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Clinical Hemorheology and... 2018In sickle cell disease (SCD), polymerization of hemoglobin S (HbS) leads to the formation of rigid, non-deformable sickled RBCs. Loss of RBC deformability, sickling and...
BACKGROUND
In sickle cell disease (SCD), polymerization of hemoglobin S (HbS) leads to the formation of rigid, non-deformable sickled RBCs. Loss of RBC deformability, sickling and irreversible membrane damage causes abnormal blood rheology, and increases viscosity which contributes to vasoocclusion and other SCD pathophysiology. GBT440 (generic name voxelotor) is a novel anti-polymerization and anti-sickling agent currently undergoing clinical evaluation for the treatment of SCD.
OBJECTIVE
The purpose of this study was to determine the effects of GBT440 on deformability of sickle RBCs (SS RBCs) and the hyperviscosity of sickle cell blood (SS blood).
METHODS
The mechanical and rheological properties of GBT440-treated SS RBCs were measured using micropipette and filtration techniques. The viscosity of sickle blood was measured using a Wells-Brookfield cone/plate viscometer.
RESULTS
GBT440 restored movement of deoxygenated SS RBCs through a gel filtration column and reduced the pressure required to pass SS RBCs through a polycarbonate filter. Moreover, GBT440 decreased the membrane shear elastic modulus of SS RBCs assessed via micropipette aspiration and reduced the hyperviscosity of SS blood under deoxygenated conditions.
CONCLUSIONS
GBT440 maintains SS RBC deformability and improves SS blood viscosity by inhibiting HbS polymerization under deoxygenated conditions. These results further support development of GBT440 as a disease-modifying agent in SCD patients.
Topics: Anemia, Sickle Cell; Blood Viscosity; Erythrocyte Deformability; Erythrocytes, Abnormal; Humans
PubMed: 29660913
DOI: 10.3233/CH-170340 -
Scientific Reports Apr 2016Platelet functions, including adhesion, activation, and aggregation have an influence on thrombosis and the progression of atherosclerosis. In the present study, a new...
Platelet functions, including adhesion, activation, and aggregation have an influence on thrombosis and the progression of atherosclerosis. In the present study, a new microfluidic-based method is proposed to estimate platelet adhesion and blood viscosity simultaneously. Blood sample flows into an H-shaped microfluidic device with a peristaltic pump. Since platelet aggregation may be initiated by the compression of rotors inside the peristaltic pump, platelet aggregates may adhere to the H-shaped channel. Through correlation mapping, which visualizes decorrelation of the streaming blood flow, the area of adhered platelets (APlatelet) can be estimated without labeling platelets. The platelet function is estimated by determining the representative index IA·T based on APlatelet and contact time. Blood viscosity is measured by monitoring the flow conditions in the one side channel of the H-shaped device. Based on the relation between interfacial width (W) and pressure ratio of sample flows to the reference, blood sample viscosity (μ) can be estimated by measuring W. Biophysical parameters (IA·T, μ) are compared for normal and diabetic rats using an ex vivo extracorporeal model. This microfluidic-based method can be used for evaluating variations in the platelet adhesion and blood viscosity of animal models with cardiovascular diseases under ex vivo conditions.
Topics: Animals; Blood Platelets; Blood Viscosity; Microfluidics; Platelet Activation; Platelet Aggregation; Rats
PubMed: 27118101
DOI: 10.1038/srep24994 -
PloS One 2018Red blood cells (RBCs) are the most abundant cells in human blood. Remarkably RBCs deform and bridge together to form aggregates under very low shear rates. The theory...
Red blood cells (RBCs) are the most abundant cells in human blood. Remarkably RBCs deform and bridge together to form aggregates under very low shear rates. The theory and mechanics behind aggregation are, however, not yet completely understood. The main objective of this work is to quantify and characterize RBC aggregates in order to enhance the current understanding of the non-Newtonian behaviour of blood in microcirculation. Suspensions of human blood were flowed and observed in vitro in poly-di-methyl-siloxane (PDMS) microchannels to characterize RBC aggregates. These microchannels were fabricated using standard photolithography methods. Experiments were performed using a micro particle image velocimetry (μPIV) system for shear rate measurements, coupled with a high-speed camera for flow visualization. RBC aggregate sizes were quantified in controlled and measurable shear rate environments for 5, 10 and 15% hematocrit. Aggregate sizes were determined using image processing techniques, while apparent viscosity was measured using optical viscometry. For the samples suspended at 5% H, aggregate size was not strongly correlated with shear rate. For the 10% H suspensions, in contrast, lowering the shear rate below 10 s-1 resulted in a significant increase of RBC aggregate sizes. The viscosity was found to increase with decreasing shear rate and increasing hematocrit, exemplifying the established non-Newtonian shear-thinning behaviour of blood. Increase in aggregation size did not translate into a linear increase of the blood viscosity. Temperature was shown to affect blood viscosity as expected, however, no correlation for aggregate size with temperature was observed. Non-Newtonian parameters associated with power law and Carreau models were determined by fitting the experimental data and can be used towards the simple modeling of blood's non-Newtonian behaviour in microcirculation. This work establishes a relationship between RBC aggregate sizes and corresponding shear rates and one between RBC aggregate sizes and apparent blood viscosity at body and room temperatures, in a microfluidic environment for low hematocrit. Effects of hematocrit, shear rate, viscosity and temperature on RBC aggregate sizes have been quantified.
Topics: Blood Viscosity; Erythrocyte Aggregation; Erythrocytes; Hematocrit; Humans; Microcirculation; Microfluidics
PubMed: 30024907
DOI: 10.1371/journal.pone.0199911 -
Biophysical Journal Jun 2021We have characterized the imbibed horizontal flow of sickle blood into 100-μm-diameter glass capillaries. We find that blood containing sickled cells typically...
We have characterized the imbibed horizontal flow of sickle blood into 100-μm-diameter glass capillaries. We find that blood containing sickled cells typically traverses the capillaries between three and four times as slowly as oxygenated cells from the same patient for all genotypes tested, including SS, AS, SC and Sβ thalassemia blood. Blood from SS patients treated with hydroxyurea has a viscosity intermediate between the SS and AA values. Blood containing cells that are not rigidified, such as normal red cells or oxygenated sickle cells, follows a simple Lucas-Washburn flow throughout the length of the 3-cm capillary. By fitting the flexible-cell data to the Lucas-Washburn model, a viscosity can be derived that is in good agreement with previous measurements over a range of volume fractions and is obtained using an apparatus that is far more complex. Deoxygenation sickles and thus rigidifies the cells, and their flow begins as Lucas-Washburn, albeit with higher viscosity than flexible cells. However, the flow further slows as a dense mass of cells forms behind the meniscus and increases in length as flow progresses. By assuming that the dense mass of cells exerts a frictional force proportional to its length, we derive an equation that is formally equivalent to vertical imbibition, even though the flow is horizontal, and this equation reproduces the observed behavior well. We present a simple theory using activity coefficients that accounts for this viscosity and its variation without adjustable parameters. In the course of control experiments, we have found that deoxygenation increases the flexibility of normal human red cells, an observation only recently published for mouse cells and previously unreported for human erythrocytes. Together, these studies form the foundation for an inexpensive and rapid point-of-care device to diagnose sickle cell disease or to determine blood viscosity in resource-challenged settings.
Topics: Anemia, Sickle Cell; Animals; Blood Viscosity; Capillaries; Erythrocytes; Erythrocytes, Abnormal; Humans; Mice; Oxygen
PubMed: 33861996
DOI: 10.1016/j.bpj.2021.03.040 -
Scientific Reports Nov 2018Sickle cell disease (SCD) is an inherited blood disorder associated with severe anemia, vessel occlusion, poor oxygen transport and organ failure. The presence of stiff...
Sickle cell disease (SCD) is an inherited blood disorder associated with severe anemia, vessel occlusion, poor oxygen transport and organ failure. The presence of stiff and often sickle-shaped red blood cells is the hallmark of SCD and is believed to contribute to impaired blood rheology and organ damage. Most existing measurement techniques of blood and red blood cell physical properties require sample contact and/or large sample volume, which is problematic for pediatric patients. Acoustic levitation allows rheological measurements in a single drop of blood, simultaneously eliminating the need for both contact containment and manipulation of samples. The technique shows that the shape oscillation of blood drops is able to assess blood viscosity in normal and SCD blood and demonstrates an abnormally increased viscosity in SCD when compared with normal controls. Furthermore, the technique is sensitive enough to detect viscosity changes induced by hydroxyurea treatment, and their dependence on the total fetal hemoglobin content of the sample. Thus this technique may hold promise as a monitoring tool for assessing changes in blood rheology in sickle cell and other hematological diseases.
Topics: Anemia, Sickle Cell; Blood Viscosity; Erythrocytes, Abnormal; Fetal Hemoglobin; Humans; Hydroxyurea; Rheology; Sound
PubMed: 30429489
DOI: 10.1038/s41598-018-34600-7 -
Scientific Reports May 2018Open heart surgeries are common for treating ischemic and heart valve disease. During cardiac surgery, cardiopulmonary bypass (CPB) can temporarily take over the...
Open heart surgeries are common for treating ischemic and heart valve disease. During cardiac surgery, cardiopulmonary bypass (CPB) can temporarily take over the function of heart and lungs. However, elevated red blood cell (RBC) aggregation may lead to the common side-effects such as microinfarction. We investigated blood physical properties changes and the correlation between blood microstructure, viscoelastic response and biochemical changes following surgery with CPB. We examined shear-rate dependent blood viscosity, elasticity and RBC aggregate size in the pre-surgery disease state, post-surgery state and long-term recovery state of cardiac surgical patients. Within a week following surgery, the patient hematocrit was significantly lower due to CPB. Despite lower RBC concentration, the RBC aggregate shape became larger and more rounded, which is correlated to the elevated plasma fibrinogen related to systemic inflammatory response. During the same period, the hematocrit-adjusted low shear rate viscosity increased significantly, as did the yield stress, indicating more solid-like behavior for blood. Six months to one year later, all the physical and biochemical properties measured returned to baseline.
Topics: Adult; Aged; Blood Viscosity; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Erythrocyte Aggregation; Erythrocytes; Female; Fibrinogen; Heart; Humans; Lung; Male; Middle Aged
PubMed: 29740114
DOI: 10.1038/s41598-018-25317-8 -
Clinical and Applied... May 2016Hemorheology, a measure of rheological properties of blood, is often correlated with cerebral blood flow and cardiac output; an increased blood viscosity may increase... (Randomized Controlled Trial)
Randomized Controlled Trial
Hemorheology, a measure of rheological properties of blood, is often correlated with cerebral blood flow and cardiac output; an increased blood viscosity may increase the risk of thrombosis or thromboembolic events. Previous studies have reported a large variation in hemorheological properties of blood among smokers. This prompted us to conduct coagulation experiments to evaluate the effect of cigarette smoking on hematological parameters, like cell counts, and coagulation parameters among young males in Al-Jouf region, Saudi Arabia. The hematological and coagulation parameters were used to relate the changes in viscosity and coagulation to smoking. A total of 321 male participants (126 nonsmokers and 195 smokers) were enrolled into the study as randomized sample. Complete blood count was measured by hematology analyzer, and coagulation tests were performed by coagulation analyzer. Thettest analysis was performed to compare the relationships of variables between the 2 groups. The results confirmed that smoking alters some hematology parameters leading to significant deterioration in blood flow properties. Smoking also increased the hematocrit (HCT), whole blood viscosity (WBV), and plasma viscosity (PV) but decreased the international normalized ratio (INR). The decrease in INR was found to be associated with the increase in WBV, PV, and HCT. Further investigations are necessary to assess the reversibility of such changes in cessation of smoking or other elements of influence.
Topics: Adult; Blood Coagulation; Blood Viscosity; Humans; Male; Saudi Arabia; Smoking
PubMed: 25505013
DOI: 10.1177/1076029614561319 -
Neurological Sciences : Official... Apr 2022Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an...
Whole blood viscosity (WBV) is the intrinsic resistance to flow developed due to the frictional force between adjacent layers of flowing blood. Elevated WBV is an independent risk factor for stroke. Poor microcirculation due to elevated WBV can prevent adequate perfusion of the brain and might act as an important secondary factor for hypoperfusion in acute ischaemic stroke. In the present study, we examined the association of WBV with basal cerebral perfusion assessed by CT perfusion in acute ischaemic stroke. Confirmed acute ischemic stroke patients (n = 82) presenting in hours were recruited from the single centre. Patients underwent baseline multimodal CT (non-contrast CT, CT angiography and CT perfusion). Where clinically warranted, patients also underwent follow-up DWI. WBV was measured in duplicate within 2 h after sampling from 5-mL EDTA blood sample. WBV was significantly correlated with CT perfusion parameters such as perfusion lesion volume, ischemic core volume and mismatch ratio; DWI volume and baseline NIHSS. In a multivariate linear regression model, WBV significantly predicted acute perfusion lesion volume, core volume and mismatch ratio after adjusting for the effect of occlusion site and collateral status. Association of WBV with hypoperfusion (increased perfusion lesion volume, ischaemic core volume and mismatch ratio) suggest the role of erythrocyte rheology in cerebral haemodynamic of acute ischemic stroke. The present findings open new possibilities for therapeutic strategies targeting erythrocyte rheology to improve cerebral microcirculation in stroke.
Topics: Blood Viscosity; Brain Ischemia; Cerebrovascular Circulation; Humans; Ischemic Stroke; Perfusion; Stroke
PubMed: 34669084
DOI: 10.1007/s10072-021-05666-5 -
Cardiovascular Diabetology Apr 2018Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear... (Comparative Study)
Comparative Study
BACKGROUND
Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function.
OBJECTIVE
We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness.
METHODS
The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software.
RESULTS
Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS).
CONCLUSIONS
This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.
Topics: Aged; Benzhydryl Compounds; Blood Viscosity; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Incretins; Liraglutide; Male; Middle Aged; Prospective Studies; Regional Blood Flow; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Stress, Mechanical; Time Factors; Treatment Outcome
PubMed: 29631585
DOI: 10.1186/s12933-018-0695-y -
American Journal of Physiology. Heart... Oct 2000We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during...
We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml. 100 g(-1). min(-1), respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98 to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1). min(-1) and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.
Topics: Anemia; Animals; Blood Flow Velocity; Blood Viscosity; Cerebrovascular Circulation; Hemodilution; Hypercapnia; Hypoxia; Male; Rats; Rats, Sprague-Dawley; Reference Values
PubMed: 11009484
DOI: 10.1152/ajpheart.2000.279.4.H1949