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Vascular engineering developed through advancing knowledge of the physiological and pathological processes operating in cells and tissues subjected to environmental mechanical stress. We review briefly the more relevant cellular and general mechanism characteristic of vascular tissue examining the performances obtained with prosthetic materials (allografts, synthetic grafts) and current research and development of new vessel substitutes (biohybrids or biovessels).

The adhesion of polymorphonuclear leukocytes (PMNs) on the vascular endothelium is a complex process that occurs during different biological and pathological events and involves numerous molecules. The adhesion cascade is induced after PMN stimulation by various molecular or cellular signals. Fibrinogen is one of the substrates for CD11b/CD18 B2-integrins expressed at the PMN surface; fibrinogen-neutrophil binding is induced by inflammatory reactions. In order to understand this process, we have carried out studies on the basis of preliminary experiments on red blood cells and synthetic particles. The modelization of quiescent PMNs adhesion on a fibrinogen substrate was investigated with a sedimentation cell chamber. Two different physiological conditions were tested: the activated state of PMN by a synthetic pro-inflammatory activator (FMLP). The activated state of PMNs was both quantified by flow cytometry and controlled by fluorescence microscopy. The results suggest that quiescent neutrophils deposit in accordance with the ballistic deposition model. This random adsorption model differs from random sequential adsorption (RSA) in that the cells arriving at the surface are able to roll along cells previously adsorbed introducing the notion of gravitational attraction of cells. The preliminary results obtained with stimulated PMN do not allow to choose between one of this two deposition models. Nevertheless, the qualitative and quantitative effects of FMLP on neutrophils were demonstrated by modifications of adhesion molecules expression.

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 pathogenesis of atheromatous and/or thrombotic vascular diseases involves rheological parameters, soluble mediators and cellular agents. The many studies that have tried to establish correlations between plasma factors, shear stress and the risk of ischemia have left some questions unanswered. Current exploration methods are now focusing on the determining role of cells. Activated cells express adhesion molecules on their membranes, which allow to communicate in a homo- or heterotypical manner. Quantifying adherence molecules on the surface of platelets, leukocytes and endothelial cells provides an assessment of the "adhesive phenotypical profile". Quantitative cytometry, using beads coated with a known amount of immunoglobulins as calibrators, is perfectly suited, through its multiple parameter analyses and the specificity provided by monoclonal antibodies, for the quantification of membrane antigens. Measuring the adhesive profile on the surface of cells that are implicated in vascular disease makes it possible to correlate that phenotype to the ischemic risk in such diversified pathologies or circumstances as intermittent angor, myocardial infarction, angioplasty, insulin-dependent diabetes or pre-eclampsia. In addition, that quantification permits monitoring the action of new therapeutical agents targeting adherence molecules.

As in most living tissues, a network of nutritional vessels, the so-called vasa vasorum, irrigates the vessel wall under physiological conditions. An alteration or obstruction of this network can induce severe lesions. Most normal arteries and veins are irrigated by a vasa vasorum network located mainly in the adventice. They essentially supply oxygen to the outer layers of the vascular wall, the inner layer being mainly oxygenated by direct diffusion from bloodstream. Vasa vasorum responds to vasomotor stimuli and can even regress, e.g., after vascularization of arterial grafts. Their pathophysiological importance for arteries is now established. Indeed, it is known that an infusion disorder or vasa vasorum alteration may induce or promote early atherosclerotic lesions, fibrodysplasia or even media necrosis. From a mechanical point of view, and considering the three layers as a unique material, the vessel shows non-isotropic linear elastic and incompressible (v = 0.5) behaviour in the case of minimal or moderate deformation. But in the case of major deformation, the vessel displays a non-linear behaviour. The interaction between vasa vasorum supply and the mechanical properties of the arterial vascular wall can promote the occurrence of aneurysms as soon as vasa vasorum irrigation decreases. Some authors have hypothesized that these microvessels could fulfil the same function in the venous wall. It appears also that microcirculation flow rates are lower in varicose veins than in healthy ones and that partial oxygen pressure, already low in a healthy vein media, is even lower in a varicose vein. All these facts underline the importance of supply by the vasa vasorum network and its determining role in maintaining vascular wall integrity. In addition, the influence of vessel non-linear properties and their pathological changes on microcirculation would partially explain media necrosis in arteries and veins. Studying vascular wall deformation under the influence of intraluminal pressure revealed that an initially circular vasa vasorum rapidly takes on an elliptical shape which results more from crosswise circumferential stretching of the wall than from radial crushing. This induces increased hydraulic resistance. Thus permanent overpressure reduces vascular wall irrigation. Once the wall has been devascularized, it will loose its elasticity, harden and retain its maximal deformation. A vicious circle is then created. This phenomenon, noticeable in arteries, could be more serious in veins because their walls are thinner and elasticity modulus is lower. For example, for an intraluminal overpressure of 100 mmHg in an artery and 10 mmHg in a vein the ellipticity of the vasa vasorum becomes 1.2 and 3 respectively. Based on the hypothesis of a linear elastic behaviour and a periodical intraluminal overpressure, the ratio of the two axis of an arterial vasa vasorum B/A varies from 1.13 to 1.28 for Pa = 100 + 30 sin (2 pi t) mmHg, and from 1.24 to 1.44 for Pa = 160 + 40 sin (2 pi t) mmHg. In this case, the ratio of hydraulic resistances R(ellipse)/R(circle) changes little (less than 1, the ratio of the axis varies from 1.1 to 2.6 for Pa = 5 + 5 sin (2 pi t) mmHg) and from 1.8 to 5.8 for Pa = 10 + 5 sin (2 pi t) mmHg). Thus the ratio of hydraulic resistance varies from 1 to 1.5 and from 1.2 to 2.8 respectively. In practice Young's modulus increases in parallel with luminal pressure by limiting vascular wall and vasa vasorum deformation. If we consider the non-linear behaviour of the vessel wall and suppose the same conditions of intraluminal pressure, the ratio of the axis of the venous vasa vasorum in a hypertensive patient varies from 1.6 to 2.6 (instead of 1.8 to 5.8 in the case of linear model). This ratio is higher than that of the healthy subject which is less than 1.7. So the vascular structure in physiological conditions itself reacts to the pressure increases which may jeopardize vasa vasorum irrigation by delaying mural transfor

The effect of cholesterol hemisuccinate incorporation on the rheological properties of the erythrocyte membrane was assessed by measuring deformability (elongation index) and osmotic fragility ("baseline hemolysis"). These two experimental methods have different response sensitivities according to the incubation protocols (12 h 25 degrees C/12 h 25 degrees C then 12 h 37 degrees C) ant to the amount of cholesterol incorporated in the membrane (C/Pt from 0.18 to 0.83). The deformability and osmotic fragility variations observed are inversely related with the cholesterol concentrations incorporated. The experimental differences observed in the deformability and osmotic fragility are discussed in view of the type of membrane deformation and of the signals collected by the two systems.

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 authors study the blood flow in a cylindrical vessel with the consideration of the non-newtonian behaviour of blood. Supposing that the vessel's diameter and the blood velocity at the centre are known (measurable by a Doppler ultrasound velocimeter), we calculate the velocity profiles, flow rate, wall shear stress and shear rate, with 8 non-newtonian models, by a numerical method which allows us to solve the flow system for any non-newtonian fluid. The numerical results are compared with those obtained for a newtonian fluid which remains the most used model in clinical practice. This work shows the importance of the use of a realistic non-newtonian rheological relationship in the estimation of mechanical factors especially the wall shear stress in blood circulation.

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.

An in vitro model was designed to examine the effect of three contrast media (CM): two non ionic (Iohexol, Iopamidol) and one ionic (Ioxaglate) molecules on erythrocyte aggregation. Red blood cells were suspended in a chemically defined medium (Albumin: 10 g/l), Immunoglobulins: 12 g/l, Fibrinogen: 1.5 g/l) supplemented with various proportions of CM (10-25% V/V). Control samples contained NaCl or Saccharose solutions with a nearly similar osmolality. Erythrocyte aggregation at constant hematocrit (HT = 40%) was determined by the analysis of the light backscattered by blood suspension during the aggregation process. As compared to control samples, non ionic CM induced a weak decrease in erythrocyte aggregation, when the ionic molecule caused a marked increase in the aggregation, which was related to CM concentration. A different interaction of ionic and non ionic CM with erythrocyte membranes has been shown by fluorescence studies. After addition of CM, it was noted a fluorescence quenching of lipophilic probes (TMA-DPH and DPH) embedded in erythrocyte membranes. This quenching probably due to benzene ring and iodine atoms of contrast media markedly varied according to the used fluorescent probe and the CM. In the presence of ionic CM, the fluorescence quenching is more important than that induced by non ionic CM. Thus, besides osmolality and viscosity of CM which play a role in erythrocyte aggregation, some intrinsic properties of CM such as the ionic or non ionic nature could influence erythrocyte membrane-contrast medium interactions and consequently erythrocyte aggregation.

The objective was to investigate in vivo the rheological effects of plasma substitutes (fluid gelatin, dextran 40, dextran 60, hydroxyethylstarch). The study was performed during a hypervolemic hemodilution in 60 adult volunteers who underwent an odontological surgery. Two control groups were infused with Ringer-Lactate or 4% human albumin. Each patient was infused with 500 ml of plasma substitute or control fluid. Blood samples were obtained at four different times: prior to (t0) and immediately after (t1) the infusion, then 3 hours (t2) and 24 hours (t3) after the hemodilution. At t1 and t2, plasma viscosity did not present important variations, except for the group infused with dextran 60 where a significant increase in plasma viscosity was observed. Blood viscosity and erythrocyte aggregation measurements were performed at hematocrit 40% to determine the intrinsic properties of substitute and eliminate the effects of hemodilution. Blood viscosity at high shear rates underwent minor variations in all groups. In contrast, blood viscosity at low shear rate and aggregation parameters exhibited important variations which markedly depended on the used substitute. The infusion of Ringer-Lactate, albumin and dextran 40 induced a significant decrease in blood viscosity and in erythrocyte aggregation. With dextran 60 and gelatin, blood viscosity and erythrocyte aggregation increased. Finally, the infusion with hydroxyethylstarch did not present important differences as compared to the results recorded at t0. Twenty for hours after the infusion, it should be noted an increase in plasma fibrinogen, probably due to surgery, which caused an increase in erythrocyte aggregation in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Analyses of erythrocyte aggregation have been carried out in 15 patients with multiple myeloma or Waldenström's macroglobulinemia before and after plasma exchange. The volume of exchanged plasma was about 1.2-1.5 plasmatic mass. It was replaced by the same volume of a 4% solution of human albumin. Each treatment included at least 3 plasma exchanges at 48 hours intervals. The kinetic (aggregation times) and rheological (dissociation threshold) parameters of erythrocyte aggregation were determined before and immediately after each plasma exchange using a device based on the analysis of the backscattered light by a blood suspension. Before the first plasma exchange, erythrocyte aggregation measurements revealed a pronounced reduction in time aggregation and high values of dissociation thresholds indicating an hyperaggregation of red cells. The successive plasma exchanges produced very different changes in erythrocyte aggregation. For some patients, the aggregation parameters presented normal values from the first plasma exchange when similar changes were only noted after the second plasma exchange in other patients. Finally, in some cases, an hyperaggregation state was maintained after a series of three plasma exchanges. The influence of the nature and the concentration of monoclonal immunoglobulin as well as plasmatic fibrinogen are discussed.

Although the non-Newtonian characteristics of blood have now been accurately defined, the influence and effect of a hyperviscosity syndrome at the onset of ischemia and in oxygen transport to the tissues remains within the realm of assumptions. Using a simple theoretical approach it can be shown that oxygen transport capacity to the tissues is proportional to the radio H/eta s (where H = hematocrit, eta s = blood viscosity), as long as vascular bed geometry remains constant (with no sign of compensatory vasodilation). With the help of examples, the authors show the changes in oxygen transport as a function of various rheological parameters (red cell aggregation ans deformability). Further, the authors introduce the concept of a hemorheological profile for taking all the hemorheological parameters into consideration and for standardising the presentation of the results for hyperviscosity syndromes.

Translational motions of lipids and proteins and molecular motions within the lipid hydrocarbon chains of biological membranes can be approached by spectroscopic methods. The electron spin resonance (ESR) spectra of spin labels bound on proteins or grafted on fatty acids and incorporated into biological membranes undergo characteristic changes which may be resolved in terms of modifications of membrane environment. However, the method is still scarcely used in routine clinical studies. In contrast, fluorescence methods such as intermolecular excimers or fluorescence polarization might join the ranks of routine analyses. The labeling of lipid compartments with fluorescent probes and the study of their spectroscopic properties give informations on the cohesion of their immediate environment. Polyenic molecules (DPH and TMA-DPH) which are located in different lipid compartments characterize deep and superficial areas of cell membrane, respectively. A set of probes in which a 9-anthroyloxy group is attached to different positions of a long chain fatty acid provides a means of measuring a fluidity gradient into membrane bilayer. Thus, these fluorescence methods which are simple and rapid represent a semi-quantitative approach of the so called "membrane fluidity". Modifications in membrane fluidity can control the expression of proteins, receptors exposed on cell surface and alter functional properties of cells. Moreover, pathological processes can also be related to fluidity modifications. In particular, in hypertension and vascular diseases, a decrease in membrane fluidity has been shown in platelets and red cells. Nevertheless, further investigations combining biophysical, biochemical and immunological methods are needed to determine the exact relations between membrane fluidity, classical rheological properties and cell functions.

Hemorheological parameters must be taken into account for a better knowledge of venous flow properties. The postcapillary venules are the region of lowest shear rates and therefore the region of highest whole blood viscosity. Red cell aggregation plays a major role in blood viscosity, especially at low shear rate. This microrheological parameter can be increased in pathological circumstances, including a low capillary flow, venular insufficiency, elevated hematocrit, high levels of acute phase proteins. At the level of the capillaries, microcirculatory stasis leads to a low oxygen supply and consequently to poor metabolic state lowering local ATP levels. As a result, both platelet and white blood cell functions are compromised. Hemorheological studies have shown that both deep venous thrombosis and chronic venous insufficiency are associated with high blood viscosity mainly due to an increased red cell aggregation. This hemorheological vicious circle--stasis promoting hyperviscosity leading to further stasis--could be broken up by therapeutic intervention including hemodilution, fibrinolytic drugs or other specific agents.

Various hemorheological parameters were studied in venous blood samples taken during the initial stages of acute medical emergencies in patients admitted to the Intensive Care Unit. These included more particularly: cerebrovascular accidents, recent acute arterial or venous thrombosis, pulmonary embolism, acute renal failure, pregnancy toxemia and emergencies occurring during pregnancy or in the puerperium, coagulation disorders, gas embolism... The examinations conducted were:--measurement of apparent--blood viscosity (eta a) and plasma viscosity--platelet aggregate fixation after fixing in formalin according to the method described by Wu and Hoak--blood filterability through filters with pores 5 microns in diameter. The principal modifications observed, often correlated were raised blood and plasma viscosity, reduction in the aggregation index, and diminution in filterability. It should be noted that the increase in viscosity, constant in all groups, is significant at low shearing speeds in the thrombosis cases, and that this significance is present in nearly all the pathological groups with high shearing speeds. Variations in the aggregation index are very dispersed and of low significance.

The part played by blood rheological factors in any vasomotor phenomenon is still difficult to define, in relation to its onset, maintenance and possible worsening. A high viscosity may contribute towards a difficulty in flow and viscosity is known to vary in an inverse manner with temperature. Many studies have been published reporting results of rheological investigations in Raynaud's syndromes, but whereas the majority describe both blood and plasma hyperviscosity, others report negative results or those that are interpretable with difficulty. A recent study in 49 patients with Raynaud's syndromes confirmed the presence of elevated blood and plasma viscosity values, particularly in Raynaud's syndromes secondary to other disorders and in digital arteritis. Elevated viscosity levels in "essential" Raynaud's syndromes were significant at low speeds only, suggesting the association of a disorder of erythrocyte aggregation with the properly termed vasomotor disturbance.

16 arteritic patients at stages II, III or IV according to Fontaine's ranking system were treated by normovolemic hemodilution (HDN). The procedure consisted of the daily withdrawal of 500 ml of blood, which was replaced by 250 ml of a 4% solution of human albumin and 250 ml of Dextran 40. The procedure was applied, on average, for three days in succession until the patient's hematocrit reached 0.30. The therapy was carried out over a total of 8 weeks in order to maintain hematocrit levels at between 0.30 and 0.35. Improvement was observed in clinical factors: a 100% increase in walking perimeter in stage II patients, disappearance of decubitus pain in stage III patients, wound healings in stage IV patients. The following rheological and platelet parameters were studied: plasma and blood viscosity with hematocrit level 0.40 and for seven speed of scissoring, red blood cell aggregation index, platelet aggregation, MDA platelet levels, plasma BTG. Clinical results revealed that by the 56th day of treatment, 8 patients had improved and 8 remained stationary (the condition of 3 of the "stationary" patients in fact worsened having evolved according to the normal development of arteritic disease). The improvements observed persist several months after normovolemic hemodilution has been discontinued, with the results for the longest studied patient going back as far as 15 months. With regard to the hemorheological parameters (which, on Day 0, are always disturbed), they tend to improve during the hospitalization period and stabilize at levels lying between the values measured on Day 0 and normal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Incorporation in vitro of 1,6-diphenyl-1,3,5 hexatriene (DPH) in washed human blood platelets was studied to determine a reference value of fluorescence emission anisotropy of DPH and thus the "microfluidity " of platelet lipid zones. Parameters evaluated were the effect of time of incorporation of the marker, of temperature (25 and 37 degrees C), and of cellular concentration, as well as the effect of platelet aging, enabling determination of valid experimental conditions for studying interaction with drug molecules.

A Couette type coaxial cylinder viscosimeter was used to evaluate the influence of deformation rates up to 20,000/s on blood platelets, in the presence or absence of red cells. Plasma lactate dehydrogenase and haemoglobin levels were determined in order to assess cell lysis and the estimation of beta-thromboglobulin (beta-TG) was considered to be an index of platelet activation. Results for whole blood revealed a change in red cells from 10,000/s upwards, which increased as the rate rose. At the same time, beta-TG rose slowly from the lowest deformation rates then considerably, in relation with the liberation of erythrocytic substances. The rise in LDH and beta-TG levels in platelet rich plasma (PRP) remained small up to 7,000/s approximately, then increased very rapidly, suggesting earlier mechanical and biochemical activation than in whole blood.

The microcirculation constitutes an ubiquitous vascular network presenting a mesh pattern, and comprising different types of vessels, arterioles, small veins, capillaries, arteriovenous shunts or similar structures, and lymphatics. Many dimensions have to be recognized, or simply mentioned, if one is to understand the hemodynamic and hemorheological particulars of this territory, which differ, in many aspects, from those specific to the macrocirculation (number and length of the vessels, diameter and cross section, intercapillary distance, geometric characteristics, intravascular pressure, pressure gradient, pressure-volume relationship, flow rate, mean velocity of plasma and RBC, velocity profile, local hematocrit, in situ viscosity, kinematic viscosity, wall shearing conditions, local oxygen transport, aggregation and deformability of RBC, leukocyte properties, etc.). The flow rate in capillary tubes and capillary vessels of the living organism varies with many factors, such as proximal hemodynamics, hemorheological characteristics of blood (fibrinogen, macro- and micro-hematocrit), some known effects (Farheus, Farheus Lindqvist), local diameter, the plasma layer which plays the role of the limiting layer, the endothelial film, the wall effect, and so forth. Models of the circulation have been propounded, none of which takes into account the whole of these phenomena due to their great complexity. Hemodynamic and hemorheological interactions provide for a better understanding of certain concepts, such as vascular resistance, hindrance, capacitance, local flow rates, real capillary opening and closing, development of two-directional functional shunts, autoregulation, pressure-volume relationship, critical closing pressure, circulatory current slowing effect, sequelae of intravascular aggregation of formed blood elements.