Decrease Of Erythrocyte Deformability Research Articles

Effect of the combined administration of metoprolol and dihydroquercetin on the rheological properties of blood in spontaneously hypertensive rats (SHRs)

Introduction. Hyperviscosity syndrome plays an important role in the pathogenesis of arterial hypertension and its complications associated with impaired microcirculation in target organs. Therefore, along with the use of antihypertensive drugs, it is important to pay attention to the correction of the hyperviscosity syndrome with means of hemorheological agents.The aimis to study the effect of metoprolol and its combined use with dihydroquercetin (DHQ) on the rheological parameters of blood in rats with spontaneous arterial hypertension.Materials and methods. The experiments were carried out on normotensive male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). SHRs of the experimental groups received metoprolol (50 mg/kg) or metoprolol and DHQ (50 mg/kg each) daily intragastrically for 6 weeks in 1 % starch mucus; SHRs of the control group and normotensive rats received 1 % starch mucus according to the same scheme. Systemic blood pressure was registered in awake animals. Blood was sampled from the catheterized right common carotid artery. Blood viscosity, plasma viscosity, hematocrit, erythrocyte aggregation and deformability were studied.Results. Compared with the parameters in normotensive rats, SHRs showed significant increase of blood viscosity, hematocrit, erythrocyte aggregation, and decrease of erythrocyte deformability. The course administration of metoprolol induced to a further increase in blood viscosity at low shear rates (15–45 s–1); plasma viscosity, hematocrit and micro-rheological parameters in rats of this group did not significantly differ from those in the control. With the combined administration of metoprolol and DHQ, blood viscosity at shear rates of 300 and 450 s–1and erythrocyte aggregation were significantly lower than in the control SHRs.Conclusions. The course administration of metoprolol increases the severity of the hyperviscosity syndrome in SHRs. The use of DHQ together with metoprolol partially eliminates adverse effects of the beta blocker on blood rheology parameters.

Hipertensión inducida por el Embarazo Nuevos Conceptos.

La hipertensión inducida por el embarazo es una enfermedad que complica el embarazo progresiva y solapadamente, acarreando con frecuencia graves consecuencias maternas y perinatales. Conocemos que es una alteración bioquímica y orgánica del endotelio vascular, con predominio de sustancias contráctiles sobre las relajantes, –lo que lo hace lábil a las sustancias vasopresoras–, así como incremento de la actividad mitogénica y anormalidades de los mecanismos de coagulación. Hay disminución del volumen plasmático en relación directa con la hipertensión, disminución de la deformabilidad del eritrocito, placentación defectuosa, todo lo cual sugiere un fondo inmunológico y genético, que empieza con el inicio del embarazo. No existen análisis premonitorios, salvo los que indican gravedad de la enfermedad. Es preferible considerar la presión diastólica =80mm de Hg como hipertensión. La madre puede colaborar en vigilar el crecimiento y movilidad de su bebé mientras está en el útero. La ecografía establece el desarrollo y el bienestar fetal. El sulfato de magnesio y la nifedipina, en nuestro medio, son las drogas de elección para tratar las crisis hipertensivas, recomendaciones no bajar la presión diastólica por debajo de 100 mm de Hg para evitar empeorar el flujo placentario. El tratamiento de la hipertensión inducida por el embarazo consiste en el nacimiento de feto y placenta, existiendo en el periodo posterior inmediato al parto riesgo de convulsiones y shock hipovolémico, así como de coagulación intravascular diseminada. La prolongación del embarazo puede dejar secuela hipertensiva materna pocos años más tarde y, en el feto, hipertensiva y secuelas neurológicas. El manejo de la enfermedad requiere atención especializada del ginecoobstetra, con amplio conocimiento de su fisiopatología y las modificaciones maternas y fetales. Se explica las razones por las que se hace necesaria una modificación de la clasificación de las enfermedades hipertensivas que complican el embarazo.

Increased calcium deposits and decreased Ca 2+-ATPase in erythrocytes of ascitic broiler chickens

The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca 2+ and Ca 2+-ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca 2+-ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca 2+-ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers.

Hemorheological Mechanisms in Alzheimer's Disease

The aim of the present study was to elucidate the underlying mechanisms responsible for hemorheological abnormalities in elderly patients with Alzheimer's disease (AD). Twenty-one patients with AD and twenty-three age-matched healthy controls (CON) were studied. We used a controlled-shear rate rheometer generating various flow fields in vitro for simulating blood flow in vivo. The applied experimental techniques provided valid and quantitative data for the analysis of hemorheological abnormalities associated with AD. Principal blood biochemical parameters and hemorheological parameters, including blood viscosity, erythrocyte deformability, erythrocyte aggregation and oxygen transport efficiency of blood were assessed. The results show no statistically significant difference in most of the blood biochemical parameters between the AD patients and the CON, except that fibrinogen concentration and mean corpuscular cell volume level of erythrocytes (MCV) were significantly higher in the AD patients. Hemorheological parameters including blood viscosity, plasma viscosity, and blood viscoelasticity in the AD patients were considerably higher than the respective factors in the CON. Owing to the MDA levels of the AD patients being significantly higher than that of the CON, the AD patients also showed a decrease in erythrocyte deformability and an increase in blood flow resistance despite the lack of any significant difference in erythrocyte rigidity. In addition, the erythrocyte aggregation of AD patients was higher than that of the CON and reduced oxygen transport efficiency of blood was observed in the AD patients. The hemorheological abnormalities found in AD patients may be explained by the parallel findings of oxidative damage on erythrocyte membranes that could result in a decrease of erythrocyte deformability. Furthermore, the oxidative stress-induced elevation of fibrinogen concentration could lead to accelerated erythrocyte aggregation as a consequence of a rise in blood viscosity and blood viscoelasticity. Taken together, these factors may impair the oxygen transport efficiency of blood in AD patients.

Effect of asymmetric dimethylarginine on atherogenesis and erythrocyte deformability in apolipoprotein E deficient mice

Previous investigations have shown that the level of asymmetric dimethylarginine (ADMA) was increased in hypercholesterolemic animal and humans, and the decreased erythrocyte deformability has been suggested to be a factor contributing to atherogenesis. In the present study, we investigated the effect of ADMA, endogenous or exogenous, on atherogenesis and erythrocyte deformability in apolipoprotein E deficient (ApoE−/−) mice. On a regular chow diet, ApoE−/− mice or C57BL/6 J mice at 12 weeks of age were treated with ADMA (5 mg/kg/day) for 4 weeks. Atherosclerotic lesion area, erythrocyte deformability, plasma lipids and asymmetric dimethylarginine (ADMA) level were determined. Plasma concentrations of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), ADMA, and atherosclerotic lesion area were significantly increased, and the level of plasma high-density lipoprotein-cholesterol (HDL-C), erythrocyte deformability in ApoE−/− mice were markedly decreased compared with that of C57BL/6J mice ( P < 0.05 or P < 0.01). Exogenous ADMA treatment increased the plasma TG level, produced atherosclerotic lesions, and decreased erythrocyte deformability in C57BL/6J mice ( P < 0.05 or P < 0.01). Treatment with exogenous ADMA further increased the plasma TG level and lesion areas, and decreased erythrocyte deformability in ApoE−/− mice. In vitro, exogenous ADMA caused a decrease of erythrocyte deformability in a concentration-dependent manner, and the effect of ADMA was reversed by L-arginine. The present results suggest that endogenous ADMA is an important contributor to the development of atherosclerosis and that reduction of erythrocyte deformability and impaired endothelial function induced by ADMA may be an important factor facilitating atherosclerotic lesions.

Effects of estrogen and androgen level on erythrocyte deformability in endocrinological erectile dysfunction

Objective: To evaluate the effect of estrogen and androgen levels on erythrocyte deformability in endocrinological erectile dysfunction patients. Methods: The estrogen level, androgen level, IR of 30 psychogenic and 15 endocriological ED were studied and the correlation between the estrogen and androgen levels and RI were analyzed. Results: There is a negative correlation between the androgen and estrogen levels and IR; The IR (5.9033 ± 1.9369), η10 (11.2810 ± 1.3120) values in the endcocrinological group were markedly higher than those (4.0589 ± 1.55339, 9.8321 ± 1.6415) in the psychogenic group. Conclusion: The lower level of the estrogen and androgen in endocrinological ED patients may result in the decrease of erythrocyte deformability causing the increase in blood viscosity. To enhance in time the levels of estrogen and androgen might improve penile erectile function of endocrinological ED patients in hemodynamics.

Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction.

Gamma-glutamyltranspeptidase (GGT) is a well known cell plasma membrane and serum circulating enzyme. In clinical chemistry, GGT is used as a marker of alcohol consumption and drug uptake. Serum GGT activity varies in hepatobiliary diseases and cancer. This enzyme is involved in glutathione (GSH) metabolism, which is generally associated with antioxidant properties. However, in recent years, findings from our group and from others showed that GGT-catalysed extracellular metabolism of GSH leads, in the presence of iron, to the generation of reactive oxygen species (ROS). It was demonstrated that those highly reactive species oxidise lipids, cell surface protein thiols or activate transcriptional factors such as Nuclear Factor kappaB (NFkappaB). The objective of the present work is to determine whether the red blood cells are targets for plasma GGT-initiated pro-oxidant reaction. The results obtained demonstrate that the GGT/GSH/iron system oxidises isolated erythrocyte membranes. A significant release of haemoglobin and a decrease of erythrocyte deformability are also observed. In addition, in vivo studies showed a relationship between plasma GGT activity and erythrocyte deformability in 20 studied subjects. In conclusion, GGT-mediated ROS production is able to oxidise erythrocytes and thus disturbs their functions.

Changes of Hemorheologic Properties during Normal Human Pregnancy

To investigate alterations of hemorheologic properties during pregnancy, we measured the hematocrit (Hct) and fibrinogen levels, blood viscosity, and erythrocyte deformability in 10 healthy nonpregnant women and in 10 women with uncomplicated pregnancies. The Hct decreased during pregnancy, while the plasma fibrinogen concentration was elevated. No significant changes in blood viscosity were observed throughout pregnancy. Erythrocyte deformability was significantly decreased in pregnancy when compared to the nonpregnant state, but returned to the nonpregnant level by the 7th postpartum day. These findings suggest that adequate microcirculation is maintained in the uteroplacental unit during gestation by hemodilution, which prevents an elevation of blood viscosity despite the increase in fibrinogen and the decrease of erythrocyte deformability. These changes are thus thought to be among the physiological maternal adaptations to fetal growth and development.

Abnormal rheological response of erythrocytes caused by nitroimidazoles and hyperthermia.

The aim of the present study was to investigate the response of erythrocytes to hyperthermia in combined treatment with nitroimidazoles. The efficiency of nitroimidazoles and physical agents on the rheological response of erythrocytes was measured by the viscosimetric-diffractometric method in a continuous osmotic gradient with constant shear stress of 100 dyn/cm2. We found that three newly synthesized dinitro- or nitroimidazole derivatives caused oxidative damage of erythrocytes in aerobic conditions. Nitroimidazole structure-dependent decrease of erythrocyte deformability was accompanied by oxidation of haemoglobin and depletion of reduced glutathione, lipid peroxidation and alteration of membrane structure indicated by a decrease of the ANS fluorescence intensity and increased production of MDA. Heat treatment per se (from 42 to 45 degrees C) only slightly decreased the erythrocyte deformability, but markedly enhanced the structure-dependent effect of nitroimidazoles. Erythrocytes heated at 45 degrees C with dinitroimidazole derivative III lost their deformability without haemolysis. Dithiothreitol used in combination with nitroimidazoles during a heating period to 43.5 degrees C protected cell deformability entirely, indicating an important role for disulphide bond formation in membrane proteins submitted to oxidative stress and hyperthermia.

Decrease of erythrocyte deformability in cyclosporine-treated renal transplant patients: correction with fish oil as well as corn oil

Twenty-nine renal transplant recipients with good, stable transplant function were included in a double-blind cross-over study to investigate the effects of different immunosuppressive treatment modalities and also the effects of fish oil and corn oil supplementation on erythrocyte deformability. Ten patients were treated with cyclosporine (CyA) only, 10 patients with CyA and prednisolone, and 9 patients with azathioprine and prednisolone. Erythrocyte deformability, as measured by an ektacytometric technique, was significantly decreased in both CyA-treated groups compared with the azathioprine-prednisolone-treated group, and this decrease was corrected with fish oil and with corn oil. The cause and the clinical significance of less deformable erythrocytes due to CyA are not yet clear. However, less deformable erythrocytes could play a role in the genesis of the complications of CyA.

Effects of two low osmolality contrast media on red blood cell filterability and aggregation in vitro

The in vitro effects of ionic ioxaglate and non-ionic iopamidol were compared. Filtration measurements were carried out on an hemorheometer; erythrocyte aggregation was evaluated by means of an erythrocyte aggregometer, and red blood cell morphology was observed with an optical microscope. Ioxaglate and iopamidol reduced erythrocyte filterability to the same extent; by contrast neither ionic nor non-ionic contrast media significantly modified aggregation or shape of red blood cells. The decrease of erythrocyte deformability observed in this study may cause clotting in catheters or syringes during angiographies investigations.

Parallel decrease of erythrocyte membrane deformability and spectrin solubility at low pH

Reduction of pH over the range 6.0–4.5 results in a decrease of erythrocyte deformability in parallel with the induced progressive sphericity of cells. At low deformation rates employed, increase of hemoglobin viscosity was not significant. A decrease of membrane elasticity was detected in cells when sphering, the major determinant of cellular deformability, was prevented at pH 5.0 by hyperosmotic medium. The pronounced change of deformability and the reduced elasticity occurred at calculated intracellular pH values at which solubility in vitro of extracted erythrocyte spectrin is also markedly reduced. The parallel decrease of deformability and spectrin solubility supports the hypothesis that spectrin aggregation may contribute to regulation of erythrocyte deformability through effects on shape and membrane elastic characteristics.

Parallel Decrease of Erythrocyte Membrane Deformability and Spectrin Solubility at Low pH

Reduction of pH over the range 6.0-4.5 results in a decrease of erythrocyte deformability in parallel with the induced progressive sphericity of cells. At low deformation rates employed, increase of hemoglobin viscosity was not significant. A decrease of membrane elasticity was detected in cells when sphering, the major determinant of cellular deformability, was prevented at pH 5.0 by hyperosmotic medium. The pronounced change of deformability and the reduced elasticity occurred at calculated intracellular pH values at which solubility in vitro of extracted erythrocyte spectrin is also markedly reduced. The parallel decrease of deformability and spectrin solubility supports the hypothesis that spectrin aggregation may contribute to regulation of erythrocyte deformability through effects on shape and membrane elastic characteristics.