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In previous studies we showed that intravenous infusion of Dextran 500 in the rat causes blunting of the velocity profile of red blood cells in venules at low shear rates. To determine whether this blunting is associated with the formation of red blood cell aggregates, we measured the length and width of particles in the venular flow stream at systemic hematocrits up to 20% with a high-speed video camera and a new image analysis technique. Data were obtained at various shear rates under normal (nonaggregating) conditions as well as after infusion of Dextran 500. Under normal conditions, particle length (parallel to the vessel axis) was 6.5 [+ or -] 2.7 [micro]m and width (perpendicular to the axis) was 6.1 [+ or -] 1.7 [micro]m, in agreement with published dimensions of individual red blood cells for this species. After Dextran 500 infusion, particle length and width increased significantly to 8.7 [+ or -] 5.1 and 10.4 [+ or -] 4.4 [micro]m, respectively. Particle dimensions were greater in the central region of the flow stream for both normal and dextran-treated blood and increased at low flow rates with dextran-treated blood. This study provides direct confirmation of aggregate formation at low shear in venules with high-molecular-weight dextran as well as an estimate of aggregate size and range. venous vascular resistance; in vivo blood theology; in vivo microscopy; red blood cell aggregation

Axial migration of red blood cells in small glass tubes can cause blood viscosity to be effectively independent of shear rate. However, this phase separation may not occur to the same degree in the venous network due to infusion of cells and aggregates at branch points. To investigate this hypothesis, we followed trajectories of fluorescently labeled red blood cells in the venular network of the rat spinotrapezius muscle at normal and reduced flow with and without red blood cell aggregation. Cells traveling near the wall of an unbranched venular segment migrated ~1% of the longitudinal path length without aggregation and migrated slightly more with aggregation. Venular segment length between branch points averaged three to five times the diameter. Cells in the main vessel were shifted centrally by up to 20% of diameter at branch points, reducing the migration rate of cells near the opposite wall to [is less than] 1% even in the presence of aggregation. We conclude that formation of a cell-free marginal layer in the venular network is attenuated due to the time dependence of axial migration and the frequent branching of the network. venous resistance; radial migration; red blood cell aggregation; in vivo fluorescence microscopy; venous network topology

Previous studies in skeletal muscle of the dog and cat have shown that venous vascular resistance changes inversely with blood flow and may be due mainly to red blood cell aggregation, a phenomenon present in these species. To determine whether red blood cell axial migration and sedimentation contribute to this effect, we viewed either vertically or horizontally oriented venules of the rat spinotrapezius muscle with a horizontally oriented microscope during acute arterial pressure reduction. With normal (nonaggregating) rat blood, reduction of arterial pressure did not significantly change the relative diameter of the red blood cell column with respect to the venular wall. After induction of red blood cell aggregation in the rat by infusion of Dextran 500, red blood cell column diameter decreased up to 35% at low pseudoshear rates (below ~5 [s.sup.-1]); the magnitude was independent of venular orientation. In vertically oriented venules, the plasma layer was symmetrical, whereas in horizontally oriented venules, the plasma layer formed near the upper wall. We conclude that, although red blood cell axial migration and sedimentation develop in vivo, they occur only for larger flow reductions than are needed to elicit changes in venous resistance. venous resistance; low shear flow; in vivo blood rheology; blood sludging; red blood cell core

Effect of erythrocyte aggregation on velocity profiles in venules. Am J Physiol Heart Circ Physiol 280: H222-H236, 2001.--A recent whole organ study in cat skeletal muscle showed that the increase in venous resistance seen at reduced arterial pressures is nearly abolished when the muscle is perfused with a nonaggregating red blood cell suspension. To explore a possible underlying mechanism, we tested the hypothesis that red blood cell aggregation alters flow patterns in vivo and leads to blunted red blood cell velocity profiles at reduced shear rates. With the use of fluorescently labeled red blood cells in tracer quantities and a video system equipped with a gated image intensifier, we obtained velocity profiles in venous microvessels (45-75 [micro]m) of rat spinotrapezius muscle at centerline velocities between 0.3 and 14 mm/s (pseudoshear rates 3-120 [s.sup.-1]) under normal (nonaggregating) conditions and after induction of red blood cell aggregation with Dextran 500. Profiles are nearly parabolic (Poiseuille flow) over this flow ra-te range in the absence of aggregation. When aggregation is present, profiles are parabolic at high shear rates and become significantly blunted at pseudoshear rates of 40 [s.sup.-1] and below. These results indicate a possible mechanism for increased venous resistance at reduced flow. venous resistance; blood constitutive equation; in vivo blood viscosity; in vivo fluorescence microscopy; wall shear stress

Diameter changes in skeletal muscle venules during arterial pressure reduction. Am J Physiol Heart Circ Physiol 279: H47-H57, 2000.--Previous studies in skeletal muscle have shown a substantial ([is greater than] 100%) increase in venous vascular resistance with arterial pressure reduction to 40 mmHg, but a microcirculatory study showed no significant venular diameter changes in the horizontal direction during this procedure. To examine the possibility of venular collapse in the vertical direction, a microscope was placed horizontally to view a vertically mounted rat spinotrapezius muscle preparation. We monitored the diameters of venules (mean diameter 73.8 [+ or -] 37.0 [micro]m, range 13-185 [micro]m) oriented horizontally and vertically with a video system during acute arterial pressure reduction by hemorrhage. Our analysis showed small but significant (P [is less than] 0.0001) diameter reductions of 1.0 [+ or -] 2.5 [micro]m and 1.8 [+ or -] 3.1 [micro]m in horizontally and vertically oriented venules, respectively, upon reduction of arterial pressure from 115.0 [+ or -] 26.3 to 39.8 [+ or -] 12.3 mmHg. The venular responses were not different after red blood cell aggregation was induced by Dextran 500 infusion. We conclude that diameter changes in venules over this range of arterial pressure reduction are isotropic and would likely increase venous resistance by [is less than] 10%. venous resistance; venous pressure; venous collapse; venous wall architecture; hemorrhage

Previous in vitro studies of blood flow in small glass tubes have shown that red blood cells exhibit significant erratic deviations in the radial position in the laminar flow regime. The purpose of the present study was to assess the magnitude of this variability and that of velocity in vivo and the effect of red blood cell aggregation and shear rate upon them. With the use of a gated image intensifier and fluorescently labeled red blood cells in tracer quantities, we obtained multiple measurements of red blood cell radial and longitudinal positions at time intervals as short as 5 ms within single venous microvessels (diameter range 45-75 [micro]m) of the rat spinotrapezius muscle. For nonaggregating red blood cells in the velocity range of 0.3-14 mm/s, the mean coefficient of variation of velocity was 16.9 [+ or -] 10.5% and the SD of the radial position was 1.98 [+ or -] 0.98 [micro]m. Both quantities were inversely related to shear rate, and the former was significantly lowered on induction of red blood cell aggregation by the addition of Dextran 500 to the blood. The shear-induced random movements observed in this study may increase the radial transport of particles and solutes within the bloodstream by orders of magnitude. shear-induced particle diffusion; red blood cell aggregation; in vivo fluorescence microscopy; solute transport; dispersion coefficient

Knowledge of the effects of red blood cell aggregation on blood flow in small vessels is crucial to a better understanding of resistance changes in the venous microcirculation. Recent studies on rat spinotrapezius muscle indicate that enhanced red blood cell aggregation, induced by dextran 500, significantly affects velocity profiles at pseudoshear rates (the ratio of mean velocity to diameter) less than 40 s-1. Since the use of a power-law model to describe these profiles does not provide a consistent rheological description, we have evaluated using the Casson model that has been widely used to characterize in vitro blood rheology. In the present study, we report experimental values of rat blood viscosity in the presence of dextran 500 and combine these in vitro measurements with previously obtained in vivo venular velocity profiles to determine whether the Casson model can provide a valid description of in vivo velocity profiles. Our analysis shows that the two-phase Casson model with a peripheral plasma layer is in quantitative agreement with experimentally obtained velocity profiles obtained in venules of rat spinotrapezius muscle under low flow rate. These results have implications for pathological low-flow conditions, such as hemorrhage and sepsis, and they quantitatively describe blunted velocity profiles and elevated flow resistance in postcapillary venules. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]