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The word "Biorheology" was introduced in 1948 during the first international congress on Rheology but "hemorheology" was first employed in 1951 during a meeting of the American Institute of Physics. Basically this science is related to physics and mechanics. The first international conference devoted to hemorheology was organized by AL Copley in Reykjavik (Iceland) in July 1969 and an International Society on Hemorheology was created. But after Reykjavik this society was named "International Society of Biorheology". The term "Clinical Hemorheology" was proposed in Nancy in 1979 which was named "First European Symposium on Clinical Hemorheology" and an European Coordinating Committee on Clinical Hemorheology (ECCCH) was created. The European Society on Clinical Hemorheology and Microcirculation was in fact created in Frankfurt in 1990 initiated by Albrecht Ehrly. In Nancy it was also decided to create a European Award named "Fahraeus Medal". After Nancy, the ECCCH and the European Society organized symposia in London, Baden Baden, Sienna, Frankfurt, Bordeaux,  ...  , Sofia  ...   and now Lisboa. Now it is necessary to give new directions for the development of Hemorheology and Clinical Hemorheology. Different ways can be considered:-Development of new theoretical models which take into account the heterogeneity of blood and blood vessel-Research on cell mechanobiology and mechanotransduction (leucocyte, endothelial and smooth muscle cells)-Study of cellular interactions (aggregation, adhesion,  ...) and intracellular transport-Membrane rheology and concept of molecular fluidity-Dynamic blood coagulation in relation with molecular reactions-Development of metrology for clinical hemorheology.

Almost all of the cells of the human body are subjected to mechanical stresses. In endothelial cells, mechanical stresses can vary from some milli-Pascal (shear stress) to one ore more Pascal (hydrostatic pressure). Now it is know that mechanical stresses have a decisive part cellular physiology. However, if the main biological effects of mechanical stress are well related, the mechanisms allowed the relation between mechanical stress to physiological phenomenon remain nearly unknown (mechanotransduction phenomenon). In this work, through personal results and published works, the authors considers all the effects of mechanical stresses and the possible hypothesis., (Copyright 2004 IOS Press)

The vascular endothelium is a biologically active monolayer of cells providing an interface between the blood flow and tissues. Vascular Endothelial Cells (VEC) have two functional states. The endothelium is normally anti-thrombotic and anti-adhesive to ensure blood fluidity. During aggressions, such as atherosclerosis, inflammation states, metabolic diseases (through chemical or mechanical stimuli), VEC can reverse its functions by expressing stored material or by slower involvement of previously are repressed genes. Endothelial cells have three types of anti-thrombotic properties: vaso regulating properties: VEC release vasomotor components, such as endothelin (vasoconstriction), prostacyclin and nitric oxide, (vasodilatation). Endothelial cells also have antithrombotic and hemostatic properties. They express proteoglycans on their surface, including some negative-charge, plasminogen, sulfate glycosaminoglycans (heparan-sulfate), and secrete plasminogen tissular activator (t-PA) and tissular factor inhibitor. One fundamental action of the endothelium in that area is the production and expression of thrombomodulin, a thrombin receptor. This function has a major anticoagulation effect, controlling continual thrombin generation at the sub-endothelium and blood cell interface. Moreover, endothelial cells show anti-adhesion properties. During cardio-vascular diseases, all of these properties may be reversed. Thus the VEC have a determinant role in hemodynamic control through these various metabolic activities, such as control of homeostasis, vascular tone, blood fluidity, coagulating properties, cellular adhesion. Otherwise, many studies have demonstrated that local blood flow conditions have a crucial role on the VEC properties (mechanoactivation and mechanotransduction concept). In conclusion, knowledge of all the properties of the endothelial cells and control of the phenomena which define their functions is a key element in understanding cardiovascular diseases.

The aim of this work was to evaluate a new automatic cone-plate viscometer (LBY-N6, PRECIL, Beijing, China) which was designed for clinical measurements of blood and plasma viscosities. Standard calibrating oils of viscosity varying from 1.85 to 20.5 mPas (conforming to ASTM Standard) were used to test the precision and reproducibility of the device. Then the viscometer was used to measure blood and plasma viscosities. The results were compared with those obtained with a conventional Couette viscometer and a capillary viscometer. The results showed that this new viscometer gave good values of viscosity for standard oils with relative errors lower than 10% at shear rates ranging from 20 to 200 s(-1). It also had a good reproducibility (standard deviations < 3% in most cases). Only the results at low shear rates (< 10 s(-1)) were less identical. As for blood, the relative difference between the results given by LBY-N6 and those obtained by Low Shear 30 was less than 10% at high shear rates. This difference decreased with shear rate and could be partly caused by viscoelastic and thixotropic properties of human blood. A small difference between the values of plasma viscosity obtained by LBY-N6 and the capillary viscometer AMTEC was also observed. In conclusion, this new viscometer can be used a routine tool to determine quickly plasma and blood viscosities in clinical practice at shear rates higher than 20 s(-1).

Rheological parameters (plasma and blood viscosities, erythrocyte aggregation and deformability) are very relevant to a better understanding of the changes inflicted on the properties of blood in various hematological diseases (monoclonal gammopathies in particular). This study reports the measurement of rheological parameters (plasma and blood viscosity, RBC aggregation and deformability) in hematological disorders where abnormal blood properties have been described. All these diseases are treated by means of blood separators (therapeutic haemapheresis:plasma exchange, plasma processing, or erythrocyte exchange). We monitored plasma viscosity in 50 patients with monoclonal gammopathies: before and after each exchange (PE) or plasma processing (PP) sessions. Hyperviscosity was reduced in all cases after plasma exchange. Erythrocyte aggregation in gammopathies was also tested (15 multiple myelomas) treated by PE or PP, EA abnormalities and therapy-induced changes are described. EA is also modified by erythropheresis (seven sickle cell anemias). Measurement of rheological parameters are useful to the diagnosis of rheological abnormalities, as well as to assess the impact of therapeutic hemapheresis techniques like plasma exchange, plasma treatment, erythrocytapheresis.

The application of principles of hemorheology on a process of blood coagulation was suggested by H.H. Hartert - inventor of the thromboelastograph which he introduced in 1947. These principles of applying of a mechanical force and detecting the response of coagulating blood enable to determine a functional evidence of the physiological process producing a hemostatic clot. The thromboelastography, as well as other rheological techniques used for this determination, are introduced evaluating the process in terms of the rate of coagulation, clot elasticity, deformability and permeability. Recent applications of the techniques to the diagnosis of disorders of hemostasis and the study of drug effects on coagulation are presented as well.

Energy evolved from hemagglutination reaction or spent in dissociating erythrocyte agglutinates has been proved to be an excellent parameter for analyzing cell-cell interactions mediated by bridging molecules such as antibodies or lectins. We developed a new rheo-optical method to estimate the energy of dissociation of red blood cell agglutinates. In a Couette shear field agglutinates can be dissociated until a suspension of monodispersed cells is obtained. Intensity of light backscattered by suspended agglutinates increases during their mechanical dissociation. Variation of backscattered light intensity correlates with the energy spent in the process. The adhesive energy of erythrocyte agglutination induced by lectins has been estimated by applying this method. Two specific lectins (Dolichus Biflorus agglutinin and Ulex Europaeus agglutinin) and a new lectin obtained from Amarantus Cruentus seeds which specificity is unknown were studied. Results obtained in this work for Dolichus Biflorus lectin are comparable with values published by other authors. An asymptotic decrease of adhesive energy was observed when the mechanical dissociation was applied several times on the same sample. Our results suggest that the cell detachment is accompanied by the extraction of membrane receptors. This finding is consistent with results obtained by other authors.

There is a need for quality assurance procedures in hemorheology, especially for clinical and pharmacological studies, which require reliable and well-calibrated instruments to be interpretable and comparable. Preliminary investigations allowed preparation of standardized SM (normal NS and hyperaggregable HS), and checking of storage conditions (in accordance with the guidelines of the SSC of ISTH) of RBC in nutritive SAG mannitol for at least 2 or 3 weeks with subsequent washings and resuspension in SM. In our study, we compared erythro-aggregometers of the same brand in 6 laboratories, using the same red blood cells (RBC) and suspending media (SM) for each series of tests. EA was measured by laser backscattering with determination of aggregation time (AT), partial dissociation threshold (PDT) and aggregation index (AI). Prior to the study, devices were set up on the same day with the same standardized blood, and calibration data were then analyzed. Within-assay precision (WAP) was assessed on 3 days for the 2 types of SM (n = 18 x 2). Between-assay precision (BAP) was assessed on 6 occasions, once every month (n = 6 x 2 x 6). Accuracy was studied with 3 series of RBC resuspended in 10 SM of "unknown" aggregability. Good agreement was observed between 5/6 centers for the 3 parameters of EA. WEP was good: CV of AT ranging from 1.4 to 2.5% for the NS and from 1.4 to 2.4% for the HS. In each center, BAP was slightly lower than WEP (CV: 8-11.8% for the NS and 3.8-4.7% for the HS over the 6-month study), with no drift, except for one center. Precision was always better with the HS than with the NS which seemed a better tool to assess it. As to accuracy, non-significant differences were generally found between centers, with similar data to the reference values. This work also stressed the importance of the RBC parameter itself in rheological data. For the first time, a protocol for standardization of EA has been developed and evaluated, permitting the Quality Control of this technique.

Harvey may be considered to be the precursor of modern hemorheology, but it was not until the pioneering work of Loewenhoeck, Poiseuille, Fahraeus and Copley that the essential role of the hemorheological properties of blood and its cellular components was recognized. Before the advent of modern hemorheology in the 70s, studies were mainly focussed on microcirculation and validation of global hemorheological equations applied to blood circulation. Parallel studies on the microrheological properties (erythrocyte deformability and aggregation) explained analytically the non-Newtonian behavior of blood, and the essential contribution of these parameters to the understanding hyperviscosity syndromes. The development of clinical hemorheology in fact started at the international conferences held in Reykjavik (1966) and Heidelberg (1969), and with the initiation of the periodical European Microcirculation (since Nancy in 1960) and Clinical Hemorheology (since Nancy in 1979) Conferences. The current main avenues of research involve flow modelling, studies of cell-cell interaction mechanisms (aggregation and adhesion), in relation to the associated pathophysiological phenomena, such as cellular activation (platelets and leukocytes in particular), gene expression linked to blood flow (e.g. endothelial cells)... Clinically and therapeutically, it is crucial that pathophysiological studies be undertaken on the relationship existing between rheological parameters and objective clinical data (local flow rates, ischemic markers, hemostatic parameters, tissue oxygen, clinical symptoms,...). The main clinical application fields are cardiovascular diseases, thrombosis, diabetes, hypercholesterolemia... Also, studies on new therapeutics or on biomaterials should also be given priority.

Interactions between blood cells in the form of cellular aggregates or adhesion are observed in a variety of normal and pathological conditions. Aggregation of erythrocytes or platelets, adhesion of platelets and leucocytes and immune agglutination of RBC are examples of interactions involving blood cells. Cell adhesion and aggregation are modulated by specific interactions (antigen-antibodies reactions, adhesive macromolecules interactions...) or non-specific (van der Waals forces, electrostatic interactions, molecular bridgings...). These interactions may result in morphological and structural changes, or polarization phenomena. At the dynamic level, cellular adhesion (or aggregation) can divided in 4 main steps: transport, cellular activation (endogenous or exogenous), morphological, physical or steric rearrangements, contact (intercellular or on an artificial surfaces). It will be the nature of the interactions involved in these steps that will determine the binding cohesion and kinetic. In this paper, different types of interactions and the regulation mechanisms of adhesion and aggregation phenomena involved in blood hemodynamics will be summarized and some examples (RBC or platelets aggregation; platelets or leucocytes adhesion) will illustrate the importance of these phenomena in clinical hemorheology.

The influence of haemodialysis (HD) was assessed in 72 patients, undergoing a thrice weekly routine HD for chronic renal failure (CRF). Some of them received human recombinant erythropoietin (Eprex). Measurements were performed before and after the HD session: the erythrocyte aggregation (EA) was carried out by a laser backscattering technique with determination of the aggregation time (AT) and of the dissociation thresholds. Plasma viscosity (PV) was evaluated in an automatic capillary viscometer. Fibrinogen (Fg) levels, haematological features (blood cell count), serum proteins, creatinine, and some other biochemical parameters, were also determined. Anaemia was a common feature. Our results compared to those of a control group, confirmed the erythrocyte hyperaggregation before HD which increased during HD. PV also elevated before HD, further increased after HD; the same finding was observed for Fg. Some of these results might be related to the haemoconcentration. Significant correlations were noted between AT and PV, AT and Fg with closer correlations after HD, suggesting a strong cohesion of RBC aggregates, which enhanced during HD. Correlations were highly significant between relative variations of AT and relative variations of PV, Fg, proteins and body weight, before and after HD. Special attention was given to the group of patients under long term treatment with Eprex compared to non-treated dialysed patients: no significant difference was found between both groups. Our results are in agreement with a blood and plasma viscosity syndrome due to increased EA and with a tendency, to thrombosis reported in those patients.

Disturbances in hemostatic and hemorheological parameters have been investigated in a group of 29 children with nephrotic syndrome: 23 children classified as steroid-sensitive and 6 as steroid-resistant. Studies were performed before prednisone treatment and 3 weeks later, after initiation of steroid therapy. Before treatment, the alterations in hemostatic system involved moderate thrombocytosis with spontaneous aggregation in 19 patients. High levels of fibrinogen, factor VIII, Willebrand factor, protein C, protein S and alpha 2-macroglobulin (alpha 2M) were observed. Factor XII and alpha 1-antitrypsin (alpha 1AT) were lower than normal. Antithrombin III (ATIII) level was normal in the majority of patients. A plasma and blood hyperviscosity syndrome was also observed as well as an increase in erythrocyte aggregation. During treatment, an improvement in the hemostatic parameters was observed in the patients who responded to prednisone. The expected increase in factor VIII (frequently described in the literature) was not observed, while there was a significant increase in protein C. In the steroid-resistant patients, the only significant changes observed were decreased fibrinogen and increased protein C. The hemorheological parameters showed a tendency towards normality regardless of whether or not the treatment provided remission of NS. The relationship between hemorheological and hemostatic factors changes are discussed.

The authors studied the global transport of red blood cells (RBC) in a stationary cylindrical tube flow. The human blood was considered as homogeneous fluid. For geometric and dynamic conditions fixed, the quantity of transported RBC was calculated using different models of constitutive equation: i) Newtonian model with apparent viscosity measured at 128 sec-1; ii) Landel's model for rigidified RBC suspension; iii) three non-Newtonian models (Casson law, power law and a relationship of Sisko). We showed that there was an optimum hematocrit for every model for which the quantity of transported RBC was maximum. The values of optimum hematocrit obtained for the non-Newtonian models varied in function of the tube radius and the pressure drop. It was equally observed that the optimum hematocrit was very small when the red blood cells were rigid. These theoretical results merit experimental studies and open the way to investigations of mechanical transport of RBC (global oxygen transport) under different types of flow conditions.

Clinical or pharmacological trials require reproducible laboratory tests. The aim of this work was to investigate the conditions of quality control of two laboratory tests, blood viscosity and red cell aggregation used for hemorheology trials in three centers. The results showed that viscosity measurements require 2 standards. For red cell aggregation, the control suspension standardized media (normal an pathological aggregation) showed a good intercentre reproducibility of the dissociation thresholds but a wide variability of aggregation times. Complementary studies in 5 or 6 centres are planned in order to define national standards of quality control.

Constrained mixture models have been developed in the recent past to describe the mechanical response of blood clots. Most such models capture the formation and dissolution of clots by empirical relations. Here, an attempt is made to capture the variation in rheological material functions with progress of coagulation, within a unified framework for chemically reacting systems. Forms are chosen for the Helmholtz free energy and the rate of entropy production function, such that chemical and mechanical processes that occur during clot evolution are appropriately accounted for. The mechanical response of the clot is assumed to be viscoelastic. The process of clot evolution takes place at a constant physiological temperature which allows for the Helmholtz potential formulation. The model is calibrated and then checked using experimental data (from the literature) for oscillatory shear. A constrained mixture model is presented which accounts for the chemical kinetics of reactions which lead to the formation of clot, and the consequent change in rheological response during coagulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The effects of temperature on micro-rheological variables have not been completely revealed yet. OBJECTIVE: To investigate micro-rheological effects of heat treatment in human, rat, dog, and porcine blood samples. METHODS: Red blood cell (RBC) - buffer suspensions were prepared and immersed in a 37, 40, and 43°C heat-controlled water bath for 10 minutes. Deformability, as well as mechanical stability of RBCs were measured in ektacytometer. These tests were also examined in whole blood samples at various temperatures, gradually between 37 and 45°C in the ektacytometer. RESULTS: RBC deformability significantly worsened in the samples treated at 40 and 43°C, more expressed in human, porcine, rat, and in smaller degree in canine samples. The way of heating (incubation vs. ektacytometer temperation) and the composition of the sample (RBC-PBS suspension or whole blood) resulted in the different magnitude of RBC deformability deterioration. Heating affected RBC membrane (mechanical) stability, showing controversial alterations. CONCLUSION: Significant changes occur in RBC deformability by increasing temperature, showing inter-species differences. The magnitude of alterations is depending on the way of heating and the composition of the sample. The results may contribute to better understanding the micro-rheological deterioration in hyperthermia or fever. [ABSTRACT FROM AUTHOR]

BACKGROUND: Viscosity measurement is challenging due to the internal properties of blood and the artifacts deriving from the various viscometer systems. OBJECTIVE: We aimed to determine the pitfalls of a cone-plate viscometer (Brookfield DV-III Ultra LV) before starting measurements and compare it to our capillary type model (Hemorex Hevimet 40). Effects of sample storage and thermal calibration were assessed as well. METHODS AND RESULTS: Intra-observer variability was studied by 10 replicate measurements of 7 blood samples, mean coefficients of variation were less than 5%. Instruments were compared by measuring 26 blood samples, an average difference of 7% in WBV and 10% in PV was observed. 9 blood samples were stored at 4°C, 22°C and 37°C up to 48 hours to study the effect of storage on viscosity values. WBV at 50 and 100 s-1 became significantly lower after 3 hours at 37°C (p < 0.05). WBV at higher shear rates and PV remained constant at all temperatures. To evaluate the possibility of measuring one sample at different temperatures, 8 blood samples were measured at 40°C with the device calibrated both at 20°C and 40°C; no significant difference was observed. CONCLUSIONS: Thorough validation studies are required before starting experimental and routine viscosity measurements. [ABSTRACT FROM AUTHOR]

BACKGROUND: Isokinetic exercise is used to reduce strength imbalance and to enhance performance. OBJECTIVE: The aim of this study was to investigate the acute effects of a single bout of eccentric isokinetic exercise on hemorheology (erythrocyte deformability and aggregation), total oxidant/antioxidant status (TOS/TAS) and oxidative stress index (OSI) in active individuals. METHODS: The study comprises 11 active, healthy, male subjects (mean age of 19.45 ± 0.31 years, BMI 22.05 ± 0.51 kg/m2). They performed single, unilateral eccentric contractions of knee flexors and extensors with dominant leg on a dynamometer. Isokinetic hamstring, quadriceps strength were recorded at eccentric (30, 120° s−1) angular velocities. Eight active age-matched healthy male subjects were included as a control group, who did not receive exercise. Blood samples were obtained before, immediately after and two days after the exercise session. Hemorheological parameters were measured by an ektacytometer. TOS/TAS were determined using a commercial kit. RESULTS: A session of eccentric isokinetic exercise did not affect erythrocyte deformability and oxidative stress indices, whereas red blood cell (RBC) aggregation was increased initially and returned to pre-exercise levels after two days following exercise. CONCLUSION: Our results suggest that, increased RBC aggregation following an acute bout of isokinetic exercise may result in increased plasma skimming that augments tissue perfusion and clearance of metabolites within a period of two days following exercise. [ABSTRACT FROM AUTHOR]

The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability examined by using laser diffractometry and expressed as elongation index. A significant increase in plasma viscosity at low shear rate and a marked decrease in haematocrit were observed in MM patients compared with normal controls. Also the ratio between the high shear rate whole-blood viscosity and haematocrit ×100 and the ratio between the low and high shear rate plasma viscosity were significantly increased in MM patients. A significant decrease in erythrocyte deformability, especially at low shear stresses, was found. We discuss some hypotheses that might explain the behavior of red blood cell deformability in MM, considering that its impairment, in addition to the increase of plasma viscosity, can alter the microcirculatory flow in these patients. [ABSTRACT FROM AUTHOR]

Background: Age- and gender-related alterations of hemorheological parameters have not been completely elucidated to date. Experiments on older animals may give valuable information on this issue. However, the majority of rheological studies have been performed in young rodents. Objective: We aimed to investigate the influence of aging and gender on hemorheological parameters in rats. Methods: Coeval male ( n = 10 ) and female ( n = 10 ) Wistar (Crl:WI) rats were followed-up over 15 months. Blood samples were obtained from the lateral tail vein at 3, 4, 5, 9, 12, 15 and 18 months of age. Hematological parameters, red blood cell deformability (elongation under shear), osmotic gradient deformability and erythrocyte aggregation were tested. Body weight and the estrus cycle (in females) were also examined. Results: Erythrocyte aggregation showed age- and gender-related variations. Red blood cell deformability was greater in females and gradually decreased over the 15-month period in both genders. Erythrocyte aggregation was greater in male rats at most ages, but did not show consistent changes with age. Conclusions: The micro-rheological parameters showed age-related alterations with gender differences. The effect of the estrous cycle cannot be excluded in female rats. The results provide reference data for studies of aging in rats and of the mechanism related to age and gender differences in hemorheology. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The effect of course administration of amlodipine on whole blood viscosity and on macro- and microrheological parameters was evaluated. MATERIALS AND METHODS: SHRs were treated intragastrically with amlodipine at a dose of 10 mg/kg for 6 weeks. After finishing the course, hemodynamic and hemorheological parameters were measured. RESULTS: The antihypertensive treatment with amlodipine resulted in a significant decrease in mean blood pressure by 29% and left ventricular to body weight mass index by 7%. Nevertheless, BV tended to increase. The administration of amlodipine had no effect on PV, plasma fibrinogen concentration, RBC aggregation, and RBC deformability, but hematocrit was higher (by 6%) than it was in control group. CONCLUSIONS: These results demonstrate that amlodipine has no positive hemorheological improvements when administered to SHRs. [ABSTRACT FROM AUTHOR]

Unsteady pulsatile flow of blood through a porous-saturated, tapered and overlapping stenotic artery in the presence of magnetic field is examined theoretically and computationally. The power law constitutive model is employed to simulate hameo-rheological characteristics. The governing equation is derived assuming the flow to be unsteady, laminar, uni-directional and one-dimensional (1D). A robust, finite difference method is employed for the solution of the governing equation, subject to appropriate boundary conditions. Based on this solution, an extensive quantitative analysis is performed to analyze the effects of blood rheology, body acceleration, magnetohydrodynamic parameter, permeability parameter and arterial geometrical parameters of stenosis on various quantities of interest such as axial velocity, flow rate, resistance impedance and wall shear stress. The computations demonstrate that velocity, flow rate and shear stress increase while resistance to flow decreases with greater permeability parameter. Additionally, the effects of magnetic field are observed to be converse to those of permeability i.e., flow is decelerated and resistance is increased, demonstrating the powerful utility of exploiting magnetic fields in hemodynamic flow control (e.g., intra-corporeal surgical procedures). Furthermore, the size of trapped bolus of fluid is also found to be reduced for large values of the permeability parameter indicating that progressively more porous media circumvent bolus growth. [ABSTRACT FROM AUTHOR]

Elevated blood viscosity is an integral component of vascular shear stress that contributes to the site specificity of atherogenesis, rapid growth of atherosclerotic lesions, and increases their propensity to rupture. Ex vivo measurements of whole blood viscosity (WBV) is a predictor of cardiovascular events in apparently healthy individuals and studies of cardiovascular disease patients. The association of an elevated WBV and incident cardiovascular events remains significant in multivariate models that adjust for major cardiovascular risk factors. These prospective data suggest that measurement of WBV may be valuable as part of routine cardiovascular profiling, thereby potentially useful data for risk stratification and therapeutic interventions. The recent development of a high throughput blood viscometer, which is capable of rapidly performing blood viscosity measurements across 10,000 shear rates using a single blood sample, enables the assessment of blood flow characteristics in different regions of the circulatory system and opens new opportunities for detecting and monitoring cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Red blood cell aggregation at low flow rates increases venous vascular resistance, but the process of aggregate formation in these vessels is not well understood. We previously reported that aggregate formation in postcapillary venules of the rat spinotrapezius muscle mainly occurs in a middle region between 15 and 30 µm downstream from the entrance. In light of the findings in that study, the main purpose of this study was to test two hypotheses by measuring collision frequency along the length of the venules during low flow. We tested the hypothesis that aggregation rarely occurs in the initial 15-urn region of the venule because collision frequency is very low. We found that collision frequency was lower than in other regions, but collision efficiency (the ratio of aggregate formation to collisions) was almost nil in this region, most likely because of entrance effects and time required for aggregation. Radial migration of red blood cells and Dextran 500 had no effect on collision frequency. We also tested the hypothesis that aggregation was reduced in the distal venule region because of the low aggregability of remaining nonaggregated cells. Our findings support this hypothesis, since a simple model based on the ratio of aggregatable to nonaggregatable red blood cells predicts the time course of collision efficiency in this region. Collision efficiency averaged 18% overall but varied from 0 to 52% and was highest in the middle region. We conclude that while collision frequency influences red blood cell aggregate formation in postcapillary venules, collision efficiency is more important. [ABSTRACT FROM AUTHOR]

Separation of red blood cells and plasma in microcirculatory vessels produces a cell-free layer at the wall. This layer may be an important determinant of blood viscosity and wall shear stress in arterioles, where most of the hydraulic pressure loss in the circulatory system occurs and flow regulatory mechanisms are prominent. With the use of a newly developed method, the width of the cell-free layer was rapidly and repeatedly determined in arterioles (10- to 50-µm inner diameter) in the rat cremaster muscle at normal arterial pressure. The temporal variation of the cell-free layer width was non-Gaussian, but calculated mean and median values differed by <0.2 µm. The correlation length of the temporal variations downstream (an indication of mixing) was ~30 µm and was independent of pseudoshear rate (ratio of mean velocity to vessel diameter) and of vessel diameter. The cell-free layer width was significantly different on opposite sides of the vessel and inversely related. Increasing red blood cell aggregability reduced this inverse relation but had no effect on correlation length. In the diameter range studied, the mean width of the cell-free layer increased from 0.8 to 3.1 µm and temporal variations increased from 30% to 70% of the mean width. Increased aggregability did not alter either relationship. In summary, the cell-free layer width in arterioles is diameter dependent and shows substantial non-Gaussian temporal variations. The temporal variations increase as diameter increases and are inversely related on opposite sides of the vessel. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to elucidate the underlying mechanisms responsible for hemorheological abnormalities in elderly patients with Alzheimer's disease (AD). Subjects and Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Free oscillation rheometry (FOR) using the ReoRox® 4 instrument makes it possible, at bedside, to study the coagulation process in blood over time and gives information on clotting time and coagulum elastic properties. In order to find out how various factors influence the FOR analysis we studied the coagulation process and change of elasticity over time in non-anticoagulated and citrated blood samples, plasma samples with various platelet concentrations (0–200 × 109/l) and blood samples with various haematocrit (0–40%). Blood samples supplemented with fibrinogen were analysed to elucidate the importance of fibrinogen on elasticity. The importance of the GPIIb/IIIa receptor on platelets was investigated by comparing the elasticity development in blood samples in presence and absence of a GPIIb/IIIa receptor inhibitor, abciximab. Anticoagulation with citrate did not have major influence on the viscoelastic properties of the coagulum. Increasing number of platelets and increasing fibrinogen concentration resulted in higher elasticity while increasing haematocrit gave lower elasticity. Blood samples with GPIIb/IIIa receptor inhibitor had very low elasticity indicating the importance of functional GPIIb/IIIa receptors. In conclusion we consider FOR to be a useful method to study the elastic properties of the coagulum. Various factors such as the number of red blood cells and platelets as well as the fibrinogen concentration should be taken into consideration when evaluating the results. The ReoRox® 4 instrument had excellent measuring range and unusually small artefactual effects on clot elasticity induced by the instrument in comparison with published results on other instruments. [ABSTRACT FROM AUTHOR]

We studied effects of mental stress on whole-blood viscosity (WBV) and blood pressure (BP), and relations between WBV and autonomic nervous system activity and insulin sensitivity. We measured WBV (rotational rheometer), plasma noradrenaline (NA), finger BP, heart rate variability (HRV) and baroreflex sensitivity (BRS; transfer technique) during hyperinsulinaemic glucose clamp and mental arithmetic stress test (MST) in 20 men with high (?140/90 mmHg) and 21 men with normal (?115/75 mmHg) screening BP, and 10 women regardless of screening BP (all normotensive). WBV and NA increased during the MST, while HRV and BRS decreased. During the MST, WBV (all shear rates) and the response ( ? WBV) (low shear) were higher in men with high compared to normal screening BP ( p <0.05). In men, WBV correlated positively with NA and negatively with HRV, BRS and insulin sensitivity. The diastolic BP response ( ? DBP) was independently explained by high-shear ? WBV ( p <0.05) and ? NA ( p <0.0001), and ? WBV independently by ? DBP ( p <0.05). WBV is related to increased sympathetic activity, impaired vagal cardiac control and low insulin sensitivity in young adults. The haemorheological effect of mental stress is increased in young men with high screening BP and may be mediated by the acute increase in BP. [ABSTRACT FROM AUTHOR]

We studied how the rheological properties of blood influenced capture and rolling adhesion of leukocytes as well as their margination in the bloodstream. When citrated, fluorescently labeled blood was perfused through glass capillaries coated with P-selectin, leukocytes formed numerous rolling attachments. The number of attached leukocytes increased as the hematocrit was increased between 10% and 30% and was essentially constant from 30% to 50%. In EDTA-treated blood, adhesion was absent, and the flux of marginated cells varied little with increasing hematocrit. However, the velocity of marginated leukocytes increased monotonically, whereas the volumetric flow rate was constant, implying that the flow velocity profile became blunted and wall shear rate increased. Thus increasing hematocrit promoted attachment for a given total flow rate, without increasing margination, even though wall shear rate and blood viscosity increased. Blood was diluted to 20% hematocrit with plasma, 40-kDa dextran (to reduce red blood cell aggregation), or 500-kDa dextran (to enhance aggregation). Increasing aggregation correlated with increasing leukocyte adhesion and with more slow-flowing leukocytes near the wall. Thus flowing erythrocytes promote leukocyte adhesion, either by causing margination of leukocytes or by initiating and stabilizing attachments that follow. [ABSTRACT FROM AUTHOR]

Objectives: Lipid emulsions are commonly used for nutrition in critically ill patients. In these patients interventions resulting in deteriorated blood rheology and thereby an impaired microcirculation may be deleterious. This study examined the acute hemorrheological effects of the lipid emulsion Intralipid. We have recently shown that hyperinsulinemia exerts a negative effect on erythrocyte deformability, and here the effect of hyperinsulinemia combined with Intralipid was studied.Subjects and Interventions: Eleven healthy subjects received Intralipid (200 mg/ml) intravenously as a bolus injection (0.5 ml/kg) over 10 min and thereafter as a continuous intravenous infusion (90 ml/h) for 4 h combined with heparin (200 U/h) to stimulate lipolysis. During the final 2 h an euglycemic hyperinsulinemic clamp was added. Five subjects underwent the same protocol with the exception that saline was given instead of Intralipid and heparin.Measurements and Results: Whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured by rotational viscometry. Compared with basal and control values the Intralipid infusion caused greater erythrocyte fluidity (p < 0.05) and less aggregation tendency (p < 0.05). Whole blood and plasma viscosity remained unchanged. Hyperinsulinemia had no significant effect on the hemorrheological variables measured.Conclusions: Intralipid has no deleterious effects on blood rheology in healthy subjects. Instead, it leads to improved erythrocyte aggregation tendency and fluidity. If the emulsion exerts the same effects in patients with impaired circulation, the use of Intralipid may be beneficial in these patients. [ABSTRACT FROM AUTHOR]

Effects of picotamide on platelet activity and on some hemorheologic, coagulative, and hemodynamic parameters were investigated in a randomized, double-blind, placebo-controlled study for eighteen months. Twenty patients, average age 61.5±9.6 (SD) years, with peripheral arterial disease (PAD) at functional stage 2 of the Fontaine classification and with intermittent claudication for at least six months were studied. Ten patients received tablets of picotamide, 300 mg three times a day, and 10 subjects received three identical placebo tablets each day. Similar atherosclerotic disease risk factors were present in both groups. Picotamide induced a significant decrease of plasma viscosity, fibrinogen, and beta-thromboglobulin and an increase of amplitude of the photoplethysmographic wave. [ABSTRACT FROM AUTHOR]

The prevention of cardiovascular disease has up till now generally been limited to control of the classical risk factors. The primary problem of the risk factor model is, that although a statistically verified relationship exists between risk factors and vascular disease, an individual prognosis is presently impossible. Surveys that show a relation between risk factors and impaired blood fluidity support the conception that a change in blood fluidity could be considered an early detection screening of vascular diseases. Prospective studies have shown that the hematocrit is related to circulatory disturbances. The main aim of the present study was to determine the clinical relevance of rheological parameters (hematocrit, plasma viscosity, erythrocyte rigidity, thrombocyte aggregation, erythrocyte aggregation), and the importance of altered blood fluidity as a predictor of manifest cerebral, cardiac or peripheral vascular disturbance. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about granulocyte rheology befoe and after chemotactic activation in deep venous thrombosis.