Biorheology - Volume 38, issue 2-3

Authors: Schmid‐Schönbein, Geert W. | Kistler, Erik B. | Hugli, Tony E.

Article Type: Research Article

Abstract: Activation of cells in the vascular compartment causes profound alteration of cell rheological properties with impairment of the microcirculation and initiation of inflammatory reactions. Many cardiovascular diseases have been shown to be associated with cell activation and inflammation. While this situation offers the opportunity for new interventions against the deleterious effects of cell activation, there is the need for a better understanding of the mechanisms that lead to cell activation in the first place. We review here several mechanisms for cell activation in the circulation. We show that in shock, a condition associated with severe forms of cell activation, humoral …cell activation factors can be detected in plasma. Further analysis indicates that the source of these humoral activators may be due to the action of pancreatic digestive enzymes in the intestine. Ischemia may serve to open the intestinal brush border and permit entry of pancreatic enzymes into the wall of the intestine to initiate self digestion. In this process low molecular weight but potent cell activators are produced which may escape via the intestinal circulation and the lymphatics into the general circulation. Inhibition of pancreatic enzymes in the lumen of the intestine leads to complete attenuation of humoral activator production as well as many of the deleterious sequelae that accompany shock, such as inflammation and multi‐organ failure. We outline a method to carry out biochemical isolation of the cell activators derived from pancreatic enzymes. This analysis shows that there are multiple species of cell activators above and beyond currently known species, many of which have molecular weights below 3000 Da. Identification of the mechanisms that lead to cell activation is an important part to understand the mechanisms that lead to alterations of rheological properties of blood cells in disease and dysfunction of the endothelium and parenchymal cells. Our current evidence suggests that pancreatic digestive enzymes and tissue enzymes may play a central role in humoral activator production. Show more

Keywords: Endothelium, leukocytes, actin polymerization, adhesion molecules, pancreatic enzymes, proteases, inflammatory mediators, shock, ischemia, reperfusion, intestine, brush border, extracellular proteins, SepPak elution, platelet activating factor, leukotriene, peptides

Citation: Biorheology, vol. 38, no. 2-3, pp. 185-201, 2001

Authors: Reinhart, Walter H.

Article Type: Research Article

Abstract: Blood viscosity is determined by plasma viscosity, hematocrit, erythrocyte deformability and aggregation. Plasma viscosity and hematocrit are directly regulated by the organism. The molecular biology of the principal determinants of plasma viscosity, i.e., fibrinogen, immunoglobulins, albumin, and lipoproteins is outlined in this work. Hematocrit is regulated by erythropoietin, which is primarily induced by tissue hypoxia. Evidence begins to emerge that autoregulatory mechanisms may be involved in blood viscosity. Viscosity modulates gene transcription for albumin and apolipoproteins in cultured hepatocytes and the erythropoietin response to anemia in rats. Further investigations into these self‐regulatory mechanisms in biorheology are, however, needed for a …better understanding of blood viscosity regulation in health and disease. Show more

Keywords: Albumin, erythropoietin, fibrinogen, gammaglobulin, lipoprotein, molecular biology, viscosity

Citation: Biorheology, vol. 38, no. 2-3, pp. 203-212, 2001

Authors: Skilbeck, Christopher | Westwood, Susan M. | Walker, Peter G. | David, Tim | Nash, Gerard B.

Article Type: Research Article

Abstract: We have recently described patterns of adhesion of different types of leukocytes downstream of a backward facing step. Here the predicted fluid dynamics in channels incorporating backward facing steps are described, and related to the measured velocities of flowing cells, patterns of attachment and characteristics of rolling adhesion for neutrophils perfused over P‐selectin. Deeper (upstream depth 300 μm, downstream depth 600 μm, maximum wall shear stress ∼0.1 Pa) and shallower (upstream depth 260 μm, downstream depth 450 μm, maximum wall shear stress ∼0.3 Pa) channels were compared. Computational fluid dynamics (CFD) predicted the presence of vortices downstream of the steps, …distances to reattachment of flow, local wall shear stresses and components of velocity parallel and perpendicular to the wall. Measurements of velocities of perfused neutrophils agreed well with predictions, and suggested that adhesion to P‐selectin should be possible in the regions of recirculating flow, but not downstream in re‐established flow in the high shear channel. When channels were coated with a P‐selectin–Fc chimaera, neutrophils were captured from flow and immobilised. Capture showed local maxima around the reattachment points, but was absent elsewhere in the high shear chamber. In the low shear chamber there was depression of adhesion just beyond the reattachment point because of expansion of flow and depeletion of neutrophils near the wall. Inside the recirculation zones, adhesion decreased approaching the step because of an increasing, vertically upward velocity component. When channels were coated with P‐selectin, neutrophils rolled in all regions, but lifted off the surface as they rolled backwards into low shear regions near the step. Rolling velocity in the recirculation zone was independent of shear stress, possibly because of the effects of vertical lift. We conclude that while local wall shear stress influences adhesive behavior, delivery of cells to the wall and their behavior after capture also depend on components of flow perpendicular to the wall. Show more

Citation: Biorheology, vol. 38, no. 2-3, pp. 213-227, 2001

Authors: Tsai, Amy G. | Intaglietta, Marcos

Article Type: Research Article

Abstract: Hemorheological studies lead to the axiom that high plasma viscosity is detrimental and that it is beneficial to lower blood viscosity, a precept embodied in the practice of hemodilution, where improved perfusion is attributed to the lowering of blood viscosity. Hemodilution is limited by the transfusion trigger, hemoglobin content of blood of about 7–8 g/dl, which indicates when further volume replacements must restore oxygen carrying capacity with red blood cells (RBC). However, oxygen consumption and delivery are not compromised upon passing this landmark. The reduced blood viscosity does not transmit adequate pressure to the capillaries, causing functional capillary density (FCD) …to decrease, jeopardizing organ function through the inadequate extraction of products of metabolism from the tissue by the capillaries. Studies in hemorrhagic shock show that survival is primarily determined by the maintenance of FCD and secondarily by tissue oxygenation. FCD is maintained as hematocrit is reduced beyond the transfusion trigger by increasing plasma viscosity, which transmits systemic pressure to the capillaries and induces vasodilatation through the increased shear stress dependent release of vasodilators. Consequently the transfusion trigger is also a “viscosity trigger” indicating when blood and plasma viscosity are too low. In this condition increasing plasma viscosity is beneficial and extends the transfusion trigger reducing the use of blood transfusions. Show more

Keywords: Plasma viscosity, transfusion trigger, functional capillary density, hemodilution, high molecular weight dextrans, tissue survival, oxygen delivery

Citation: Biorheology, vol. 38, no. 2-3, pp. 229-237, 2001

Authors: Armstrong, Jonathan K. | Meiselman, Herbert J. | Wenby, Rosalinda B. | Fisher, Timothy C.

Article Type: Research Article

Abstract: Despite many years of research, the physiologic or possible pathologic significance of RBC aggregation remains to be clearly determined. As a new approach to address an old question, we have recently developed a technique to vary the aggregation tendency of RBCs in a predictable and reproducible fashion by the covalent attachment of nonionic polymers to the RBC membrane. A reactive derivative of each polymer of interest is prepared by substitution of the terminal hydroxyl group with a reactive moiety, dichlorotriazine (DT), which covalently bonds the polymer molecule to membrane proteins. Pluronics are block copolymers of particular interest as these copolymers …can enhance or inhibit RBC aggregation. Pluronics exhibit a critical micellization temperature (CMT): a phase transition from predominantly single, fully hydrated copolymer chains to micelle‐like structures. The CMT is a function of both copolymer molecular mass and concentration. This micellization property of Pluronics has been utilized to enhance or inhibit RBC aggregation and hence to vary low‐shear blood viscosity. Pluronic‐coated RBCs were prepared using reactive DT derivatives of a range of Pluronics (F68, F88, F98 and F108) and resuspended in autologous plasma at 40% hematocrit. Blood viscosity was measured at a range of shear rates (0.1–94.5 s−1 ) and at 25 and 37°C using a Contraves LS‐30 couette low shear viscometer. RBC aggregation and whole blood viscosity was modified in a predictable manner depending upon the CMT of the attached Pluronic and the measurement temperature: below the CMT, RBC aggregation was diminished; above the CMT it was enhanced. This technique provides a novel tool to probe some basic research questions. While certainly of value for in vitro mechanistic studies, perhaps the most interesting application may be for in vivo studies: typically, intravital experiments designed to examine the role of RBC aggregation in microvascular flow require perturbation of the suspending plasma to promote or reduce aggregation (e.g., by the addition of dextran). By binding specific Pluronics to the surface, we can produce RBCs that intrinsically have any desired degree of increased or decreased aggregation when suspended in normal plasma, thereby eliminating many potential artifacts for in vivo studies. The copolymer coating technique is simple and reproducible, and we believe it will prove to be a useful tool to help address some of the longstanding questions in the field of hemorheology. Show more

Keywords: Red blood cell, aggregation, Pluronic, poloxamer, micellization, covalent

Citation: Biorheology, vol. 38, no. 2-3, pp. 239-247, 2001

Authors: Lerche, Dietmar | Frömer, Dirk

Article Type: Research Article

Abstract: The flow properties of blood are mostly determined using various viscometric approaches, and described in terms of a shear rate or shear stress dependent apparent viscosity. The interpretation of results are rather difficult, especially at low shear rates when particle sedimentation and migration within the viscometer gap are significant. By contrast, analysing the separation process in concentrated RBC suspensions in a centrifugal field also yields information about the viscosity function, including particle–particle interaction and deformation parameters. In this paper, the sedimentation process is approached by means of the theory of kinematic waves and theoretically described by solving the corresponding one‐dimensional …quasi‐linear partial differential equation based on viscosity/flow function as a function of volume concentration. The sedimentation kinetics of rigid spherical RBC suspended in saline and normal RBC suspended in Dx‐saline solutions were investigated by means of a separation analyser (LUMiFuge 114). The instrument detects the light transmission over the total length of the cell containing the suspension. During centrifugation the analyser automatically determines the position of the particle free fluid/suspension interface or the sediment by mans of a special algorithm. The data obtained with sedimentation of rigid spherical RBC at different volume concentrations demonstrate that, in the case of suspensions rotated in containers of constant cross section, there is good agreement between the theory of kinematic waves developed by Anestis and Schneider (1983) and the results of the experiments. Such good agreement was obtained even though a restrictive one‐dimensional model was used to obtain the theoretically derived sedimentation time course. In addition, we describe an algorithm enabling the experimental determination of the viscosity and related flux density function to be made for any suspension. Through this approach, we investigated in detail the rheological behavior of suspended rigid spheres at low Reynolds numbers ranging from 10−6 to 10−3 . The method here introduced also enabled us to investigate RBC suspensions with respect to the deformability and interactions of the cells by means of the separation analysis. Normal, rigid as well as aggregating RBC exhibited marked differences in the sedimentation kinetics, which were quantified by means of the flux and viscosity functions based on the theory of kinematic waves. Show more

Keywords: Dispersion, sedimentation kinetics, particle interaction, deformation, viscosity, LUMiFuge

Citation: Biorheology, vol. 38, no. 2-3, pp. 249-262, 2001

Authors: Bishop, Jeffrey J. | Popel, Aleksander S. | Intaglietta, Marcos | Johnson, Paul C.

Article Type: Research Article

Abstract: It has long been recognized that understanding the rheological properties of blood is essential to a full understanding of the function of the circulatory system. Given the difficulty of obtaining carefully controlled measurements in vivo, most of our current concepts of the flow behavior of blood in vivo are based on its properties in vitro. Studies of blood rheology in rotational and tube viscometers have defined the basic properties of blood and pointed to certain features that may be especially significant for understanding in vivo function. At the same time, differences between in vivo and in vitro systems combined with …the complex rheological properties of blood make it difficult to predict in vivo blood rheology from in vitro studies. We have investigated certain flow properties of blood in vivo, using the venular network of skeletal muscle as our model system. In the presence of red blood cell aggregation, venous velocity profiles become blunted from the parabolic as in Poiseuille flow, as pseudo‐shear rate (= mean fluid velocity/vessel diameter) is decreased from ∼100 s−1 to 5 s−1 . At control flow rates, the short distance between venular junctions does not appear to permit significant axial migration and red cell depletion of the peripheral fluid layer before additional red cells and aggregates are infused from a feeding tributary. Formation of a cell‐free plasma layer at the vessel wall and sedimentation in vivo are evident only at very low pseudo‐shear rates (<5 s−1 ). These findings may explain in large part observations in whole organs of increased venous resistance with reduction of blood flow. Show more

Keywords: Red blood cell sedimentation, axial migration, velocity profiles, venous vascular resistance, blood viscosity

Citation: Biorheology, vol. 38, no. 2-3, pp. 263-274, 2001