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Biomedical subjects

T W Secomb

Publications and source records attributed to T W Secomb.

At least 73 records · Page 4Linked to original sources
PubMed1990

Blood flow in microvascular networks. Experiments and simulation.

A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter.

Animals↗
PubMed1989

A Green's function method for analysis of oxygen delivery to tissue by microvascular networks.

A theoretical model is formulated for analyzing oxygen delivery from an arbitrary network configuration of cylindrical microvessels to a finite region of tissue. In contrast to models based on the classical Krogh cylinder approach, this model requires no a priori assumptions concerning the extent of the tissue region supplied with oxygen by each vessel segment. Steady-state conditions are assumed, and oxygen consumption in the tissue is assumed to be uniform. The nonlinear dissociation characteristics of oxyhemoglobin are taken into account. A computationally efficient Green's function approach is used, in which the tissue oxygen field is expressed in terms of the distribution of source strengths along each segment. The utility of the model is illustrated by analyses of oxygen delivery to a cuboidal tissue region by a single segment and by a six-segment network. It is found that the fractional contribution of the proximal segments to total oxygen delivery increases with decreasing flow rate and metabolic rate.

Animals↗
PubMed1989

Morphologic and hemodynamic comparison of tumor and healing normal tissue microvasculature.

The purpose of this study was to compare microvascular morphometric and hemodynamic characteristics of a tumor and granulating normal tissue to develop quantitative data that could be used to predict microvascular characteristics which would be most likely associated with hypoxia. The dorsal flap window chamber of the Fisher 344 rat was used to visualize the microvasculature of 10 granulating and 12 tumor (R3230 AC adenocarcinoma) tissues at 2 weeks following surgical implantation of the chamber. Morphometric measurements were made from photomontages and video techniques were used to assess red cell velocities in individual vessels. The percent vascular volume of both tissues was close to 20%, but significant differences were noted in other morphometric and hemodynamic measurements. Individual vessel dimensions (length and diameter) in tumors averaged twice as large as those in granulating tissues. Furthermore, red cell velocities were twice as high in tumors as in granulating tissues. In addition to these large differences in average values, there was significant heterogeneity in tumor microvascular morphometry, indicating spatial nonuniformity compared with the granulating tissue. Approximations of vessel spacing, indicated an average of 257 and 118 microns in tumors and granulating tissues, respectively. Vessel densities were four times greater in granulating tissues than in tumor tissues. These results indicated that intervessel distances were more likely to result in hypoxia in tumors, especially considering the wide variability in that tissue. Analysis of flow branching patterns showed that vascular shunts occurred frequently in vessels ranging from 10 to 90 microns in diameter. The results of this study indicate, in this tumor model, that conditions such as low vascular density, vascular shunts, excessive vascular length and/or low red cell velocity exist to a greater extent than the granulating tissue control. These conditions are likely to be conductive to the development of hypoxia.

Adenocarcinoma↗
PubMed1989

Motion of nonaxisymmetric red blood cells in cylindrical capillaries.

We analyze theoretically the single-file flow of asymmetric red blood cells along cylindrical capillaries. Red cells in narrow capillaries are typically nonaxisymmetric, with the cell membrane moving continuously around the cell. In our analysis, cell shape and streamlines of membrane motion are prescribed. Lubrication theory is used to compute velocities and pressures in the fluid surrounding the cell. Conditions of zero lift, zero torque, zero drag, and energy conservation in the cell are imposed. Predicted tank-treading frequency, cell inclination and transverse displacement are small. Cell asymmetry and tank-treading are found to have little effect on the apparent viscosity of blood in capillaries with diameters up to 7 microns.

Blood Flow Velocity↗
PubMed1989

Effects of aggregation on the flow properties of red blood cell suspensions in narrow vertical tubes.

The flow properties of aggregating red cell suspensions flowing at low rates through vertical tubes with diameters from 30 microns to 150 microns are analyzed using a theoretical model. Unidirectional flow is assumed, and the distributions of velocity and red cell concentration are assumed to be axisymmetric. A three-layer approximation is used for the distribution of red cells, with a cylindrical central core of aggregated red cells moving with uniform velocity, a cell-free marginal layer near the tube wall, and an annular region located between the core and the marginal layer containing suspended non-aggregating red cells. This suspension is assumed to behave approximately as a Newtonian fluid whose viscosity increases exponentially with red cell concentration. Physical arguments concerning the mechanics of red cell attachment to, and detachment from the aggregated core lead to a kinetic equation for core formation. From this kinetic equation and the equation for conservation of red cell volume flux, a relationship between core radius and pressure gradient is obtained. Then the relative viscosity is calculated as a function of pseudo-shear rate. At low flow rates, it is shown that the relative viscosity decreases with decreasing flow and that the dependence of relative viscosity on shear rates is more pronounced in larger tubes. It is also found that the relative viscosity decreases with increasing aggregation tendency of suspension. These theoretical predictions are in good qualitative and quantitative agreement with experimental results.

Blood Viscosity↗
PubMed1988

Interaction between bending and tension forces in bilayer membranes.

A theoretical analysis is presented of the bending mechanics of a membrane consisting of two tightly-coupled leaflets, each of which shears and bends readily but strongly resists area changes. Structures of this type have been proposed to model biological membranes such as red blood cell membrane. It is shown that when such a membrane is bent, anisotropic components of resultant membrane tension (shear stresses) are induced, even when the tension in each leaflet is isotropic. The induced shear stresses increase as the square of the membrane curvature, and become significant for moderate curvatures (when the radius of curvature is much larger than the distance between the leaflets). This effect has implications for the analysis of shape and deformation of freely suspended and flowing red blood cells.

Lipid Bilayers↗
PubMed1988

Effects of shear rate on rouleau formation in simple shear flow.

A kinetic equation for rouleau formation in a simple shear flow is derived, based on several assumptions. These are (a) colliding rouleaux stick to one another with a certain probability to form a single rouleau; (b) simultaneous collisions between more than two rouleaux are negligible; (c) rouleaux are broken by a viscous force exerted by the suspending fluid on the surfaces of rouleaux; (d) when a rouleau is broken by viscous forces, only two fragments are formed. Based on a simple mathematical model, collision rate, sticking probability and degradation rate are obtained as functions of applied shear rate. From the solution of the kinetic equation, the average size of rouleaux is obtained as a function of time with shear rate as a parameter. It is shown that the average size of rouleaux increases monotonically with increasing time and tends to an equilibrium size. The average size of rouleaux in a dynamical equilibrium decreases monotonically with increasing shear rate and tends to one cell as shear rate approaches infinity. It is also found that the initial rate of rouleau formation increases with increasing shear rate at very low shear rate, but this trend is reversed at higher shear rates. The theoretical results are compared quantitatively with experimental data.

Erythrocyte Aggregation↗
PubMed1987

Flow-dependent rheological properties of blood in capillaries.

Velocity-dependent flow of human red blood cells in capillaries with inside diameters of 4 to 8 micron is described theoretically. Cells are assumed to flow in single file, with axisymmetric shapes. Plasma flow in the gaps between cells and vessel walls is described by lubrication theory. The model takes into account the elastic properties of red cell membrane, including its responses to shear and bending. Cell shape is computed numerically as a function of tube diameter and cell velocity over the range 0.001 to 10 cm/sec. Relative apparent viscosity and dynamic hematocrit reduction (Fahraeus effect) are also computed. Since effects of interactions between cells are neglected, the Fahraeus effect is independent of hematocrit, while viscosity varies linearly with hematocrit. At moderate or high cell velocities, about 0.1 cm/sec or more, cell shapes and rheological parameters approach flow-independent limits. At lower velocities, cells broaden as a result of membrane shear and bending resistance and approach the walls more closely. Consequently, apparent viscosity increases with decreasing flow rate. Predicted values are in agreement with in vitro experimental determinations. Flow cessation is not predicted to occur in uniform tubes at positive driving pressures. Elastic deformational energies associated with red cell shapes are computed, leading to estimates of the pressure difference required to drive red cells past typical irregularities in capillary lumen cross sections. The hindrance to flow resulting from such structural irregularities represents a potential rheological mechanism for cessation of capillary flow at very low driving pressures.

Blood Flow Velocity↗
PubMed1987

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P less than or equal to 0.0001), percent type I fibers (r = 0.29; P less than 0.02), and percent type 2B fibers (r = -0.38; P less than 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P less than or equal to 0.0001; r = -0.47, P less than or equal to 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -0.39; P less than 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

Adipose Tissue↗
PubMed1987

Hematocrit fluctuations within capillary tubes and estimation of Fåhraeus effect.

Experimental and theoretical approaches were used to study hematocrit fluctuations in blood flowing along a uniform microvessel. In the experimental studies, human blood cell suspensions were passed along glass tubes with inside diameters 9.8 micron to 16.8 micron. A characteristic pattern of hematocrit fluctuation was observed in the neighborhood of white blood cells, the cell being preceded by a 'plasma gap' with reduced hematocrit and followed by a 'train' of increased hematocrit. The passage times of trains and plasma gaps and the hematocrits within the plasma gaps were determined by microphotometry. From these data, train hematocrits were deduced, expressed as equivalent discharge hematocrits. They ranged from the feed hematocrit to a value of more than 0.8 and were found to vary inversely with white cell velocity at a given flow rate. A theoretical model was developed which relates train formation to the Fåhraeus effect. The Fåhraeus effect is the reduction of tube hematocrit (HT) below discharge hematocrit (HD) which occurs in capillary tubes because the mean velocity of the red blood cells (VRBC) is higher than the mean bulk flow velocity (VB). The ratio of these velocities decreased with increasing hematocrit, and it is shown that train hematocrit is sensitive to this hematocrit-dependence. Increased hematocrit in trains behind slowly moving white cells is associated with reduced red cell velocity in the trains. From the dependence of train hematocrit on white cell velocity, the variation of Fåhraeus effect with hematocrit was deduced. The results were shown to be consistent with a model for the Fåhraeus effect in which VRBC/VB varies linearly with discharge hematocrit HD. In addition, the Fåhraeus effect was found to be approximately independent of vessel diameter over the range examined.

Biomechanical Phenomena↗
PubMed1984

Epidermal taurine transport in marine mussels.

We examined the structural specificity and kinetic characteristics of epidermal taurine transport in the marine mussels Mytilus edulis and M. californianus. The gill was the primary site of taurine uptake in both species, responsible for 70% of the accumulation of radioactively labeled substrate. Taurine transport was inhibited by short-chain beta-amino acids, including beta-alanine and beta-aminobutyric acid (beta-ABA), and by gamma-ABA; alpha-neutral, acidic, and basic amino acids had no effect on this transport. The uptake process was clearly a saturable phenomenon and was adequately described by Michaelis-Menten-type kinetics in both intact animals and isolated preparations of gill. The maximal rates of taurine uptake, expressed per gram of gill tissue, were 8.4 and 3.2 mumol X g-1 X h-1 for M. edulis and M. californianus, respectively. In intact mussels the half-saturation constant for both species ranged from 5 to 8 microM. A mathematical model was developed that describes the epidermal transport of taurine in the gill of the actively pumping mussel. The model takes into account the geometry and pattern of water flow in the gill. Calculations based on this model indicate that because of the convective movement of water through the gill, the actual Michaelis constant of the taurine transporter must be much lower (i.e., 0.5-2.5 microM) than the half-saturation constants determined with intact animals and isolated gills. The model also predicts that the presence of the transporter in the gill can result in a significant reaccumulation of taurine lost from the gill by passive diffusion. We suggest that epidermal taurine transport is involved with maintenance of the high concentrations of this compound commonly associated with gill tissue in mussels.

Amino Acids↗
PubMed1983

The motion of close-packed red blood cells in shear flow.

Experimental and theoretical results are presented concerning the motion of close-packed red blood cell suspensions subjected to steady simple shear flow. The behavior of the suspension was observed microscopically using a cone-and-plate rheoscope. At moderate and high shear rates the cells show a fairly orderly arrangement, each appearing polygonal in the field of view. An idealized theoretical model for the suspension is developed, in which each cell is a 14-sided polyhedron of varying shape, but with constant surface area and volume. Tank-treading motion of the membrane is predicted, and an approximation to the motion is calculated which is consistent with the known mechanical properties of the membrane. It is shown that considerably more energy is dissipated in the membrane than in the cytoplasm during tank-treading.

Erythrocyte Membrane↗
PubMed1983

The bulk rheology of close-packed red blood cells in shear flow.

A theoretical analysis is made of the dynamical behavior and bulk rheology of close-packed red blood cell suspensions subjected to simple shear flow. The model for the polyhedral cell shapes and tank-treading membrane motion developed in the companion paper (1) is used. The flow in the thin lubricating plasma layers between cells is analyzed taking into account the mechanical properties of the membrane at the corner regions of sharp membrane curvature. This leads to predictions for the apparent viscosity as a function of hematocrit and shear rate. Good agreement with experimental results is obtained at moderate and high shear rates (above 20 s-1). At lower shear rates, a rapid rise in apparent viscosity has been found experimentally, and the mechanisms leading to this behavior are examined.

Blood Viscosity↗
PubMed1983

Flow of red blood cells in narrow capillaries: role of membrane tension.

A theoretical model is developed to describe blood flow in narrow capillaries, with inside diameters 3 microns to 6 microns. Each red blood cell is assumed to have axisymmetric geometry, and fixed surface area and volume. Cell velocities in the range 1 mm s-1 or higher are assumed, and the stress in the cell membrane is approximated by an isotropic tension. This tension is assumed to fall to zero at the concave trailing end of the cell, except in vessels whose diameter is near the minimum for passage of the cell. In the latter case, a separate analysis is used, in which the cell is effectively rigid and fully distended at each end. Lubrication theory is used to describe the plasma flow in the narrow gap between the cell and the vessel wall. Good agreement is obtained between predicted values of the tube hematocrit and apparent viscosity and published experimental values for these parameters.

Capillaries↗
PubMed1981

Mechanics of blood flow.

The historical development of the mechanics of blood flow can be traced from ancient times, to Leonardo da Vinci and Leonhard Euler and up to the present times with increasing biological knowledge and mathematical analysis. In the last two decades, quantitative and numerical methods have steadily given more complete and precise understanding. In the arterial system wave propagation computations based on nonlinear one-dimensional modeling have given the best representation of pulse wave propagation. In the veins, the theory of unsteady flow in collapsible tubes has recently been extensively developed. In the last decade, progress has been made in describing the blood flow at junctions, through stenoses, in bends and in capillary blood vessels. The rheological behavior of individual red blood cells has been explored. A working model consists of an elastic membrane filled with viscous fluid. This model forms a basis for understanding the viscous and viscoelastic behavior of blood.

Animals↗