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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.

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.

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.