Changes In Erythrocyte Deformability Research Articles

Seasonal changes in blood rheology in little ground squirrels.

The annual cycle of small ground squirrels (Spermophilus pygmaeus) consists of 2 periods: wakefulness (spring-autumn) and hibernation (winter). During the active period, ground squirrels breed (spring), accumulate fat reserves (summer) and prepare for hibernation (autumn). We suppose that the rheological properties of blood and the deformability of erythrocytes can change in different seasons of the animal's wakefulness period to adequately provide tissues with oxygen. The aim of this study was to identify possible adaptive changes in erythrocyte deformability and erythrocyte indices in ground squirrels during their active period. The deformability of erythrocytes was studied by ektacytometry in an osmotic gradient. It was found that in spring, after the arousal of ground squirrels, erythrocytes have the highest deformability (El_max), hydration (O_hyper), water permeability (El_min) and osmotic stability (∆O). In summer, compared with spring, the deformability of erythrocytes decreases, and the average volume of erythrocytes (MCV) also decreases. In autumn, before hibernation, the integral deformability of erythrocytes, their hydration, as well as the range of osmotic stability of erythrocytes increases relative to the summer period. In summer and autumn, in contrast to spring, the average concentration of hemoglobin in the erythrocyte (MCHC) increases. At low shear stress (1 Pa) in summer and autumn, osmoscan becomes a pronounced polymodal form, indicating a change in the viscoelastic properties of ground squirrel erythrocyte membranes. Thus, for the first time, we discovered seasonal variability in the deformability of ground squirrel erythrocytes, which is consistent with the spring-summer activity of animals and preparation for hibernation.

Effect of Hydrogen Sulfide on Deformability of Rat Erythrocytes.

The influence of a hydrogen sulfide donor NaHS (2×10-5-10-3 M) on the rat erythrocyte deformability was analyzed by laser diffractometry. NaHS (6×10-5 M) increased, while NaHS (10-3 M) reduced erythrocyte deformability. The effect of NaHS (6×10-5 M) was similar to that of NO donor sodium nitroprusside (SNP, 10-7 M). However, simultaneous use of NaHS (6×10-5 M) and SNP induced less pronounced changes in erythrocyte deformability than their individual application. It is likely H2S, similar to NO, is involved in the regulation of erythrocyte deformability in the microvascular bed.

Human erythrocytes: cytoskeleton and its origin.

In the last few years, erythrocytes have emerged as the main determinant of blood rheology. In mammals, these cells are devoid of nuclei and are, therefore, unable to divide. Consequently, all circulating erythrocytes come from erythropoiesis, a process in the bone marrow in which several modifications are induced in the expression of membrane and cytoskeletal proteins, and different vertical and horizontal interactions are established between them. Cytoskeleton components play an important role in this process, which explains why they and the interaction between them have been the focus of much recent research. Moreover, in mature erythrocytes, the cytoskeleton integrity is also essential, because the cytoskeleton confers remarkable deformability and stability on the erythrocytes, thus enabling them to undergo deformation in microcirculation. Defects in the cytoskeleton produce changes in erythrocyte deformability and stability, affecting cell viability and rheological properties. Such abnormalities are seen in different pathologies of special interest, such as different types of anemia, hypertension, and diabetes, among others. This review highlights the main findings in mammalian erythrocytes and their progenitors regarding the presence, conformation and function of the three main components of the cytoskeleton: actin, intermediate filaments, and tubulin.

Effect of Cerium on Erythrocyte Mechanical Properties

Lanthanide’s are known as rare earth elements and are used in many areas. Although the place of Cerium in the Lanthanide family in its biological importance in mammalian physiology is not fully known, a human weighing 70 kg contains about 40 mg Cerium. Soluble Ce3+ salts (nitrate, acetate, chloride, etc.) are used for many biomedical purposes and in particular act as calcium analogues in biological systems. In non-physiological flow conditions occurring in extracorporeal circulation areas, increased calcium ions within the cell play a role in reducing erythrocyte deformability. In this study, it is aimed to show the possible effects of Cerium on changes in erythrocyte deformability in shear stress at sub-hemolytic level. For this purpose, blood samples were taken from adult male volunteers. Normal erythrocyte deformability was measured at nine shear rates between 0.5 and 50 Pa, followed by stress application at a slip rate of 290 Pa for 300 seconds without removing the sample from the system, followed by erythrocyte deformability at shear rates of 0.5-50 Pa. There was no significant difference between the erythrocyte deformability values of the control and Cerium incubated blood samples before stress application. However, significant differences were found after stress application (p <0.01). Incubation of erythrocytes with Cerium did not cause any change in erythrocyte deformability, but caused further deterioration of erythrocytes after mechanical stress. Cerium chloride, which we use in our study, should be kept in mind that under normal conditions, even if there is no negative effect on erythrocyte mechanics, conditions change, erythrocytes are exposed to short-term sub-hemolytic mechanical effects and their mechanical properties are deteriorated. Keywords: Lanthanide, Cerium, Erythrocyte, Deformability, Mechanical Stress DOI: 10.7176/JSTR/5-8-11

Changes in erythrocyte deformability during day and possible role of melatonin

The deformability of erythrocytes is their ability to change shape in order to pass through the capillaries. Th is is necessary for quality of microcirculation and sufficient delivery of oxygen to the tissues. Th e aim of our study was to investigate the possible spontaneous changes in the erythrocyte deformability during day and evaluation of the possible direct effects of melatonin (hormone involved in regulation of biorhythms) on the erythrocyte deformability. Samples of capillary blood were taken from 12 healthy volunteers in the morning (8:00) and early in the evening (16:30). Determination of erythrocyte deformability was done based on the measurement of their filtrability. It was measured immediately aft er the sample collection and 2-hour lasting incubation without or with melatonin (2000 μmol/L). Erythrocyte deformability was significantly lower in the morning (filtrability index: 0.68±0.01 morning vs. 0.71±0.01 early evening, p<0.05). Th e incubation of blood samples with melatonin did not have impact on deformability. We suggest the presence of diurnal changes in erythrocyte deformability with worse values in the morning that may contribute to higher risk of ischemic attacks in the morning hours. Direct in vitro effect of melatonin on deformability was not observed, but possible in vivo effects cannot be excluded.

Changes in erythrocyte deformability during experimental hyperthyroidism

Changes in erythrocyte deformability during experimental hyperthyroidism

A Plasmodium falciparum S33 proline aminopeptidase is associated with changes in erythrocyte deformability

Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies.

Effects of detyrosinated tubulin on Na+,K+-ATPase activity and erythrocyte function in hypertensive subjects

Formation of tubulin/Na+,K+-ATPase (NKA) complex in erythrocytes of hypertensive subjects results in a 50% reduction in NKA activity. We demonstrate here that detyrosinated tubulin, which is increased in hypertensive erythrocytes membranes, enhances the inhibitory effect of acetylated tubulin on NKA activity. Moreover, we report a reduced content and activity of the enzyme tubulin tyrosine ligase in erythrocytes of hypertensive subjects. Such alterations are related to changes in erythrocyte deformability. Our findings indicate that the detyrosination/tyrosination cycle of tubulin is important in regulation of NKA activity, and that abnormalities in this cycle are involved in hypertension development.

Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin.

ATP release from erythrocytes in response to reduced oxygen (O2) tension stimulates local vasodilation, enabling these cells to direct perfusion to areas in skeletal muscle in need of O2. Erythrocytes of humans with type 2 diabetes do not release ATP in response to low O2. Both C-peptide and insulin individually inhibit low O2-induced ATP release from healthy human erythrocytes, yet when coadministered at physiological concentrations and ratios, no inhibition is seen. Here, we determined: that 1) erythrocytes of healthy humans and humans with type 2 diabetes possess a C-peptide receptor (GPR146), 2) the combination of C-peptide and insulin at physiological ratios rescues low O2-induced ATP release from erythrocytes of humans with type 2 diabetes, 3) residual C-peptide levels reported in humans with type 2 diabetes are not adequate to rescue low O2-induced ATP release in the presence of 1 nM insulin, and 4) the effects of C-peptide and insulin are neither altered by increased glucose levels nor explained by changes in erythrocyte deformability. These results suggest that the addition of C-peptide to the treatment regimen for type 2 diabetes could have beneficial effects on tissue oxygenation, which would help to ameliorate the concomitant peripheral vascular disease.

Erythrocyte deformability dependence on band 3 protein in an in-vitro model of hyperfibrinogenemia

Recent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the erythrocyte deformability was determined. The present study shows that in the presence of higher fibrinogen concentrations, similar to those found in inflammatory conditions, erythrocyte deformability is increased only when band 3 is dephosphorylated by the presence of syk inhibitor and at low shear stress. On the contrary, no changes were verified in the presence of fibrinogen when band 3 is allowed to be phosphorylated by inhibiting the phosphotyrosine phosphatase enzyme activity with calpeptin. We also observed that the presence of fibrinogen at higher concentration does not induce changes in erythrocyte deformability in the absence of modulators of the band 3 phosphorylation degree. However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study.

Changes of local and systemic hemorheological properties in intestinal ischemia‐reperfusion injury in the rat model

The aim of this study was to investigate intestinal ischemia-reperfusion and its local and systemic hemorheological relations in the rat. Ten anaesthetized female CD outbred rats were equally divided into 2 experimental groups. (1) Ischemia-reperfusion (I/R): the superior mesenterial artery was clipped for 30 minutes. After removing the clip, 60 minutes of the reperfusion was observed before extermination. Blood samples were taken from the caudal caval vein and from the portal vein before ischemia, 1 minute before and after clip removal, and at the 15th, 30th, and 60th minutes of the reperfusion. (2) Sham operation: median laparotomy and blood sampling were done according to the timing as in I/R group. Hematological parameters, red blood cell aggregation, and deformability were determined. Leukocyte count and mean volume of erythrocytes increased slightly but continuously in portal venous samples during the reperfusion period. Red blood cell aggregation values were higher in portal blood by the end of ischemia, and then became elevated further comparing to the caval venous blood. Both in caval and portal venous samples of I/R group red blood cell deformability significantly worsened during the experimental period compared to its base and Sham group. In portal blood red blood cell deformability was impaired more than in caval vein samples. Histology showed denuded villi, dilated capillaries, and the inflammatory cells were increased after a 30 minutes ischemia. In conclusion, intestinal ischemia-reperfusion causes changes in erythrocyte deformability and aggregation, showing local versus systemic differences in venous blood during the first hour of reperfusion.

Changes In Erythrocyte Deformability In Alzheimer's Disease: A Role For Nitric Oxide Synthase

Changes In Erythrocyte Deformability In Alzheimer's Disease: A Role For Nitric Oxide Synthase

Improved haemorrheological properties by Ginkgo biloba extract (Egb 761) in type 2 diabetes mellitus complicated with retinopathy

Background & Aims: Abnormal haemorrheological property changes in erythrocyte deformability, plasma and blood viscosity, and blood viscoelasticity may play very important roles in the development of microangiopathies in diabetes mellitus (DM). In this study, we demonstrate the improvement in abnormal haemorrheological parameters in DM with ingestion of Ginkgo biloba extract 761 (Egb 761). Methods: Haemorrheological parameters before and 3 months after Egb 761 oral ingestion were determined in 25 type 2 DM patients with retinopathy. These parameters included lipid peroxidation stress of erythrocytes, erythrocyte deformability, plasma and blood viscosity, blood viscoelasticity, and retinal capillary blood flow velocity. Results: After taking Egb 761 orally for 3 months, the blood viscosity was significantly reduced at different shear rates, by 0.44±0.10 ( γ=400), 0.52±0.09 ( γ=150) and 2.88±0.57 ( γ=5). Viscoelasticity was significantly reduced in diabetic patients by 3.08±0.78 (0.1 Hz). The level of erythrocyte malondialdehyde (MDA) was reduced by 30%; however, the deformability of erythrocyte was increased by 20%. And lastly, retinal capillary blood flow rate was increased from 3.23±0.12 to 3.67±0.24 cm min −1. Conclusion: In this preliminary clinical study, 3 months of oral administration of Egb 761 significantly reduced MDA levels of erythrocytes membranes, decreased fibrinogen levels, promoted erythrocytes deformability, and improved blood viscosity and viscoelasticity, which may facilitate blood perfusion. Furthermore, it effectively improved retinal capillary blood flow rate in type 2 diabetic patients with retinopathy.

Changes in erythrocyte deformability after liver resection for hepatocellular carcinoma associated with chronic liver disease.

Erythrocyte deformability is an important factor in the microcirculation. The deformability in patients with chronic liver disease is less than normal. We studied changes in erythrocyte deformability in 32 patients undergoing liver resection for hepatocellular carcinoma with underlying chronic liver disease to investigate whether the measurement of deformability gives information useful for postoperative management. We measured erythrocyte deformability as erythrocyte transit time (ETT) before and after resection, as well as the erythrocyte adenosine triphosphate level, mean corpuscular volume, mean corpuscular hemoglobin concentration, and indices of liver function. The 15-minute indocyanine green retention rate (ICGR15) was measured before resection. Correlations between the change in deformability and these values were evaluated, as was correlation with the scale of the operation and with the occurrence of postoperative complications. Mean ETT was higher in the patients before resection than in healthy volunteers. ETT was correlated with serum high density lipoprotein-cholesterol (p < 0.05). The incidence of postoperative complications was higher (p = 0.001) in the patients (group A) with ETT increased during the first 3 postoperative days by >/=1 SD of the mean of the preoperative value than in patients (group B) with less change. Of the 12 patients whose ICGR15 value was >/=20%, all 9 patients in group A had postoperative complications. The increase in ETT (decrease in erythrocyte deformability) is associated with the development of postoperative complications. The measurement of erythrocyte deformability gives information useful for postoperative management, and special monitoring for postoperative complications is necessary in patients with the increase soon after liver resection.

Effects of sodium and potassium concentrations and pH on equine erythrocyte volume and deformability

During strenuous exercise, equine erythrocyte deformability is transiently decreased. Decreased deformability is associated with increased cell volume, decreased cell density and increased intracellular sodium, potassium and chloride concentrations. To better understand these changes, we attempted to reproduce exercise-associated changes in erythrocytes in vitro by adjusting plasma sodium, potassium and pH to levels which occur during racing activity. Increasing plasma sodium to 145 meq/1 and plasma potassium to 8 meq/1 resulted in decreased erythrocyte filterability, increased cell volume, and increased intracellular sodium, potassium and chloride. Incubation of erythrocytes with frusemide and bumetanide, but not ouabain or [(dihydroindenyl)oxy]alkanoic acid (DIOA), attenuated these changes. Decreasing plasma pH to 7.0 also decreased erythrocyte filterability, increased cell volume, and increased intracellular concentrations of sodium, potassium and chloride. Ouabain, but not frusemide or bumetanide, prevented the decrease infilterability and attenuated the increase in intracellular sodium. Addition of DIOA exacerbated the effect of pH on erythrocyte filterability. Therefore, exercise-associated changes in erythrocyte deformability, size and electrolyte concentration can be reproduced in vitro by increasing plasma sodium and potassium concentrations and by decreasing pH.

Changes in erythrocyte deformability in normal pregnancy and pregnancy-induced hypertension, as revealed by electron spin resonance.

To study changes in hemorheologic properties during pregnancy, erythrocyte deformability was measured by an electron spin resonance (ESR) method. The results obtained by this method showed that erythrocyte deformability in normal pregnancy decreased significantly in the first trimester compared with nonpregnant controls, and continued to decrease slightly as pregnancy progressed. On the other hand, erythrocyte deformability in severe pregnancy-induced hypertension (PIH) was significantly lower than that in the third trimester of normal pregnancy. Additionally, we found that the hematocrit level needed for erythrocytes to exhibit high deformability is lower during pregnancy. These results suggest that hemodilution in normal pregnancy, so-called hydremia, compensates for the decrease in erythrocyte deformability. Conversely, since erythrocytes become less deformable in a hemoconcentration condition in severe PIH, microcirculatory disturbance of various organs, including the uteroplacental unit, may occur. The lowered erythrocyte deformability may be one of the important pathologic features in PIH.

Blood viscosity measurements are not sensitive enough to detect changes in erythrocyte deformability in cyclosporin-treated patients and its subsequent reversal with fish and corn oil

ABSTRACf Rheological factors might be involved in the adverse effects of cyclosporin therapy. The use of cyclosporin is associated with a lower erythrocyte deformability. In order to investigate whether a decreased erythrocyte deformability was accompanied by changes in whole blood viscosity, measurements were done in patients in which a lower erythrocyte dcformability was found. Twenty nine stable renal transplant recipients, ten receiving cyclosporin, ten cyclosporin-prednisolone and nine azathioprin-prednisolone were supplemented in a double blind cross-over study with fish oil and corn oil for a period of four months each. No difference was found in whole blood viscosity between the patient groups with different immunosuppressive regimens, which means whole blood viscosity measurements did not detect decreased erythrocyte deformability. No decrease in whole blood viscosity was found in renal transplant recipients after supplementation of fish oil and com oil, while erythrocyte deformability increased in the cyclosporin-treated patients. Neither were plasma viscosity and the fibrinogen level influenced by fish or com oil. Whole blood and plasma viscosity are not influenced by the use of cyclosporin. It is concluded that whole blood viscosity measurements are not sufficient to detect changes in erythrocyte deformability and therefore separate measurements of erythrocyte deformability are indicated.

Changes in erythrocyte deformability in NaCl-induced right-sided cardiac failure in broiler chickens

Summary In this study, we tested the hypothesis that erythrocyte deformability is decreased in the development of cardiac failure induced by NaCl toxicosis. Deformability of erythrocytes and routine hematologic and biochemical variables were measured in 6 of 50 chickens that were given 5 g of NaCl/L in their drinking water from day 7 to day 42, and were compared with values in 6 of 50 healthy chickens given free access to tap water. Deformability was assessed by passing a 10% suspension of erythrocytes through a polycarbonate membrane with 5-µm pores. Chickens were euthanatized and heart and body weights were determined. Treatment with NaCl induced right-sided cardiac failure up to day 28. The ratios of heart weight to body weight were greater, for right ventricle by 20 to 64% and for left ventricle by 15 to 27%, attributable to NaCl treatment. Deformability of erythrocytes of NaCl-treated chickens was markedly decreased, in association with increased erythrocyte size and plasma Na+ concentration. However, only part of the decreased deformability could be explained by swelling of erythrocytes. Decreased deformability could not be explained by increased cell viscosity because mean corpuscular hemoglobin concentration, the primary determinant of erythrocyte viscosity, was decreased. Because decreased deformability of erythrocytes has been demonstrated previously to be associated with increased vascular resistance, decreased deformability may have contributed to the development of right-sided cardiac failure in these chickens.

Role of erythrocyte deformability in the acute hypoxic pressor response in the pulmonary vasculature

To assess the importance of erythrocyte deformability in the pulmonary hypoxic pressor response (HPR) we examined whether alterations is erythrocyte deformability are related to the differences between the brisk HPR in rats vs the small HPR in hamsters, and between the HPR in low altitude rats vs high altitude rats (10 days in 10% oxygen). Deformability of the erythrocytes (RBC) was assessed by filtering equal volume of RBC suspension through Nucleopore filters (4.7 μm) using the same pressure head across the filter. The results show that during hypoxia, rat RBC become relatively nondeformable compared to hamster's RBC. This finding is consistent with a large HPR in rats but a small HPR in hamsters. Furthermore, the deformability of RBC from high altitude rats became unaffected by hypoxia and was associated with blunting in the HPR in isolated lungs from high altitude rats. The HPR in isolated lungs from low altitude rats was larger when they were perfused with blood from normal rats (= 86% increase in resistance) than when perfused with blood from high altitude rats (= 36% increase in resistance). This finding further supports the possible role of RBC deformability in HPR. Inconsistent with the importance of deformability, however, was the finding that high altitude rat lungs had a blunted HPR whether they were perfused with normal rat blood or high altitude rat blood. This may be due to restructuring of the pulmonary microvascular bed in the lung from high altitude rats. The results favor the idea that changes in erythrocyte deformability may be responsible for the difference between the HPR in low altitude rats and hamsters, and between the HPR in low and high altitude rats. We suggest that ‘obstruction’ of the capillaries by less deformable erythrocyte is another factor, besides smooth muscle contraction, responsible for the hypoxic pressor response in the pulmonary vasculature.

Erythrocyte deformability changes in headache patients under flunarizine treatment.

Changes in erythrocyte deformability (ED) parameters have been investigated in 36 patients suffering from different forms of headache (classic and common migraine; migraine with interval headache; chronic tension headache) and treated with flunarizine (10 mg/day at bedtime). Patients were carefully selected in order to avoid any possible interference with the parameters under study, and smoke and drug use in particular (symptomatics included) were considered as criteria for exclusion from the trial. Controls of ED parameters were planned before treatment and after 20 and 35 days. Baseline ED alterations were present only among patients with chronic tension headache, but flunarizine treatment was able to positively modify ED parameters in these patients, as well as in migraine cases that showed normal baseline ED values. No correlation was found between patients' characteristics and baseline ED values, nor between ED changes under treatment and therapeutic effects of flunarizine.