Capillary Blood Cell Research Articles

Interaction between micro-particles in Oseen flows by the method of fundamental solutions

The aim of this study is to investigate interactions between two identical spherical particles in viscous flows using the method of fundamental solutions (MFS). Oseen flow is considered when the Reynolds number is small. Axis-symmetric problems are studied where the flow is parallel to the axis joining the centre of the two spheres. Fluid velocity and pressure can be represented by a linear combination of fundamental solutions, i.e. ring-distributed point forces on a fictitious boundary outside of the fluid domain. The densities of these point forces are determined by enforcing boundary conditions on the capillary wall and the surface of the particles. The MFS approach avoids boundary integrations and, therefore, achieves a much simpler system matrix. Interactions between two spherical particles in a boundless flow field as well as in a small capillary with a parabolic flow are investigated to illustrate the simplicity and accuracy of the method. Forces acting on each of the two particles are calculated at different Reynolds numbers and with varying distances between the two particles. It is found that for small but non-zero Reynolds numbers, the drag force on the leading particle is always bigger than that on the trailing particle. This agrees to experimental observations that blood cells in capillaries form columns of cells in steady state. Furthermore, it is found that the difference in the drag force on the leading and the trailing particles is bigger at larger Reynolds number. At given Reynolds number, the difference in dragging forces decreases as the distance between the two particles increases. The Oseen flow approximation enables the application of the MFS in studying interactions between particles in small but non-zero Reynolds number flows. The proposed MFS method is simple to implement and gives satisfactory results.

Movement of a spherical cell in capillaries using a boundary element method

This study aims to investigate the translation and rotation of a spherical particle in capillaries and overcomes limitations in previous studies by using a boundary element method. The capillary, a straight cylindrical tube, is filled with a Newtonian viscous fluid. A spherical particle is arbitrarily positioned in the capillary either co-centrically or eccentrically and is free to translate and rotate. Flow in the capillary is first assumed to be caused solely by the movement of the sphere under the gravity. When a steady state is reached, the net force and torque on the sphere are zero. The translating velocity and rotation of the particle are calculated from equilibrium equations. For a co-centric sphere, our result agrees to Bohlin's analytical solution (Bohlin, 1960) and the difference is less than 1%. For an eccentrically positioned sphere in the tube, there are no analytical solutions unless the eccentricity is infinitesimal. Results by boundary element method (BEM) give an improved estimations on the velocity and rotation of the sphere than earlier results by a boundary singularity method (BSM), particularly when the clearance between the tube and the sphere becomes small. Movement of a spherical particle in a capillary driven by a pressure gradient is further investigated, which has closer relevance to movement of blood cells in capillaries. The current study using BEM enables investigation on cell movement in close proximities of the capillary wall.

Elastohydrodynamic Lubrication in Biological Systems

Elastohydrodynamic lubrication (EHL) appears to be an important mechanism in various biological systems. In this paper, a few examples will be selected to illustrate the biological applications of EHL: microcirculation of red blood cells in capillaries, blinking of eye and contact lens, and respiratory motion between pleural surfaces and articulation in synovial joints. It is shown that the relatively large elastic deformation of the bearing surfaces associated with relatively compliant biological tissues is responsible for the major contribution of fluid film action to the lubrication at both tissue and cellular levels. Under unfavourable lubrication conditions, the articulating surfaces can be protected by the powerful effect of micro-EHL in smoothing out surface asperities and further by the glycocalyx present on the biological surfaces.

Hemoglobin-Vesicles as Oxygen Carriers: Influence on Phagocytic Activity and Histopathological Changes in Reticuloendothelial System

Hemoglobin-vesicles (HbV) have been developed for use as artificial oxygen carriers (particle diameter, 250 nm) in which a purified Hb solution is encapsulated with a phospholipid bilayer membrane. The influence of HbV on the reticuloendothelial system was studied by carbon clearance measurements and histopathological examination. The HbV suspension ([Hb] = 10 g/dl) was intravenously infused in male Wistar rats at dose rates of 10 and 20 ml/kg, and the phagocytic activity was measured by monitoring the rate of carbon clearance at 8 hours and at 1, 3, 7, and 14 days after infusion. The phagocytic activity transiently decreased one day after infusion by about 40%, but it recovered and was enhanced at 3 days, showing a maximum of about twice the quiescent level at 7 days, and then returned to the normal value at 14 days. The initial transient decreased activity indicates a partly, but not completely, suppressed defensive function of the body. The succeeding increased phagocytic activity corresponds to the increased metabolism of HbV. The histopathological examination with anti-human Hb antibody, hematoxylin/eosin, and oil red O stainings showed that HbV was metabolized within 7 days. Hemosiderin was very slightly confirmed with Berlin blue staining at 3 and 7 days in liver and spleen, though they completely disappeared at 14 days, indicating that the heme metabolism, excretion or recycling of iron proceeded smoothly and iron deposition was minimal. Electron microscopic examination of the spleen and liver tissues clearly demonstrated the particles of HbV with a diameter of about 1/40 of red blood cells in capillaries, and in phagosomes as entrapped in the spleen macrophages and Kupffer cells one day after infusion. The vesicular structure could not be observed at 7 days. Even though the infusion of HbV modified the phagocytic activity for 2 weeks, it does not seem to cause any irreversible damage to the phagocytic organs. These results offer important information for evaluating the safety issues of HbV for clinical use.

Quantitative assessments of physiological and biological parameters in psoriatic lesions and its correlations to the clinical severity of psoriasis.

Twenty-nine psoriatics were examined using a model with clinical, physiological and pathological assessment parameters. The three parts in this assessment model include: (1) clinical assessment: psoriasis area and severity index (PASI); (2) assessment of skin physiology and microcirculation: water content of stratum corneum, water-holding capacity of stratum corneum, transepidermal water loss, intravital dynamic videocapillaroscopy-measuring the capillary diameters and blood cell velocity in proximal nailfold of ring finger, and fluorescence angiography-measuring transcapillary Na-fluorescein(NAF) diffusion; and (3) immunohistochemistry examination: markers of proliferation (Ki67Ag), differentiation (involucrin), and inflammation (neutrophil elastase, intercellular adhesion molecule-1(ICAM-1), endothelial leukocyte adhesion molecule-1(ELAM-1)). Our results showed both the transcapillary diffusion of NAF and the expression of cell markers-dermal neutrophil elastase, epidermal ELAM-1 and Ki67Ag--correlated significantly to PASI scores (P < 0.05, linear regression). According to our results, the increased capillary permeability and inflammation markers, and enhanced expression of Ki67Ag correlated very well with PASI score. These markers could serve as alternative methods for assessment of the clinical severity of psoriatic patients.

Near-infrared confocal laser scanning microscopy of bladder tissue in vivo

Objectives. To assess the potential of a near-infrared confocal laser scanning microscope (CLSM) for imaging bladder tissue in vivo. Methods. Confocal images of the exposed bladder of male Sprague-Dawley rats were obtained with a CLSM. To minimize tissue motion, the bladder was placed in light contact under an objective lens housing, and the top surface was lightly flattened with a coverslip. Images were obtained from the outer and inner layers of the bladder wall with a lateral resolution of 0.5 to 1 μm and an axial resolution (section thickness) of 3 to 5 μm. The confocal images were later correlated with routine histologic studies. Results. The CLSM allows imaging of the urothelium, the superficial and deep portions of the lamina propria, the muscularis propria, and the serosa of the bladder wall in vivo. Urothelial cells, collagen bundles and fibers, muscle, and circulating blood cells in capillaries and larger blood vessels are easily visualized. The confocal images correlated well with the histologic studies. Conclusions. Confocal microscopy allows real-time, high-resolution, high-contrast imaging of cellular and structural morphologic features to a maximal depth of 300 μm within the bladder wall in vivo. Artifacts caused by tissue motion can be minimized with a bladder–objective lens contact housing.

Early changes in performance, blood flow and capillary fine structure in rat fast muscles induced by electrical stimulation.

1. Muscle blood flow, capillary fine structure and performance were investigated in the early stages of chronic indirect electrical stimulation of ankle flexors in the rat. 2. The fast muscles tibialis anterior (TA), extensor digitorum longus (EDL) and extensor hallucis proprius (EHP) were unilaterally stimulated via the right common peroneal nerve at 10 Hz and supramaximal voltage for 8 h a day for 2, 3 or 7 days and compared with muscles from control animals. 3. Muscle blood flow (MBF) was estimated at rest and during contractions by radioactive microspheres. It was higher at rest than in unstimulated controls only in muscles stimulated for 2 days; during contractions it was higher in some muscles stimulated for 3 days than in controls, and in all muscles by 7 days (192 +/- 17 vs. 149 +/- 12 ml (100 g)-1min-1 in controls). 4. Electron microscopical evaluation of individual capillaries in EHP fixed by superfusion in situ revealed thickening of capillary endothelium and decreased lumen volume in muscles stimulated for 7 (P < 0.005) but not 3 days. Significantly smaller capillary size indicates the presence of newly formed capillaries. 5. Isometric twitch tension, recorded from combined TA and EDL in stimulated and contralateral legs during 5 min contractions at 4 Hz, gradually declined from 175 +/- 9 to 99 +/- 4 kN m-2 after 7 days of stimulation (P < 0.05) while the fatigue index, calculated as (final twitch tension/peak twitch tension) x 100, increased from 69.8 +/- 3.4 to 90 +/- 3.0 % (P < 0. 05). No significant changes in the fatigue index occurred in muscles stimulated for 2 or 3 days. 6. Lower peak tension, but not fatigue index or MBF, was also observed in muscles contralateral to those stimulated for 3 and 7 days, which thus do not represent appropriate controls. 7. We conclude that the high resting blood flow found in muscles stimulated for 2 days may initiate the capillary growth reported previously, while the relatively modest increase in MBF during contractions in muscles that had been stimulated for 7 days may be due to increased capillary supply. Swelling of the capillary endothelium and decreased volume of the capillary lumen may result in an increased proportion of time spent by red blood cells in capillaries, which would improve oxygen extraction.

Movement of spherical particles in capillaries using a boundary singularity method

As a first step to investigate the motion of blood cells in capillaries, we have studied the movement of a spherical particle falling in a vertical cylindrical tube using a boundary singularity method. The tube is filled with a Newtonian viscous fluid which would otherwise be stationary. The Reynolds number of the flow is much less than one. The sphere falls at arbitrary positions in the tube and is free to rotate. Point forces, Stokeslets, with unknown strength and direction, are distributed on the surfaces of the tube and the sphere. By forcing the flow field generated by all of the Stokeslets to satisfy proper boundary conditions, we solve for the strength and direction of each Stokeslet. The velocity, U, and rotation, Ω, of the sphere are then calculated from a force and a torque balance. For a sphere falling on the axis of the tube, our results agree with Bohlin’s approximate solution. When the sphere takes eccentric positions in the tube, it rotates as it translates down the tube, the direction of rotation being opposite to that it would have if the sphere rolled along the nearest side of the tube. This results from the zero net torque on the sphere and facilitates flow passing around the sphere. As the distance between the centre of the sphere and the axis of the tube increases, Ω increases almost linearly, while U changes little. When the radius of the tube increases, U increases and approaches the Stokes velocity, while Ω decreases rapidly. The boundary singularity method is relatively simple compared to other numerical methods and can be extended much more easily to the complex geometries typical of blood cells.

Motion of red blood cells in capillaries with variable cross-sections.

Red blood cells undergo continual deformation when traversing microvessels in living tissues. This may contribute to higher resistance to blood flow observed in living microvessels, compared with that in corresponding uniform glass tubes. We use a theoretical model to simulate single-file motion of red cells though capillaries with variable cross-sections, assuming axisymmetric geometry. Effects of cell membrane shear viscosity and elasticity are included, but bending resistance is neglected. Lubrication theory is used to describe the flow of surrounding plasma. When a red cell encounters a region of capillary narrowing, additional energy is dissipated, due to membrane viscosity, and due to narrowing of the lubrication layer, increasing the flow resistance. Predicted resistance to cell motion in a vessel with periodic constrictions (diameter varying between 5 microns and 4 microns) is roughly twice that in a uniform vessel with diameter 4.5 microns. Effects of transient red cell deformations may contribute significantly to blood flow resistance in living microvessels.

ヒト顎関節標本におけるＴＧＦ‐βの局在について（免疫組織化学的研究）

In this study, we immunohistochemically investigated the expression of TGF-β in 16 human temporomandibular joint (TMJ) discs.The specimens were obtained at discectomy and autopsy.TGF-β showed three types of expression:(1) at the blood cells in capillaries;(2) around fibrocytes and at the lacunae of chondrocytes in the disc; and (3) at the stroma of the hyperplastic synovial membrane and proliferating synovial membrane.The first two types were observed in all cases, including control.The last type was seen only in internal derangement of the TMJ.The results suggest that TGF-β is involved in the pathogenesis of synovitis.

Acute respiratory failure in patients treated for babesiosis.

Babesiosis is a tick-borne protozoal disease with infrequent clinical complications. We report three cases of noncardiogenic pulmonary edema in patients from Nantucket Island, MA, with a history of Lyme disease and review the clinical presentation of babesiosis and its treatment. Respiratory complications in our patients, as well as in the four previously reported cases in the literature, occurred a few days after initiation of medical therapy. We hypothesize that the pathophysiology of the pulmonary edema is multifactorial, due to decreased deformability of the infected erythrocytes, increased cytoadherence of red blood cells in capillaries and venules, and a possible role of excessive production of certain cytokines, such as tumor necrosis factor and interleukin-1.

Effect of low dose oxygent added to blood on muscle VO2max.

Federspiel et al.1 have suggested that the plasma space between red blood cells in capillaries does not contribute significantly to diffusive O2 transport out of the muscle vasculature due to the low plasma solubility of O2. To test this, we pump-perfused in situ isolated canine gastrocnemius muscle stimulated electrically to produce VO2 max under two conditions [with blood flow 120 ml 100 gm−1 min−1, [Hb] 8.7 gm dl−1 and PaO2 ~ 500 torr in each case]: A) control, and B) with Oxygent (perflubron emulsion, Alliance) added at 6 gm perflubron/70 ml. Total plasma O2 solubility was taken to be 0.003 ml 100 ml−1 torr−1 in A) and computed to be 0.005 ml 100 ml−1 torr−1 in B) from the increase in total [O2] in B) compared to A).KeywordsTotal PlasmaDiffuse CapacityBlood Flow RatePlasma SpaceFlow ExtractionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Folding of red blood cells in capillaries and narrow pores

The geometric features of red blood cells in narrow channels in vivo and in vitro were studied by electron microscopy. In rabbit myocardial capillaries about half of the red cells were folded. In polycarbonate filters with pore diameters of 2.2-4.5 microns approximately one third of the trapped red blood cells were folded. The frequency of folding did not depend on the applied pressure, which ranged from 0.1 to 8.0 cm H2O. The folding of the red blood cells in filter pores was used to estimate the bending stiffness of the membrane. An analysis based on the large deformation theory of bending of an elastic sheet was developed. Using pressures of 0.2 and 1.0 cm H2O, the bending stiffness of human red cell membranes was estimated to be approximately 2.4 - 11.6 x 10(-12) dyn-cm, which is in good agreement with other methods. A limiting radius of curvature of about 85 nm was found at higher pressures.

A mathematical model of the flow of blood cells in fine capillaries

A description of the flow of blood cells in the capillary blood vessels is presented. The model employs the lubrication theory approach first suggested by Lighthill ( J. Fluid Mech. 34, 113–143, 1968). The work of previous investigators is extended by taking into account a wider range of the elastic deformations which affect the cell.

Redistribution of Intraorgan Blood Flow in Acute, Hyperdynamic Porcine Endotoxemia

In a standardized porcine model of acute, hyperdynamic endotoxemia the distribution of intraorgan blood flow within heart, kidney and brain was analyzed. Twelve pigs received either short-term (23 min) or long-term (205 min) continuous intravenous infusion of endotoxin (Salmonella abortus equi). A high cardiac output/low peripheral resistance state was maintained throughout the 3.5 h observation period. Total organ blood flow in heart, kidney and brain remained high; however, already small amounts of endotoxin provoked a significant redistribution of intraorgan blood flow within the left ventricle and the kidney. These characteristic alterations were absent in a control group of 5 animals subjected to the same protocol, but receiving 0.9% saline instead of endotoxin. Deterioration of respiratory function developed exclusively after continuous intravenous endotoxin infusion over 205 min, indicating incipient organ failure. Using electron microscopy, endothelial cells swelling and entrapment of blood cells in capillaries of the midmyocardium as well as severe ultrastructural damage in the kidney could be demonstrated already after 90 min of endotoxemia in two additional animals. It is concluded that already in the initial phase of acute endotoxemia, in the presence of high cardiac output and high global organ blood flow microcirculatory deterioration and organ failure develops. As small amounts of endotoxin are capable of inducing these alterations, earliest possible diagnosis of endotoxemia should be achieved in critically ill patients.

Quantitation and karyometry of cerebral neuroglia and endothelial cells in liver cirrhosis and in the hepatosplenic schistosomiasis mansoni

A morphological, karyometric, and quantitative study of cerebral neuroglia and endothelial cells of blood capillaries was done in cirrhotic and in hepatosplenic schistosomotic human autopsied cases. Cluster analysis applied to them revealed three subgroups (cirrhosis and schistosomiasis polar groups and one intermediate). The comparison of these three groups with a control revealed increased numbers of astrocytes, oligodendrocytes and endothelial cells, but no nuclear enlargement in the schistosomiasis group; the cirrhosis group exhibited a pronounced nuclear enlargement of both astrocyte and oligodendrocytes but no increase in cell numbers. The intermediate group, which encompasses the majority of pathological cases, is heterogeneous but on average behave as the cirrhosis group in that nuclear enlargement, but no increase in cell numbers, was noted. Such changes could represent a response of the nervous system to the metabolic disturbances present in hepatic and/or portal-systemic encephalopathy. There was a positive correlation between glial and endothelial cell numbers in cerebral cortex, suggesting a functional relationship between the glial cells and the capillary bed. This study points out the importance of clustering the cases, because the physiopathological status of individuals belonging to the same nosological condition can be different. Comparisons considering this aspect should be useful in understanding the progression of the pathological process.

Numerical study of asymmetric flows of red blood cells in capillaries

Experimental studies have shown that red blood cells in capillaries may flow in single-file or multifile arrangements. To model multifile rheological behavior, the asymmetric flows of rigid circular cylinders in a two-dimensional channel are studied by numerical analysis. The rigid circular cylinders are arranged off-center in a channel in a row or two rows with equal spacings. The motion of the suspending fluid is analyzed by the finite element method applied to the Stokes equation, and the motions of the particles are simultaneously determined under the zero force and zero moment conditions appropriate to neutorally buoyant particles. The velocity difference between the particles and the bulk flow is significantly affected by the arrangement of the particles. The particle velocity is reduced as the particles are moved away from the centerline of the channel. At a constant concentration of the particles, the relative apparent viscosity of an off-center arrangement is considerably higher than that of a single-file flow of the particles located on the centerline of the channel. The present results suggest that changes of the radial distribution of red cells following through narrow vessels may lead to alterations of the Fahraeus and Fahraeus-Lindqvist effects.

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 μm 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.

Effect of naloxone on microcirculatory behavior during irreversible hemorrhagic shock

Thirty-six male Sprague-Dawley rats were divided into three groups ( n = 12): simple hemorrhagic shock group, saline-treated group, and naloxone-treated group. Synchronous videotape recording with two cameras was used to observe the relationship between the change of blood pressure and that of microcirculation of cremaster muscle. It has been suggested that the temporary plugging of capillaries by WBC may be the explanation for no reflow in microvessels after transfusion and infusion during the irreversible stage of shock. Administration of naloxone (2 mg/kg iv) followed by reinfusion of the shed blood is associated with an increase in blood pressure and pulse pressure. Coincidentally, a pulsatile movement of the blood, impacted on the stationary blood cells in capillaries, eventually dislodges them and leads to reperfusion of capillaries. Thereafter systemic blood pressure and carotid artery red blood cell velocity were increased and remained stable. The 24-hr survival rate was significantly increased in the naloxone-treated group ( 10 12 ), as compared with that in the saline-treated group ( 1 12 ). The mechanism of naloxone treatment is discussed. The suggestion is advanced that the effects on cardiac and microcirculatory performance may influence each other, and that both contribute to the pathogenesis of irreversible hemorrhagic shock.

Ultrastructure of the proteoglycan component of the extracellular matrix in the intact mammary gland and in benign and malignant breast tumors

Proteoglycans (PG) were revealed by electron microscopy using cation dyes, Alcian blue and safranin O. In intact mammary gland of dogs, each histogenetic type of cells had its specific features in the ultrastructure of pericellular matrix proteoglycan component. A thin-stitched net, consisting of small PG granules and thin filaments has been observed in the pericellular space of secretory epithelium. A well-proportioned PG net is absent near fibroblasts and macrophages. Net-like PG structure is found in the endothelium, pericytes and adventitial cells of blood capillaries. Visual changes in PG-containing extracellular matrix are observed in the epithelium of mammary gland tumors.