Intermittent hypoxia training does not change erythrocyte aggregation indicators in young, healthy men.

Background: The increasing popularity of hypoxic training as a training method to improve physical performance indicates the need to study the effects of this type of intervention on blood morphological and rheological indices, since the adaptive changes that follow such training mainly affect blood indices. In this study, the effects of a 4 weeks of intermittent hypoxic training on blood morphological and rheological indicators in physically active men were assessed. Methods: Forty-eight young, physically active men, participated in the study. Participants were randomly divided into three groups: two training groups and a control group without intervention (CTRL). Each group consisted of 16 participants. Training groups performed interval training (three times per week, 4 weeks, 12 workouts) under different conditions: in hypoxia (IHT; fraction of inspired oxygen (FiO2) = 14.4%) or in normoxia (NT; FiO2 = 20.9%). The control group performed only two workouts 4 weeks apart. Blood was taken during the first and last training session at rest, and 3 minutes after training. Results: After the last training session, there was a significant increase in mean corpuscular volume and a decrease in mean corpuscular haemoglobin concentration measured at rest only in the IHT group. There was also a significant decrease in resting aggregation amplitude for the IHT and CTRL groups. There was no difference in change of post-exercise plasma volume between first and last training session. Conclusion: The applied intermittent interval training in conditions of normoxia and hypoxia had no significant impact on resting aggregation parameters. This suggest that training under hypoxic conditions does not cause adverse rheological changes.

Hormonal Control of Blood Viscosity.

The hemodynamic milieu differs throughout the vascular tree because of varying vascular geometry and blood velocities. Accordingly, the risk of turbulence, which is dictated by the Reynolds and Dean numbers, also varies. Relatively high blood viscosity is needed to prevent turbulence in the left ventricle and aorta, where high-velocity blood changes direction several times. Low blood viscosity is needed in the capillaries, where erythrocytes pass through vessels with a diameter smaller than their own. In addition, higher blood viscosity is necessary when the cardiac output and peak blood velocity increase as a part of a sympathetic response or anemia, which occurs following significant hemorrhage. Blood viscosity, as reflected in systemic vascular resistance and vascular wall shear stress, is sensed, respectively, by cardiomyocyte stretching in the left ventricle and mechanoreceptors for wall shear stress in the carotid sinus. By controlling blood volume and red blood cell mass, the renin-aldosterone-angiotensin system and the systemic vascular resistance response control the hematocrit, the strongest intrinsic determinant of blood viscosity. These responses provide gross control of blood viscosity. Fine-tuning of blood viscosity in transient conditions is provided by hormonal control of erythrocyte deformability. The short half-life of some of these hormones limits their activity to specific vascular beds. Hormones that modulate blood viscosity include erythropoietin, angiotensin II, brain natriuretic factor, epinephrine, prostacyclin E2, antidiuretic hormone, and nitric oxide.

Investigating the blood rheology in the first trimester pregnancies with high risk for preeclampsia.

BACKGROUND: Pregnancy is a dynamic process associated with changes in vascular and rheological resistance. Maternal maladaptation to these changes is the leading cause of pregnancy complications such as preeclampsia. OBJECTIVE: This study aimed to assess the hemorheological alterations in pregnancies with a high risk for preeclampsia in the first trimester. METHODS: Ninety-two pregnant women were allocated into the high preeclampsia risk group (37 cases) and control groups (55 cases). Plasma and whole blood viscosity and red blood cell morphodynamic properties, including deformability and aggregation were assessed by Brookfield viscometer and laser-assisted optical rotational cell analyzer (LORRCA) at 11-14 gestational weeks. RESULTS: Whole blood viscosity was significantly higher in the high-risk group at all shear rates. Plasma viscosity and hematologic factors showed no differences between the groups. Hematocrit levels positively correlated with high blood viscosity only in the high-risk group. There were no significant changes in the other deformability and aggregation parameters. CONCLUSIONS: Changes in the whole blood viscosity of pregnant women with high preeclampsia risk refer to impaired microcirculation beginning from the early weeks of gestation. We suggest that the whole blood viscosity is consistent with the preeclampsia risk assessment in the first trimester, and its measurement might be promising for identifying high-preeclampsia-risk pregnancies.

Role of Plasma Membrane at Dielectric Relaxations and Intermembrane Interaction in Human Erythrocytes.

Dielectric relaxations at 1.4 MHz (ßsp) and 9 MHz (γ1sp) on the erythrocyte spectrin network were studied by dielectric spectroscopy using dense suspensions of erythrocytes and erythrocyte ghost membranes, subjected to extraction with up to 0.2% volume Triton-X-100. The step-wise extraction of up to 60% of membrane lipids preserved γ1sp and gradually removed ßsp-relaxation. On increasing the concentration up to 100 mM of NaCl at either side of erythrocyte plasma membranes, the ßsp-relaxation was linearly enhanced, while the strength of γ1sp-relaxation remained unchanged. In media with NaCl between 100 and 150 mM ßsp-relaxation became slightly inhibited, while γ1sp-relaxation almost disappeared, possibly due to the decreased electrostatic repulsion allowing erythrocytes to come into closer contact. When these media contained, at concentrations 10-30 mg/mL dextran (MW 7 kDa), polyethylene glycol or polyvinylpyrrolidone (40 kDa), or albumin or homologous plasma with equivalent concentration of albumin, the γ1sp-relaxation was about tenfold enhanced, while ßsp-relaxation was strengthened or preserved. The results suggest the Maxwell-Vagner accumulation of ions on the lipid bilayer as an energy source for ßsp-relaxation. While ßsp-relaxation appears sensitive to erythrocyte membrane deformability, γ1sp-relaxation could be a sensitive marker for the inter-membrane interactions between erythrocytes.

Zinc improved erythrocyte deformability and aggregation in patients with beta-thalassemia: An in vitro study.

BACKGROUND: Thalassemia patients have reduced red cell deformability and decreased plasma zinc levels in their blood. OBJECTIVE: This study aimed to evaluate the effects of zinc (Zn) on the hemorheological parameters and antioxidant enzyme activities in ß-thalassemia major (TM) and healthy volunteers (HV). METHODS: Hemorheological parameters were measured using LORCA (laser-assisted optical rotational cell analyzer) after adjusting the hematocrit to 40%. Zinc sulfate (ZnSO4.7H2O) was used for Zn incubation with a concentration of 0.5µg/dl. Oxidative stress and antioxidant status were determined using commercial kits. RESULTS: Data showed that after Zn incubation, EImax, the area under the EI-osmolarity curve (Area), and Omax decreased in TM. However, no significant difference was observed in the osmotic deformability parameters of HV. The increased elongation index was obtained at different shear stresses for TM and HV, and SS1/2 decreased in both groups. The AMP and aggregation index (AI) decreased in TM, and the required time for half of the maximum aggregation (t1/2) increased in HV. However, Zn did not affect oxidative parameters in both groups. CONCLUSIONS: This study showed that Zn incubation increased deformability and decreased aggregation in thalassemic erythrocytes. It means that Zn supplementation will contribute to microcirculation in thalassemia patients.

Determination of the erythrocyte sedimentation rate using the hematocrit-corrected aggregation index and mean corpuscular volume.

BACKGROUND: Determination of the erythrocyte sedimentation rate (ESR) by measurement of erythrocyte aggregation is an alternative to the Westergren method and can be performed rapidly. However, its principle is opaque and the ESR values obtained can deviate from Westergren method values (WG ESR) due to hematocrit. Furthermore, WG ESR is affected by particle size, but no studies have examined the effect of individual mean corpuscular volumes (MCVs). METHODS: Simultaneous measurement of the erythrocyte aggregation index (AI) over a 5-s interval and determination of the complete blood count in 80 µL blood from 203 patients were performed (hematocrit, 21.4%-52.3%; MCV, 62.7-114.1 fL). ESR values were calculated with the hematocrit-corrected AI (HAI) for comparison with WG ESR. We improved the calculation formula by using MCV. RESULTS: The sedimentation velocity of a single erythrocyte in the samples agreed well with an exponential function of HAI. ESR values calculated using HAI showed excellent correlation with WG ESR (r = 0.899, p < 0.001; Bland-Altman analysis: bias 2.76, limits of agreement (LOA) -24.5 to 30.0), but the difference between the calculated ESR and WG ESR increased with decreasing MCV. Calculation of ESR considering both HAI and MCV eliminated the MCV-dependent deviation and improved the correlation with WG ESR (r = 0.920, p < 0.001, bias -2.17, LOA -24.6 to 20.3). CONCLUSION: Calculation using HAI and MCV can rapidly provide ESR values that are highly correlated with WG ESR in clinical specimens over a wide range of hematocrit and MCV values.

Axial shear rate: A hemorheological factor for erythrocyte aggregation under Womersley flow in an elastic vessel based on numerical simulation.

Erythrocyte aggregation (EA) is a highly dynamic, vital phenomenon to interpreting human hemorheology, which would be helpful for the diagnosis and prediction of circulatory anomalies. Previous studies of EA on erythrocyte migration and the Fåhraeus Effect are based on the microvasculature. They have not considered the natural pulsatility of the blood flow or large vessels and mainly focused on shear rate along radial direction under steady flow to comprehend the dynamic properties of EA. To our knowledge, the rheological characteristics of non-Newtonian fluids under Womersley flow have not reflected the spatiotemporal behaviors of EA or the distribution of erythrocyte dynamics (ED). Hence, it needs to interpret the ED affected by temporal and spatial flow variation to understand the effect of EA under Womersley flow. Here, we demonstrated the numerically simulated ED to decipher EA's rheological role in axial shear rate under Womersley flow. In the present study, the temporal and spatial variations of the local EA were found to mainly depend on the axial shear rate under Womersley flow in an elastic vessel, while mean EA decreased with radial shear rate. The localized distribution of parabolic or M-shape clustered EA was found in a range of the axial shear rate profile (-15 to 15s-1) at low radial shear rates during a pulsatile cycle. However, the linear formation of rouleaux was realized without local clusters in a rigid wall where the axial shear rate is zero. In vivo, the axial shear rate is usually considered insignificant, especially in straight arteries, but it has a great impact on the disturbed blood flow due to the geometrical properties, such as bifurcations, stenosis, aneurysm, and the cyclic variation of pressure. Our findings regarding axial shear rate provide new insight into the local dynamic distribution of EA, which is a critical player in blood viscosity. These will provide a basis for the computer-aided diagnosis of hemodynamic-based cardiovascular diseases by decreasing the uncertainty in the pulsatile flow calculation.

Erythrocyte aggregation in sudden flow arrest is linked to hyperthermia, hypoxemia, and band 3 availability.

BACKGROUND: Erythrocyte aggregation is a phenomenon that is commonly found in several pathological disease states: stroke, myocardial infarction, thermal burn injury, and COVID-19. Erythrocyte aggregation is characterized by rouleaux, closely packed stacks of cells, forming three-dimensional structures. Healthy blood flow monodisperses the red blood cells (RBCs) throughout the vasculature; however, in select pathological conditions, involving hyperthermia and hypoxemia, rouleaux formation remains and results in occlusion of microvessels with decreased perfusion. OBJECTIVES: Our objective is to address the kinetics of rouleaux formation with sudden cessation of flow in variable temperature and oxygen conditions. METHODS: RBCs used in this in vitro system were obtained from healthy human donors. Using a vertical stop-flow system aligned with a microscope, images were acquired and analyzed for increased variation in grayscale to indicate increased aggregation. The onset of aggregation after sudden cessation of flow was determined at proscribed temperatures (37-49°C) and oxygen (0%, 10%), and in the presence and absence of 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS). Both autologous and homologous plasma were tested. RESULTS: RBCs in autologous plasma aggregate faster and with a higher magnitude with both hyperthermia and hypoxemia. Preventing deoxyhemoglobin from binding to band 3 with DIDS (dissociates the cytoskeleton from the membrane) fully blocks aggregation. Further, RBC aggregation magnitude is greater in autologous plasma. CONCLUSIONS: We show that the C-terminal domain of band 3 plays a pivotal role in RBC aggregation. Further, aggregation is enhanced by hyperthermia and hypoxemia.

Sex-differential downregulation of methotrexate on plasma viscosity and whole blood viscosity in psoriasis.

BACKGROUND: Psoriasis is associated with an increased risk for cardiovascular disease (CVD). Methotrexate (MTX) is often used as a first-line system therapy and there is a need to determine its effect on whole blood viscosity (WBV) and plasma viscosity (PV) in psoriasis.METHODSA prospective, single-center, interventional study with a total of 111 psoriatic patients who received MTX therapy from October 22, 2018, to December 28, 2019, and 111 age- and sex-matched healthy controls. Changes in WBV, PV, blood counts, liver and renal function were evaluated.RESULTSPsoriatic patients had significantly higher levels of WBV and relative viscosity (RV) at low shear rate (LSR), erythrocyte aggregation index (EAI), and PV than sex and age-matched healthy controls. PV was positively correlated with erythrocyte sedimentation rate (ESR), ESR was positively correlated with high sensitive C-reactive protein (hCRP). But only hCRP was positively associated with psoriasis area severity index (PASI) score. MTX significantly decreased the levels of PV, ESR, hCRP, and blood pressure (BP) in male patients, and the level of WBV in female patients. CONCLUSION: Sex-specific downregulation of MTX on WBV, PV, hCRP, and BP, indicating that the effect of MTX on the risk of cardiovascular disease was related with sex.

Hemorheology and oxidative stress in patients with differentiated thyroid cancer following I-131 ablation/metastasis treatment.

BACKGROUND: Although radioiodine theraphy (RAIT) is thought to affect blood cells and oxidative stress, hemorheological alterations following dose-dependent RAIT remains unknown. OBJECTIVE: The aim of this study was to determine the effects of RAIT on hemorheological and oxidative stress parameters in patients with differentiated thyroid cancers (DTC). METHODS: Totally 31 DTC patients (mean age 46.32±11.15 years) and 26 healthy controls (mean age 50.50±6.22 years) were included. Venous blood samples were collected from each patient before and after treatment (7th day, 1th month and 6th month). Erythrocyte aggregation-deformability and oxidative stress parameters were determined. p < 0.05 was considered as statistically significant. RESULTS: Erythrocyte deformability of the patients determined at 16.87 and 30 Pascal were significantly lower than healthy individuals. Erythrocyte aggregation index (AI) of the patients was higher, whereas erythrocyte aggregation half-time (t½) was lower compared to control. Erythrocyte deformability values and AI were not significantly different from the pre- and post-radioiodine treatment groups. There was no statistically significant difference between the oxidative stress parameters before and after the treatment. CONCLUSIONS: Patients were in a worse hemorheological condition compared to healthy individuals. After RAIT, RBC deformability and aggregation were not affected and no significant change in oxidative stress parameters was detected.

Pilot clinical study of quantitative ultrasound spectroscopy measurements of erythrocyte aggregation within superficial veins.

BACKGROUND: An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE: This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS: Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S10). RESULTS: W and Din vivo measurements were positively correlated with the ex vivoS10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS: We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

Larvas recién nacidas de Trichinella spiralis: cinética de agregación eritrocitaria / Newborn larvae of Trichinella spiralis: erythrocyte aggregation kinetics

El objetivo de este trabajo fue estudiar la cinética de agregación eritrocitaria producida por dos concentraciones de larvas recién nacidas (LRN) de Trichinella spiralis. Se trabajó con 5 suspensiones eritrocitarias incubadas con 500 y 1.000±100 LRN/mL durante 120 minutos, con tomas de muestra al tiempo inicial y cada 15 minutos. Los respectivos controles se incubaron de la misma manera con solución salina. Se aplicaron el método de titulación por Polibrene calculando el CexpST y la técnica de análisis de la variancia con las comparaciones múltiples según Tukey. Los resultados mostraron para ambas concentraciones de LRN, que el coeficiente promedio disminuyó con el aumento del tiempo de incubación. En el tratamiento con 1.000 LRN/mL, el coeficiente promedio no presentó diferencias significativas a tiempo 0 y 15 minutos, ni entre 60 y 75 minutos, mientras que con 500 LRN/mL no hubo diferencias entre los tiempos 0, 15 y 30 minutos. Todas las restantes diferencias fueron significativas para ambas concentraciones larvales. El valor promedio de CexpST no difirió significativamente entre los dos tratamientos a tiempo 0 y 15 minutos, pero a todos los otros tiempos fue menor a mayor concentración de larvas. La experiencia realizada indicaría que in vivo, la cantidad de LRN y el tiempo que permanecen en circulación determinan el grado de desializacion eritrocitaria, y por lo tanto el riesgo de activación T y de alteraciones hemorreológicas en el hospedador.

The aim of this work was to study the kinetics of erythrocyte aggregation produced by two concentrations of Trichinella spiralis newborn larvae (NL). Work was performed with 5 erythrocyte suspensions incubated with 500 and 1000 ± 100 NL/mL for 120 minutes, taking samples at the initial time and every 15 minutes. The respective controls were incubated in the same way with saline solution. The Polybrene titration method calculating the CexpST and the variance analysis technique with the multiple comparisons according to Tukey were applied. The results showed that the average coefficient decreased with the rise in incubation time for both NL concentrations. The average coefficient did not present significant differences between the initial time and 15 minutes, nor between 60 and 75 minutes in the treatment with 1000 NL/mL, while there were no differences between 0,15 and 30 minutes in the treatment with 500 NL/mL. All other differences were significant for both larval concentrations. The average value of CexpST did not differ significantly between the two time treatments at zero time and 15 minutes, but at all other times it was less at a higher concentration of larvae. The experience carried out would indicate that in vivo, the amount of NL and the time that they remain in circulation determines the degree of erythrocyte desialylation, and therefore, the risk of T activation and hemorrheological alterations in the host.

O objetivo desse trabalho foi estudar a cinética de agregação eritrocitária produzida por duas concentrações de larvas recém nascidas (LRN) de Trichinella spiralis. O trabalho foi feito com 5 suspensões eritrocitárias incubadas com 500 e 1.000 ± 100 LRN/mL por 120 minutos, colhendo amostras no tempo inicial e a cada 15 minutos. Os respectivos controles foram incubados da mesma forma com solução salina. Foi aplicado o método de titulação por Polibreno e se calculou CexpST. e a técnica de análise da variância com as comparações múltiplas de acordo com Tukey. Os resultados mostraram, para ambas as concentrações de LRN, que o o coeficiente médio diminuiu com o aumento do tempo de incubação. No tratamento com 1.000 LRN/mL o coeficiente médio não mostrou diferenças significativas no tempo 0 e 15 minutos ou entre 60 e 75 minutos, ao passo que não houve diferenças com 500 LRN/mL entre tempos 0, 15 e 30 minutos. Todas as restantes diferenças foram significativas para ambas as concentrações de larvas. O valor médio de CexpST não diferiu significativamente entre os dois tratamentos no tempo de 0 e 15 minutos, mas em todos os outros tempos foi menor em maior concentração de larvas. A experiência realizada indicaria que in vivo a quantidade de LRN e o tempo que permanecem em circulação determina o grau de dessialização dos eritrócitos e, portanto, o risco de ativação T e de alterações hemorreológicas no hospedeiro.

Effects of Ankaferd Hemostat on red blood cell aggregation: a hemorheological study

Background/aim: Ankaferd hemostat (ABS; Ankaferd blood stopper, Istanbul, Turkey) is a prohemostatic agent affecting erythrocytes. The hemostatic action of ABS depends upon fibrinogen gamma chain, prothrombin, and red blood cells. The aim of this study was to assess the effects of ABS on erythrocyte aggregation via hemorheological analyses. Materials and methods: To measure erythrocyte aggregation, blood samples were obtained from healthy, nonsmoker volunteers who had not taken any medication in the previous 10 days. One mL of blood was placed into the laser-assisted optical rotational cell analyzer (LORCA), into the chamber formed by the gap between two concentric glass cylinders. The solution prepared with ABS and saline was added to blood in incremental amounts of 10 µL, 20 µL, 30 µL, 40 µL, 50 µL, 60 µL, 70 µL, and 100 µL. Erythrocyte aggregation was determined by laser-assisted optical rotational cell analyzer at 37 °C Results: AMPwas found to be 17.7 ± 2.1 au in the blood without ABS, whereas it was lower in the blood with ABS. AMP was 16.0 ± 3.3 in the ABS-added blood group. RBC aggregates did not form faster when cells contacted ABS. The t t½ value was 4.6 ± 2.6 in the ABS-added blood group and 1.9 ± 0.20 in the control group. Aggregation was faster in the control group (P = 0.03). AI, which is a combination of AMP and t½, was lowered in the ABS group (48.7 ± 12.3) compared to the control group (65.8 ± 1.6) (P = 0.02). It was notable that the γIsc max (sec-1) value of the control was higher (200 ± 106) than the ABS-added blood group (141 ± 51.0). Conclusion: ABS has antierythroid aggregation effect. ABS inhibits pathological aggregation of red blood cells. Antithrombotic clinical effects of ABS may be ascribed to the antierythroid aggregan actions of the drug.

Effects of two selected SSRIs on hemorheological parameters in rats.

BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants commonly used in cardiovascular diseases (CVDs), inhibit the re-uptake of serotonin not only into neurons but also into platelets. Hence they increase the level of serotonin in plasma. OBJECTIVE: This study was aimed to clarify the effects of two selected SSRIs on plasma serotonin level, hemorheological parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity) and selected oxidative stress markers (MDA, GSH, GSSG levels in plasma and erythrocytes). METHODS: Two different SSRIs (Fluvoxamine and Sertraline) were administered to male Sprague-Dawley rats in acute (5 days) or chronic fashion (21 days) at 20 mg/kg/day dose. RESULTS: Aggregation amplitude (AMP) decreased significantly in the chronic sertraline and acute fluvoxamine groups; aggregation half time (t1/2) decreased significantly in the chronic fluvoxamine group. Biochemical parameters indicating oxidative stress significantly increased in the chronic sertraline group. CONCLUSIONS: Since SSRI's are commonly used in patients with CVDs, complementary studies are needed to assess the impact of such changes in hemorheological parameters on the risk for CVD, and to reveal the effects of other SSRIs on hemorheological parameters.

Investigation of the effects of major ozone autohemotherapy application on erythrocyte deformability and aggregation.

BACKGROUND: Ozone is used intensively worldwide in treatment and research of various pathologies due to its healing effects. OBJECTIVE: The aim of this study is to investigate the effect of major ozone autohemotherapy on erythrocyte deformability and aggregation. METHODS: 10 and 50µg/ml doses of ozone was applied for 20 minute to venous blood samples obtained from 10 healthy male volunteers. Erythrocyte aggregation, deformability were measured by an ektacytometer. Total oxidant status, total antioxidant status were measured via a commercial kit. The oxidative stress index was calculated. RESULTS: Ozone at 10 and 50µg/ml doses did not alter erythrocyte aggregation. 50µg/ml ozone increased red blood cell (RBC) deformability measured at 0.53 Pa. Compared with the Control value, there was a significant increase in TOS, TAS for the doses of 10 and 50µg/ml. The increase in TAS was found to be more significant at 10µg/ml dose. The most obvious increase in OSI value was observed at 50µg/ml. CONCLUSION: Our results demonstrate that although 10µg/ml ozone has no effect on hemorheology, 50µg/ml ozone concentration has positive effects on RBC deformability, thus circulation at 0.53 Pa corresponding to the shear stress encountered during venous circulation.

Hemorheological alterations following an acute bout of nordic hamstring exercise in active male participants1.

BACKGROUND: The Nordic hamstring exercise (NHE) has been proven to be an effective preventive technique for hamstring injuries. Hemorheological parameters (erythrocyte deformability and aggregation) play a critical role in exercise influencing oxygenation. Although previous studies presented hemorheological alterations induced by different types of exercise, changes in red blood cell (RBC) deformability and aggregation following NHE remain unknown. Present study was designed to explore possible alterations in hemorheological and oxidative parameters after an acute bout of NHE. METHODS: 10 healthy, male, active students (mean age 19.9±0.23, BMI: 21.56±0.54) participated to the study. They performed a single session of seven-repetitions of NHE followed by a familiarisation period. Blood samples were obtained before and immediately after the exercise from the antecubital vein. Hemorheological parameters were measured by an ektacytometer. RESULTS: NHE did not change deformability, hematocrit and oxidative stress but, increased RBC aggregation index (AI, p = 0.011) and decreased RBC aggregation half time (t½, p = 0.009). CONCLUSIONS: Our results suggest that, increased RBC aggregation following an acute bout of NHE may result in increased plasma skimming and thus ease the flow of blood.

Impaired Blood Rheology in Pulmonary Arterial Hypertension.

BACKGROUND: Understanding of the pathophysiologic manifestations of pulmonary arterial hypertension (PAH) is still evolving. The aims of the present study were to determine the alterations in blood rheology, and to investigate the relationship between those alterations and laboratory parameters in PAH. METHODS: The study included 21 consecutive treatment-naive patients with PAH and 32 age and sex-matched healthy controls. Patients were categorised in class II (n=6), class III (n=13), and class IV (n=2). All subjects underwent right-heart catheterisation. Erythrocyte deformability and aggregation were measured by an ektacytometer. RESULTS: Haemodynamic variables were as follows: the mean right atrial pressure: 9.94±5.76mmHg; the average pulmonary vascular resistance: 5.66±3 WU; Fick cardiac index: 4.15±2.75l/min/m2; and mixed venous O2 saturation: 64.59±12.53%. The average 6-minute walk distance was 351.09±133.08m. Erythrocyte deformability measured at 0.95, 3.00, and 5.33Pa was significantly lower, erythrocyte aggregation index (AI) was higher, and aggregation half-time (t1/2) was lower in PAH. AI and fibrinogen were positively correlated with NT pro-BNP (AI-NT pro-BNP: r=0.579; fibrinogen-NT pro-BNP: r=0.591). t1/2 was negatively correlated with NT pro-BNP (t1/2-NT pro-BNP: r=-0.648). CONCLUSIONS: The increase in erythrocyte aggregation and the decrease in deformability may theoretically increase the flow resistance and may be of haemodynamic significance. The association between erythrocyte aggregation and NT pro-BNP may indicate that erythrocyte aggregation increases with disease progression. These alterations contribute to the understanding of the pathophysiology and could serve as markers of disease presence.

Alterations of the erythrocyte membrane by in vitro action of Trichinella spiralis muscle larvae.

The complex life cycle of Trichinella spiralis includes the migration of newborn larvae through the bloodstream to their encystment in muscle. The parasite establishes an intimate contact with the erythrocytes of the host both during the migration of the newborn larvae and when encysting, as this parasite causes intense vascularization in the muscle cell. The goal of this work was to study the effects of various concentrations of T. spiralis muscle larvae (ML) on erythrocyte membranes. The treatment was performed by incubating human erythrocytes with equal volume of different concentrations of ML for 30 minutes, with controlled agitation (37°C). The control erythrocytes (with no contact with the larvae) were incubated in the same way with an equal volume of physiological solution. To evaluate the alterations to the erythrocytes by the action of the larvae and in the respective controls, an Erythrocyte Rheometer and a Digital Image Analysis technique were used. The results indicated that when the larval concentration was higher, the aggregation and erythrocyte membrane alterations were also higher. Also, the erythrocyte deformability index and the erythrocyte elasticity increased. The values of isolated cell coefficient varied from 0.51 in the treatment with 100 larvae/ml to 0.91 in the incubation with 1000 larvae/ml. This experiment shows that T. spiralis muscle larvae affect significantly the red blood cell aggregation and the erythrocyte viscoelastic properties.

A Single Bout of Exercise Reduces Postprandial Lipemia but Has No Delayed Effect on Hemorheological Variables.

High plasma triglyceride (TG) concentration in fasting state could cause hemorheological abnormality, thus increasing the incidence of metabolic diseases. Exercise has been reported to effectively reduce postprandial TG response. This study aimed to investigate whether a single bout of pre-prandial exercise can affect lipemia and hemorheological variables after a high-fat meal. Nine healthy young male subjects completed two experimental trials. The subjects walked for 1 h at 50% maximal oxygen uptake (V̇O2max) (the exercise, EX trial), or rested (the control, CON trial). In the next morning, the subjects consumed a high-fat meal, and the postprandial lipemia and hemorheological responses were monitored for 6 h. The results showed that postprandial plasma TG concentrations were significantly lower in the EX trial compared to the CON trial. The postprandial low-density lipoproteins (LDL) concentration declined in the first 2 h and then gradually returned to the baseline level in both trials. The postprandial blood viscosity also decreased in the CON trial. There was no significant difference in postprandial blood viscosity, red blood cell (RBC) deformation index and aggregation degree between the trials. There was no significant correlation between plasma TG concentration and blood viscosity. In conclusion, brisk walking effectively reduced postprandial TG concentration, but has no significant impact on postprandial blood viscosity, RBC deformation index and RBC aggregation index.

Inhibition of PAI (Plasminogen Activator Inhibitor)-1 Improves Brain Collateral Perfusion and Injury After Acute Ischemic Stroke in Aged Hypertensive Rats.

Background and Purpose- Aging and hypertension, comorbidities prevalent in the stroke population, are associated with poor collateral status and worsened stroke outcome. However, underlying mechanisms by which these conditions affect stroke outcome are not clear. We studied the role of PAI (plasminogen activator inhibitor)-1 that is increased in aging and hypertension on brain and vascular expression of inflammatory factors and perfusion that may contribute to worse stroke outcomes. Methods- Aged (≈50 weeks) and young (≈18 weeks) spontaneously hypertensive rats (SHR) were subjected to ischemia by middle cerebral artery occlusion (2 hours) and reperfusion (2 hours) with or without treatment with the PAI-1 inhibitor TM5441. Changes in middle cerebral artery and collateral perfusion territories were measured by multisite laser Doppler. Reactivity to TM5441 was studied using isolated and pressurized leptomeningeal anastomotic arterioles. Brain injury was determined by 2,3,5-triphenyltetrazolium staining and quantitative immunohistochemistry of amyloid-ß-42, PAI-1, and hemoglobin. Circulating inflammatory factors were measured by ELISA. Results- Changes in cerebral blood flow during middle cerebral artery occlusion were similar between groups, with both having poor collateral perfusion and incomplete reperfusion. However, aged SHR had greater brain injury versus young (41±2 versus 23±2%, P<0.05) as well as increased brain deposition of amyloid-ß-42 and circulating oxLDL (oxidized low-density lipoprotein). Erythrocyte aggregation and hemorrhage within the injured brain was observed in 50% of aged but no young SHR, with increased circulating PAI-1 in this subgroup of aged SHR (16±3 versus 6±2 ng/mL, P<0.05). PAI-1 inhibition with TM5441 improved brain injury but did not affect hemorrhage. TM5441 increased collateral perfusion by 38±7% and dilated leptomeningeal anastomotic arterioles by 44±10%, which was abolished by nitric oxide synthase inhibition. Conclusions- Increased injury in aged SHR seemed to be related to poor collateral perfusion, hemorrhagic transformation, increased amyloid-ß-42, and oxidative stress. PAI-1 inhibition reduced infarction in both groups of SHR that possibly due, in part, to increased collateral perfusion.