. Łączy techniki sylektometrii z ektacytometrią. Tworzenie się trójwymiarowej struktury krwinek czerwonych ma istotny wpływ na pomiar lepkości krwi oraz na przepływu krwi przy niskiej prędkości ścinania.
... One of the main rheological characteristics of blood is the deformability of erythrocytes, which is defined as a measure of the ability of blood cells to change their shape under the action of external forces [1][2][3][4]. ...
... It is crucial for the quality of microcirculation and the delivery of oxygen to all tissues within the human body. At the same time, the deformability of RBCs is important for their survival within the circulation and responsible for the decrease in blood viscosity, especially at higher shear rates [1]. Reduced deformability of RBCs plays a significant role in the etiology of various diseases including cardiovascular, and also during physiological aging [2,3]. ...
Erythrocyte deformability, crucial for oxygen delivery to tissues, plays an important role in the etiology of various diseases. As the factor maintaining the erythrocyte deformability, nitric oxide (NO) has been identified. Reduced NO bioavailability also plays a role in the pathogenesis of hypertension. Our aim was to determine whether aging and hypertension affect erythrocyte deformability and NO production by erythrocytes in experimental animals divided into six groups according to age (7, 20 and 52 weeks), labeled WKY-7, WKY-20 and WKY-52 for normotensive Wistar-Kyoto (WKY) rats, and SHR-7, SHR-20 and SHR-52 for spontaneously hypertensive rats (SHR). The filtration method for the determination of erythrocyte deformability and the fluorescent probe DAF-2 DA for NO production were applied. Deformability and NO production by erythrocytes increased at a younger age, while a decrease in both parameters was observed at an older age. Strain-related differences in deformability were observed at 7 and 52 weeks of age. SHR-7 had reduced deformability and SHR-52 had increased deformability compared with age-matched WKY. Changes in NO production under hypertensive conditions are an unlikely primary factor affecting erythrocyte deformability, whereas age-related changes in deformability are at least partially associated with changes in NO production. However, an interpretation of data obtained in erythrocyte parameters observed in SHRs of human hypertension requires precaution.
... Neutrophil extracellular traps (NET) are an antimicrobial mechanism of neutrophilic granulocytes. Their main component is extracellular DNA that is associated with antimicrobial proteins [52]. NETosis is a type of cell death dependent on the formation of NETs. ...
Stroke constitutes the second highest cause of morbidity and mortality worldwide while also impacting the world economy, triggering substantial financial burden in national health systems. High levels of blood glucose, homocysteine, and cholesterol are causative factors for atherothrombosis. These molecules induce erythrocyte dysfunction, which can culminate in atherosclerosis, thrombosis, thrombus stabilization, and post-stroke hypoxia. Glucose, toxic lipids, and homocysteine result in erythrocyte oxidative stress. This leads to phosphatidylserine exposure, promoting phagocytosis. Phagocytosis by endothelial cells, intraplaque macrophages, and vascular smooth muscle cells contribute to the expansion of the atherosclerotic plaque. In addition, oxidative stress-induced erythrocytes and endothelial cell arginase upregulation limit the pool for nitric oxide synthesis, leading to endothelial activation. Increased arginase activity may also lead to the formation of polyamines, which limit the deformability of red blood cells, hence facilitating erythrophagocytosis. Erythrocytes can also participate in the activation of platelets through the release of ADP and ATP and the activation of death receptors and pro-thrombin. Damaged erythrocytes can also associate with neutrophil extracellular traps and subsequently activate T lymphocytes. In addition, reduced levels of CD47 protein in the surface of red blood cells can also lead to erythrophagocytosis and a reduced association with fibrinogen. In the ischemic tissue, impaired erythrocyte 2,3 biphosphoglycerate, because of obesity or aging, can also favor hypoxic brain inflammation, while the release of damage molecules can lead to further erythrocyte dysfunction and death.
... One of the important rheological characteristics of blood is the deformability of erythrocytes, which is defined as a measure of the ability of these cells to change their shape under the action of external forces [1][2][3][4][5]. Measurement of this parameter is important in the diagnosis and treatment of sickle cell anemia [6], tropical malaria [7], hereditary spherocytosis [8], and many other diseases. ...
... where is the domain occupied by the blood ow, which re ects the action of the uid on the cell membranes. In the FSI model, the mechanical behavior F c of RBCs is coupled into the blood ow by introducing a new force f S such that each RBC is allowed to be treated as an independent object to explore its behavior, such as deformation (Shin et al., 2005;Barber et al., 2008;and Tomaiuolo et al., 2009), aggregation (Liu and Liu, 2006;Barber et al., 2011;and Mehri et al., 2018), cell-free layer (Kim et al., 2007(Kim et al., , 2009Zhang et al., 2009;and Balogh and Bagchi, 2019), and so on. Hence, in the cellularscale modeling, the mixture theory considers the cell population as the other non-Newtonian uid, while the FSI model considers individual and elastic cells that are immersed into the uid, including the non-Newtonian behavior. ...
This book provides updates for a broad range of applications based on recently developed relationships between suspension mechanics and interparticle interactions, particle-particle contact, suspending medium rheology, flow regime, and solute mixing rates. It provides a base understanding of colloidal hard sphere rheology as a foundation for the remaining chapters. It concludes with an explanation of the intimate connection between the rheology of a suspension and its solute mass transfer characteristics.
Recent Advances in Rheology: Theory, Biorheology, Suspension, and Interfacial Rheology is written by top scientists in the field and:Provides in-depth and state-of-the-art coverage of this specialized topicUpdates the field of rheology as applied to medical, polymer, food, cosmetics, coating, surfactant, petroleum extraction, and processing applicationsIncludes updates on suspension and interfacial rheology
Suitable for physicists, applied mathematicians, physical chemists, and engineers in academia and industry, this book is an important and timely resource.
... It is interesting that these correlations are directly opposite to the correlations of these parameters with blood macrorheology in large vessels. An increase in the number of RBCs in the blood, its hematocrit and hemoglobin concentration increase blood viscosity, which leads to a deterioration in its macrorheology in large vessels [15][16][17]. On the other hand, a higher count of RBCs, Hct and Hb should be observed in the blood of patients whose RBCs were not subjected to strong influences and destruction as a result of the pathological process. ...
For the first time, the influence of COVID-19 on blood microrheology was studied. For this, the method of filtering erythrocytes through filters with pores of 3.5 μm was used. Filterability was shown to significantly decrease with the increasing severity of the patient's condition, as well as with a decrease in the ratio of hemoglobin oxygen saturation to the oxygen fraction in the inhaled air (SpO2/FiO2). The filterability of ≤0.65, or its fast decrease during treatment, were indicators of a poor prognosis. Filterability increased significantly with an increase in erythrocyte count, hematocrit and blood concentrations of hemoglobin, albumin, and total protein. The effect of these parameters on the erythrocyte filterability is directly opposite to their effect on blood macrorheology, where they all increase blood viscosity, worsening the erythrocyte deformability. The erythrocyte filterability decreased with increasing oxygen supply rate, especially in patients on mechanical ventilation, apparently not due to the oxygen supplied, but to the deterioration of the patients' condition. Filterability significantly correlates with the C-reactive protein, which indicates that inflammation affects the blood microrheology in the capillaries. Thus, the filterability of erythrocytes is a good tool for studying the severity of the patient's condition and his prognosis in COVID-19.
Red blood cell (RBC) preservation is very important in human health. The RBCs are usually preserved at 4 ± 2 °C without freezing or at a very low temperature (-80 °C or liquid nitrogen) with deep freezing. Herein, non freezable preservation of RBCs at a subzero temperature is reported to prolong the preservation time compared with that at 4 ± 2 °C. By adding glycerol and poly(ethylene glycol) (PEG) (average number molecular weight 400, PEG-400) into the preservation solution, the freezing point is decreased and the hemolysis is kept low. The cell metabolism of stored RBCs at -8 °C is reduced, and the shelf life of RBCs extends up to at least 70 days. At the end of preservation, the pH decreases a little bit to demonstrate the low metabolic rate of RBCs stored at subzero temperatures. After quick washing, the RBC survival rate is ca. 95%. The adenosine triphosphate, 2,3-diphosphoglycerate, and cell deformation ability of the washed RBCs are maintained at a high level, while the malondialdehyde is relatively low, which verifies the high quality of RBCs stored at this condition.
The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser-assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deformability and aggregation, demonstrating the practical versatility of this instrument in the field of hemorheology.
A newly designed pressure-scanning slit viscometer is developed to combine an optical device without refraction while measuring
blood viscosity over a range of shear rates. The capillary tube in a previously designed capillary viscometer was replaced
with a transparent slit, which is affordable to mount optical measurement of flowing blood cells. Using a pressure transducer,
we measured the change of pressure in a collecting chamber with respect to the time, p(t), from which the viscosity and shear
rate were mathematically calculated. For water, standard oil and whole blood, excellent agreement was found between the results
from the pressure-scanning slit viscometer and those from a commercially available rotating viscometer. This new viscometer
overcomes the drawbacks of the previously designed capillary viscometer in the measuring whole blood viscosity. First, the
pressure-scanning slit viscometer can combine an optical instrument such as a microscope. Second, this design is low cost
and simple (i.e., ease of operation, no moving parts, and disposable).
Deformation of the erythrocyte membrane by the micropipette technique permits analysis of intrinsic material characteristics of the membrane and provides a means to differentiate purely membrane factors from such extrinsic factors as surface area-to-volume ratio. Using small micropipettes (less than 0.5 microns radius) to deform cells, it is evident that the red cell membrane behaves like a solid for periods of time up to 5–10 min of sustained deformation; for long periods of strain, permanent deformations occur, indicative of the semi-solid structural character. In the time range in which the membrane behaves like a solid, the material is linearly elastic up to strains of 400%, implying a loose network structure in the membrane plane, and evaluation of the elastic parameter mu (mu for normal discocytes equals 7 x 10(-3) dynes/cm) suggests that the elements comprising the network may have a molecular weight of approximately that of the water-soluble membrane protein spectrin. Whether the network system is cross-linked or simply a polymer solution remains unanswered. Experimental data indicate that plastic flow of the membrane under conditions of protracted strain may lead to permanent deformation of the membrane, whereas uniform dilation of the membrane, requiring over 1000 times more energy than for plastic flow, results in membrane failure and lysis. Analyses of the data from larger micropipettes of limiting mean cylindrical diameter show their utility in evaluating extrinsic factors, e.g., surface area-to-volume relationships, which are related to the capability of the whole cell to form a new configuration with implicit resistance to total surface area change, as the cell enters narrow channels of the microcirculation. Thus, micropipettes with diameters in the 2.7–3.0-microns range can provide sensitive comparisons of cellular deformability of erythrocytes.
Blood rheology is the study of the flow behaviour of blood. Twenty years ago, John Dormandy showed that increased blood viscosity (its resistance to flow in wide vessels) was associated with decreased leg blood flow (Dormandy 1971), with intermittent claudication (Dormandy et al. 1973a), and with adverse prognosis for walking ability in claudicants (Dormandy et al. 1973b). Subsequently, the same group found that decreased blood filterability (its ability to flow in narrow vessels) was also present in patients with peripheral vascular disease, and correlated with clinical severity (Reid et al. 1976). Several other groups have since confirmed abnormal blood rheology in patients with arterial disease and its relationship to severity or outcome. This occurs not only in those with the most widespread disease and consequently the highest morbidity and mortality (peripheral vascular disease), but also in those presenting with coronary artery disease (Lowe et al. 1980a), stroke (Lowe et al. 1987a) or arterial “risk factors” (Lowe et al. 1987b). These findings have been summarised in recent reviews (Lowe 1986, 1987a, 1988, 1990a; Chien et al. 1987; Nash and Dormandy 1990).
A technique to measure cellular deformability is described, in which the cell suspension is subjected to well defined shear stresses, and the elongation of the cells is measured using diffractometry. With this technique, cellular deformability of a population of cells can be measured rapidly using small quantities of cells. The advantage of the present technique is that decreased deformability of the cells can be quantitated, and the presence of small populations of undeformable cells can be detected.
The capacity of red blood cells to deform is of crucial importance for both macro and microcirculation. A satisfying technique for the measurement of this parameter is lacking so far. We have developed and tested in various studies an instrument for automatic measurement of red cell deformability by laser diffractometry. Recently, it appeared that the applicability of the instrument could be extended for measuring another structural hemorheological parameter, red blood cell aggregation. In this communication, a description of the Laser-assisted Optical Rotational Cell Analyser (LORCA) is followed by the general methodology for the measurement of both red blood cell deform ability and aggregation, demonstrating the practical versatility ofthis instrument in the field of hemorheology.
The laser-diffraction technique has been applied to design a slit rheometer for measuring red blood cell deformability over a range of shear stress. Flow-rate and pressure-drop measurements are replaced with a measurement of pressure variation with time. Using a precision pressure transducer, one can measure the variation of pressure in the vacuum chamber, p(t), from which the shear stress and shear rate are mathematically calculated. In addition, a laser beam traverses a diluted blood suspension and is diffracted by red blood cells (RBCs) in the volume. The diffraction patterns are captured by a charge coupled device-video camera, linked to a frame grabber integrated with a computer. When deforming under decreasing shear stress, RBCs change gradually from the prolate ellipsoid towards a circular biconcave morphology. The elongation index as a measure of RBC deformability is determined from an isointensity curve in the diffraction pattern using an ellipse-fitting program. The advantages of this design are simplicity, i.e., ease of operation and no moving parts, low cost, short operating time, and the disposable kit which is in contact with the blood sample. © 2004 American Institute of Physics.
Experimental and theoretical work on the rheological properties of suspensions are reviewed. Attention is focused on systems consisting of rigid, neutrally buyoant particles suspended in Newtonian fluids; no restrictions, however, are placed on the concentration of the particles or on the forces acting in the suspension. The assumption that an effective viscosity depending solely on the volume fraction of the particles suffices to describe the rheology of suspensions is examined and shown to be inadequate. Indeed, the experimental evidence strongly supports the view that suspensions behave macroscopically as non‐Newtonian fluids whose rheological properties are influenced by a large number of factors; these factors are listed. The various theories that have been put forward to explain the flow of suspensions are discussed, with particular emphasis being placed on the nature of the approximations made, so that purely empirical formulas can be clearly separated from those having a theoretical basis. Suggestions for future work, both theoretical and experimental, are provided.