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To assess the responses of different growth factors on cerebral neocapillary density (NCD), cerebral angiogenesis was induced in mice using growth factors, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) at a concentration of 6 ng/ml each. Intravital fluorescence videomicroscopy was used to quantitatively evaluate microhemodynamic parameters such as diameter and red cell velocity. The gel–nylon mesh-sandwich system was implanted over the exposed cortex. After incubation for different periods of time (days 7, 14 or 28), fluorescein isothiocyanate (FITC)-labeled red cells were injected through a carotid artery and the neocapillaries on the upper surface of the nylon mesh were observed under a fluorescence videomicroscope. Based on the recorded videoimages, we evaluated the density, diameter and red cell velocity of the neocapillaries. The NCD in the bFGF group on day 7 was significantly higher than that in the PDGF group on day 7 (P < 0.01). The NCD (index) reached 100% on day 14, while it reduced significantly in both the groups on day 28. The neocapillary diameter was greater than that of the pre-existing capillaries on day 7. On day 14, a clear difference appeared in the capillary density between large and small vessels. The red cell velocity increased with the number of days after incubation. The response of cerebral neocapillaries to acetylcholine was measured after 28 days of incubation with growth factor bFGF and with PDGF. The red cell velocity increased significantly from its basal value in the PDGF group. These results suggest that the neocapillaries in the PDGF group matured earlier than those in the bFGF group.

Inflammation of the airway is thought to be one of the main factors contributing to the bronchial hyperresponsiveness which is characteristic for allergic asthma. Leukocyte adhered to vascular endothelium, which is caused by the interaction of adhesion molecules, is necessary for inflammatory cells infiltration. To elucidate the mechanism of leukocyte infiltration in asthma, we developed an animal model of asthma by using Wistar rats. In this model the leukocyte adhered to tracheal venular endothelium was assessed by in vivo microscopic observation. The results showed that the number of leukocytes adhered to tracheal venular endothelium increased significantly in asthmatic rats, as compared with those of controls, and it was accompanied by a significant inflammatory cell infiltration in lung tissue. It is concluded that the increase of leukocyte adhered to venular endothelium is pivotal in inflammatory cell infiltration in asthmatic rats. Copyright © 1996 Elsevier Science Ltd

Two diameters of vessel and red cell column in cerebral microvessels (> 29.8 microns in diameter) of cat were measured together with red cell velocity, using a two fluorescent tracer method. A fluorescein isothiocyanate (FITC)-labeled red cell was adopted as a flow tracer to measure the cell velocity with a dual window technique. Based on the fluorescence image, the red cell column diameter was measured. Plasma was stained with rhodamine-B isothiocyanate (RITC)-labeled dextran to measure the vessel diameter. The thickness of the cell-free plasma layer could be determined from the difference of the two diameters. The obtained thickness of the cell-free layer was not described by a simple function of vessel diameter or red cell velocity; it was dependent on the pseudo shear rate defined by the ratio of cell velocity to vessel radius. The layer thickness increased with a decrease in the pseudo shear rate.

A fine structure of blood flow through a curved vessel with an aneurysm was studied in in vitro experiments in relation to rheological factors of arterial diseases such as arteriosclerosis or thrombosis. On the basis of the in vivo data related to cerebral circulation, red blood cell suspension was flowed through curved vessel models with an asymmetrical aneurysm. Flow visualization was made with a microscope 16 mm cinecamera-TV monitor system, and the velocity profile was measured using the laser Doppler velocimeter. Vortices induced in aneurysm influenced flow structure and velocity at the presence of the secondary flow due to the vessel curvature. This suggests strongly that blood flow in curved arteries with an aneurysm must be understood under the influence of the secondary flow.

Effects of high osmotic media on the shape and deformability of RBC were examined for determining increasing factors of blood viscosity. Dog blood and Urographin (a hypertonic contrast medium) were used; the plasma osmolality was changed by Urografin suspended in blood. The viscosity was measured for normal RBC and glutaraldehyde-treated RBC suspensions with a cell volume concentration. The RBC deformability was evaluated from the difference in viscosity between the two suspensions. It was shown that normal RBC suspension increased the viscosity with increase in osmolality at high shear rate; hardened RBC suspension decreased the viscosity with increase in osmolality. It was concluded that the RBC deformability decreased with increasing osmolality.

Filtrability of a suspension of polymorphonuclear leukocytes (PMNs) was examined in a Nuclepore membrane filtration system utilizing a gradually reduced pressure difference with or without an additional negative pressure. The filtration process was continuously recorded using a TV-video system for data analysis. The PMN content in the filtrate was directly measured. The pressure-flow relation was analyzed in terms of the relative resistance of the PMN suspension to that of the suspending medium. The relative resistance of the PMN suspension increased with an increase in the filtered volume until it approached infinity at the level of low pressure difference (2.8 - 0 cmH2O). The remarkable increase in flow resistance was closely associated with the plugging of PMNs in the membrane pores. At high pressure differences (12.8 - 10 cmH2O, 7.8 - 5 cmH2O), the relative resistance increased up to finite values, as the filtered volume increased. The variation in the relative resistance was greatly dependent upon the pressure difference or the flow condition. The amount of filtered cell fraction increased with an increase of additional pressure, indicating that the relative resistance was changed according to the rate of PMN plugging and dislodging in the pores of the membrane.

Blood cells filtration with decreasing pressure under gravity was studied for evaluation of the cell fluidity or deformability at a low shear state. A continuum approach was made to the flow and pressure in the filter at the low flow state to relate macro- and micro-scopic quantities. The mass conservation law of each species provided a set of differential equations with respect to the pore fraction and filter resistance. The numerical calculation was made for various values of hematocrit and leukocrit. It was shown that the filter resistance might be increased with decreasing pressure, resulting from both red and white cells. The leukocrit, more than 0.05% white cells, may influence the filtration, depending upon the cell deformation. Even in the absence of the white cell, a decrease in pressure increased the filter resistance markedly. The present result indicates that single red cell shows a nonlinear behavior of flow in pores at the low pressure level.

Blood rheology at a stagnation point is studied in views of microhemorheology. Special emphasis is put on the effect of both non-Newtonian and unhomogeneous properties of blood on the fine structure of blood flow impinging on the wall. It is shown that "non-flow" region exists just at the stagnation point due to the non-Newtonian viscosity when its yield stress is large enough, compared with the viscous stress far from the wall. When the yield stress becomes negligibly small, RBC and plasma behave individually near the stagnation point; RBC is deviated from the plasma streamline and impinges on the wall. Finally, a microhemorheological factor of legional metabolic disorder is discussed on basis of the fine structure near a stagnation point.

The motion of a red blood cell in a plane Couette flow is studied theoretically, introducing a two-dimensional microcapsule model for the cell. It is assumed that the microcapsule is deformed into an elliptical shape with a constant area and that its membrane moves like a tank-tread around the interior. The flow fields both inside and outside the microcapsule are analyzed using the finite element method in the Stokes equations and the obtained viscous forces on the membrane are used to determine its deformation and tank-treading motion. It is shown that a decrease in viscosity ratio of internal to external fluids causes the microcapsule to be more elongated, with its inclination angle increasing, whereas the microcapsule becomes more elongated at a smaller inclination angle with a longer tank-treading period as the elastic compliance of the membrane or the shear rate of the Couette flow increases. The force acting on the wall is also examined in relation to the abnormal viscosity of blood.

A mathematical model is developed to elucidate micro-hemorheological factors of the oxygen transport between blood and tissue. A two-fluids model is introduced for capillary blood flow, including the non-equilibrium and relative motion between red blood cell (RBC) and plasma. A capillary-tissue unit is devised to describe the oxygen supply to tissue from a couple of capillaries with symmetric antiparallel input and output. Non-equilibrium flows are examined numerically on the basis of the model for various geometrical and dynamical parameters such capillary hematocrit, RBC velocity and flux. It is found that both RBC flux and capillary hematocrit have important influences on the oxygen transfer to tissue. Especially under low capillary hematocrit flow, the lowest oxygen pressure within tissue may appear at the maximal diffusional distance from the capillary between arterial and venous side.

The supply of oxygen to tissue from capillaries may be influenced by hemorheological factors. A hemorheological model is developed for elucidating which factors play a major role in the oxygen transport to tissue. For a capillary tissue unit, a modified cylindrical model of Krogh is used. For blood, two fluids model of red blood cells (RBCs) and plasma is used where hemoglobin release effect is included. Non-equilibrium flows as well as equilibrium flows are examined for various parameters (total flow Q or RBC velocity Vr, discharge hematocrit Hd and capillary hematocrit Hc). In equilibrium flow, Hd and Q determine the oxygen transport. In non-equilibrium flow, Hc also becomes important. Especially, hemoglobin release effect becomes significant in low Hc flow, which affects the area of lethal region in tissue.