Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia

Responses to exchange transfusion using red blood cells (RBCs) with normal and reduced flexibility were studied in the hamster window chamber model during acute moderate isovolemic hemodilution to determine the role of RBC membrane stiffness in microvascular perfusion and tissue oxygenation. Erythrocyte stiffness was increased by 30-min incubation in 0.02% glutaraldehyde solution, and unreacted glutaraldehyde was completely removed. Filtration pressure through 5-microm pore size filters was used to quantify stiffness of the RBCs. Anemic conditions were induced by two isovolemic hemodilution steps using 6% 70-kDa dextran to a hematocrit (Hct) of 18% (moderate hemodilution). The protocol continued with an exchange transfusion to reduce native RBCs to 75% of baseline (11% Hct) with either fresh RBCs (RBC group) or reduced-flexibility RBCs (GRBC group) suspended in 5% albumin at 18% Hct; a plasma expander (6% 70-kDa dextran; Dex70 group) was used as control. Systemic parameters, microvascular perfusion, capillary perfusion [functional capillary density (FCD)], and oxygen levels across the microvascular network were measured by noninvasive methods. RBC deformability for GRBCs was significantly decreased compared with RBCs and moderate hemodilution conditions. The GRBC group had a greater mean arterial blood pressure (MAP) than the RBC and Dex70 groups. FCD was substantially higher for RBC (0.81 +/- 0.07 of baseline) vs. GRBC (0.32 +/- 0.10 of baseline) and Dex70 (0.38 +/- 0.10 of baseline) groups. Microvascular tissue Po(2) was significantly lower for Dex70 and GRBC vs. RBC groups and the moderate hemodilution condition. Results were attributed to decreased oxygen uploading in the lungs and obstruction of tissue capillaries by rigidified RBCs, indicating that the effects impairing RBC flexibility are magnified at the microvascular level, where perfusion and oxygenation may define transfusion outcome.     

Radial displacement of red blood cells during hemodilution and the effect on arteriolar oxygen profile

In this study, we assessed the magnitude of the erratic deviations in the radial position of red blood cells (RBCs) in the laminar flow regime of arterioles in a hamster window preparation and the intraluminal Po(2) profile to determine whether this variability affects the intraluminal distribution of oxygen in conditions of normal hematocrit and hemodilution. A gated image intensifier was used to visualize fluorescently labeled RBCs in tracer quantities and obtain multiple measurements of RBC radial and longitudinal positions at time intervals on the order of 5 ms within single arterioles (diameter range 40-95 microm). RBCs in the velocity range of 0.3-14 mm/s exhibit a mean coefficient of variation of velocity of 16.9 +/- 10.5% and a SD of the radial position of 1.98 +/- 0.98 microm. Both quantities were inversely related to hematocrit, and the former was significantly lowered by hemodilution. Our experimental results presented very similar values and shape compared with the intraluminal oxygen profile derived theoretically for normal hematocrit, suggesting that shear-augmented diffusion due to the measured radial displacement of RBCs did not significantly affect oxygen diffusion from blood into the arteriolar vessel wall. Po(2) profiles in the arterioles assumed an increasingly parabolic configuration with increasing levels of hemodilution.     

Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity

Responses to exchange transfusion with red blood cells (RBCs) containing methemoglobin (MetRBC) were studied in an acute isovolemic hemodiluted hamster window chamber model to determine whether oxygen content participates in the regulation of systemic and microvascular conditions during extreme hemodilution. Two isovolemic hemodilution steps were performed with 6% dextran 70 kDa (Dex70) until systemic hematocrit (Hct) was reduced to 18% (Level 2). A third-step hemodilution reduced the functional Hct to 75% of baseline by using either a plasma expander (Dex70) or blood adjusted to 18% Hct with all MetRBCs. In vivo functional capillary density (FCD), microvascular perfusion, and oxygen distribution in microvascular networks were measured by noninvasive methods. Methylene blue was administered intravenously to reduce methemoglobin (rRBC), which increased oxygen content with no change in Hct or viscosity from MetRBC. Final blood viscosities after the entire protocol were 2.1 cP for Dex70 and 2.8 cP for MetRBC (baseline, 4.2 cP). MetRBC had a greater mean arterial pressure (MAP) than did Dex70. FCD was substantially higher for MetRBC [82 (SD 6) of baseline] versus Dex70 [38 (SD 10) of baseline], and reduction of methemoglobin to oxyhemoglobin did not change FCD [84% (SD 5) of baseline]. P(O2) levels measured with palladium-meso-tetra(4-carboxyphenyl)porphyrin phosphorescence were significantly changed for Dex70 and MetRBC compared with Level 2 (Hct 18%). Reduction of methemoglobin to oxyhemoglobin partially restored P(O2) to Level 2. Wall shear rate and wall shear stress decreased in arterioles and venules for Dex70 and did not change for MetRBC or rRBC. Increased MAP and shear stress-mediated factors could be the possible mechanisms that improved perfusion flow and FCD after exchange for MetRBC. Thus the fall in systemic and microvascular conditions during extreme hemodilution with low-viscosity plasma expanders seems to be, in part, from the decrease in blood viscosity independent of the reduction in oxygen content.     

Effect of blood flow on gas transport in a pulmonary capillary

The effects of blood velocity on gas transport within the alveolar region of lungs, and on the lung diffusing capacity DL have for many years been regarded as negligible. The present work reports on a preliminary, two-dimensional investigation of CO convection-diffusion phenomenon within a pulmonary capillary. Numerical simulations were performed using realistic clinical and morphological parameter values, with discrete circular red blood cells (RBCs) moving with plasma in a single capillary. Steady-state simulations with stationary blood (RBCs and plasma) were performed to validate the model by comparison with published data. Results for RBCs moving at speeds varying from 1.0 mm/s to 10 mm/s, and for capillary hematocrit (Ht) from 5% to 55%, revealed an increase of up to 60% in DL, as compared to the stationary blood case. The increase in DL is more pronounced at low Ht (less than 25%) and high RBC speed and it seems to be caused primarily by the presence of plasma. The results also indicate that capillary blood convection affects DL not only by improving the plasma mixing in the capillary bed but also by replenishing the capillary with fresh (zero concentration) plasma, providing an additional reservoir for the consumption of CO. Our findings cast doubt on the current belief that an increase in the lung diffusing capacity of humans (for instance, during exercising), with fixed hematocrit, can only be accomplished by an increase in the lung volume effectively active in the respiration process.     

Visualization study of motion and deformation of red blood cells in a microchannel with straight,divergent and convergent sections

The size of red blood cells (RBC) is on the same order as the diameter of microvascular vessels. Therefore, blood should be regarded as a two-phase flow system of RBCs suspended in plasma rather than a continuous medium of microcirculation. It is of great physiological and pathological significance to investigate the effects of deformation and aggregation of RBCs on microcirculation. In this study, a visualization experiment was conducted to study the microcirculatory behavior of RBCs in suspension. Motion and deformation of RBCs in a microfluidic chip with straight, divergent, and convergent microchannel sections have been captured by microscope and high-speed camera. Meanwhile, deformation and movement of RBCs were investigated under different viscosity, hematocrit, and flow rate in this system. For low velocity and viscosity, RBCs behaved in their normal biconcave disc shape and their motion was found as a flipping motion: they not only deformed their shapes along the flow direction, but also rolled and rotated themselves. RBCs were also found to aggregate, forming rouleaux at very low flow rate and viscosity. However, for high velocity and viscosity, RBCs deformed obviously under the shear stress. They elongated along the flow direction and performed a tank-treading motion.     

Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cell (RBC) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBC aggregation was modeled by a Morse potential function based on depletion-mediated assumption, and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of \(15\,\upmu \hbox {m}\) diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor–ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC.     

Red Blood Cells: Centerpiece in the Evolution of the Vertebrate Circulatory System

All vertebrates except cold-water ice fish transport oxygenvia hemoglobin packaged in red blood cells (RBCs). VertebrateRBCs vary in size by thirtyfold. Differences in RBC size havebeen known for over a century, but the functional significanceof RBC size remains unknown. One hypothesis is that large RBCsare a primitive character. Agnathans have larger RBCs than domammals. However, the largest RBCs are found in urodele amphibianswhich is inconsistent with the hypothesis that large RBCs areprimitive. Another possibility is that small RBCs increase bloodoxygen transport capacity. Blood hemoglobin concentration ([Hb])and mean RBC hemoglobin concentration (MCHC) increase from Agnathato birds and mammals. However, the changes in [Hb] and MCHCdo not parallel changes in RBC size. In addition, RBC size doesnot affect blood viscosity. Thus, there is no clear link betweenRBC size and oxygen transport capacity. We hypothesize thatRBC size attends changes in capillary diameter. This hypothesisis based on the following observations. First, RBC width averages25% larger than capillary diameter which insures cell deformationduring capillary flow. Functionally, RBC deformation minimizesdiffusion limitations to gas exchange. Second, smaller capillariesare associated with increased potential for diffusive gas exchange.However, smaller capillaries result in higher resistances toblood flow which requires higher blood pressures. We proposethat the large capillary diameters and large RBCs in urodelesreflect the evolutionary development of a pulmonary vascularsupply. The large capillaries reduced systemic vascular resistancesenabling a single ventricular heart to supply blood to two vascularcircuits, systemic and pulmonary, without developing high pressureson the pulmonary side. The large RBCs preserved diffusive gasexchange efficiency in the large capillaries.     

Validation of OPS imaging for microvascular measurements during isovolumic hemodilution and low hematocrits

Orthogonal polarization spectral (OPS) imaging is a new technique that can be used to visualize the microcirculation with reflected light. It uses hemoglobin absorption to visualize the red blood cells (RBCs). Thus the method could fail at low hematocrit (Hct). The aim of this study was to validate OPS imaging for quantitative measurements of diameter and functional capillary density (FCD) under conditions of hemodilution of varying degrees to achieve a wide range of Hcts. The validation was performed in the dorsal skinfold chamber of nine awake Syrian golden hamsters. Measurements of vessel diameter and FCD were performed off-line using Cap-Image on video sequences captured using OPS imaging and standard intravital fluorescence microscopy at baseline, 85, 70, 55, and 40% of the initial Hct. For hemodilution, isovolumic exchange of blood for 6% Dextran 60 was performed. Bland-Altman plots for the vessel diameter and FCD show good agreement between the two methods for both parameters at all studied Hcts. As expected, there was a systematic bias of approximately 4 microm in the diameter measurements since the RBC column was measured and not the intravascular diameter. In conclusion, OPS imaging can be used to measure diameter and FCD at a wide range of Hcts.     

Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% (level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.     

Microvascular and capillary perfusion following glycocalyx degradation.

Systemic parameters and microvascular and capillary hemodynamics were studied in the hamster window chamber model before and after hyaluronan degradation by intravenous injection of Streptomyces hyaluronidase (100 units, 40-50 U/ml plasma). Glycocalyx permeation was estimated using fluorescent markers of different molecular size (40, 70, and 2,000 kDa), and electrical charge. Systemic parameters (blood pressure, heart rate, blood gases) and microhemodynamics (vascular tone, velocity, and blood flow) remained statistically unchanged after injection of hyaluronidase, compared with inactivated hyaluronidase. Conversely, capillary hemodynamics were drastically affected. Functional capillary density, the capillaries perfused with red blood cells (RBCs), decreased by 35%, capillary Hct of the remaining functional capillaries increased from 16 to 27%, and penetration of 70-kDa fluorescent marker increased. Furthermore, plasma-only perfused capillaries statistically increased 30 min after hyaluronidase. The decrease in functional capillary density accounted for an increased RBC flux in the remainder of the capillaries, since the same number of RBCs had to traverse a reduced number of capillaries. Flux balances showed a reduction from baseline of 11% for the RBC flux and 20% for the plasma flux after treatment. These discrepancies are within the margin of error of the techniques used and could be explained by accounting for RBC over-velocity compared with plasma. These findings suggest that the decrease in the glycocalyx leads to capillary perfusion impairments.     

Microvascular pressure and functional capillary density in extreme hemodilution with low- and high-viscosity dextran and a low-viscosity Hb-based O2 carrier

Blood losses are usually corrected initially by the restitution of volume with plasma expanders and subsequently by the restoration of oxygen-carrying capacity using either a blood transfusion or possibly, in the near future, oxygen-carrying plasma expanders. The present study was carried out to test the hypothesis that high-plasma viscosity hemodilution maintains perfused functional capillary density (FCD) by preserving capillary pressure. Microvascular pressure responses to extreme hemodilution with low- (LV) and high-viscosity (HV) plasma expanders and an exchange transfusion with a polymerized bovine cell-free Hb (PBH) solution were analyzed in the awake hamster window chamber model (n = 26). Systemic hematocrit was reduced from 50% to 11%. PBH produced a greater mean arterial blood pressure than the nonoxygen carriers. FCD was higher after a HV plasma expander (70 +/- 15%) vs. PBH (47 +/- 12%). Microvascular pressure spanning the capillary network was higher after a HV plasma expander (16-19 mmHg) compared with PBH (12-16 mmHg) and a LV plasma expander (11-14 mmHg) but lower than control (22-26 mmHg). FCD was found to be directly proportional to capillary pressure. The use of a HV plasma expander in extreme hemodilution maintained the number of perfused capillaries and tissue perfusion by comparison with a LV plasma expander due to increased mean arterial blood pressure and capillary pressure. The use of PBH increased mean arterial pressure but reduced capillary pressure due to vasoconstriction and did not maintain FCD.     

Role of erythrocyte deformability during capillary wetting

Deformability of erythrocyte was found to fundamentally alter the wetting dynamics of red blood cell (RBC) suspensions during their invasion into capillaries. Normal RBC suspensions failed to penetrate more than 1 cm into a glass capillary when the capillary radius was smaller than a critical value that is dependent on the erythrocyte concentration (about 50 microm for whole blood). In contrast, suspensions of rigidified RBCs, after cross-linking with different concentrations of glutaraldehyde or incubating with 100 ng/mL of an endotoxin, could penetrate any capillary larger than the erythrocyte dimension. The effect of RBC deformability on penetration was attributed to the enhanced shear-induced migration of normal deformable RBCs toward the capillary centreline, which imparted a higher average velocity to the RBCs than the average plasma velocity. As a result, the erythrocytes advanced into the capillary faster than the wetting meniscus, packing behind it to form a concentrated slug. This tightly packed slug had a high hydrodynamic resistance that could arrest the penetrating flow of concentrated suspensions into the small capillaries.     

Hematocrit,viscosity and velocity distributions of aggregating and non-aggregating blood in a bifurcating microchannel

Microscale blood flow is characterised by heterogeneous distributions of hematocrit, viscosity and velocity. In microvascular bifurcations, cells are unevenly distributed between the branches, and this effect can be amplified in subsequent branches depending on a number of parameters. We propose an approach to infer hematocrit profiles of human blood flowing through a bifurcating microchannel. The influence of aggregation, induced by the addition of Dextran 2000 to the samples, is also considered. Averaged values indicate plasma skimming, particularly in the presence of red blood cell (RBC) aggregation. Using an empirical model, the hematocrit profiles are used to estimate local relative viscosity distributions. Simulations are used to predict how the non-uniform viscosity influences the velocity profiles. Comparing these data to velocity profiles of RBCs measured using particle image velocimetry provides validation of the model. It is observed that aggregation blunts velocity profiles after a long straight section of channel. Downstream of the bifurcation, skewing of the velocity profiles is detected, which is enhanced by aggregation. The proposed methodology is capable of providing hitherto unreported information on important aspects of microscale blood rheology.     

Erythrocyte-associated transients in capillary PO2: an isovolemic hemodilution study in the rat spinotrapezius muscle

Mathematical simulations of oxygen delivery to tissue from capillaries that take into account the particulate nature of blood flow predict the existence of oxygen tension (Po(2)) gradients between erythrocytes (RBCs). As RBCs and plasma alternately pass an observation point, these gradients are manifested as rapid fluctuations in Po(2), also known as erythrocyte-associated transients (EATs). The impact of hemodilution on EATs and oxygen delivery at the capillary level of the microcirculation has yet to be elucidated. Therefore, in the present study, phosphorescence quenching microscopy was used to measure EATs and Po(2) in capillaries of the rat spinotrapezius muscle at the following systemic hematocrits (Hct(sys)): normal (39%) and after moderate (HES1; 27%) or severe (HES2; 15%) isovolemic hemodilution using a 6% hetastarch solution. A 532-nm laser, generating 10-micros pulses concentrated onto a 0.9-microm spot, was used to obtain plasma Po(2) values 100 times/s at points along surface capillaries of the muscle. Mean capillary Po(2) (Pc(O(2)); means +/- SE) significantly decreased between conditions (normal: 56 +/- 2 mmHg, n = 45; HES1: 47 +/- 2 mmHg, n = 62; HES2: 27 +/- 2 mmHg, n = 52, where n = capillary number). In addition, the magnitude of Po(2) transients (DeltaPo(2)) significantly decreased with hemodilution (normal: 19 +/- 1 mmHg, n = 45; HES1: 11 +/- 1 mmHg, n = 62; HES2: 6 +/- 1 mmHg, n = 52). Results suggest that the decrease in Pc(O(2)) and DeltaPo(2) with hemodilution is primarily dependent on Hct(sys) and subsequent microvascular compensations.     

Dynamical clustering of red blood cells in capillary vessels

We have modeled the dynamics of a 3-D system consisting of red blood cells (RBCs), plasma and capillary walls using a discrete-particle approach. The blood cells and capillary walls are composed of a mesh of particles interacting with harmonic forces between nearest neighbors. We employ classical mechanics to mimic the elastic properties of RBCs with a biconcave disk composed of a mesh of spring-like particles. The fluid particle method allows for modeling the plasma as a particle ensemble, where each particle represents a collective unit of fluid, which is defined by its mass, moment of inertia, translational and angular momenta. Realistic behavior of blood cells is modeled by considering RBCs and plasma flowing through capillaries of various shapes. Three types of vessels are employed: a pipe with a choking point, a curved vessel and bifurcating capillaries. There is a strong tendency to produce RBC clusters in capillaries. The choking points and other irregularities in geometry influence both the flow and RBC shapes, considerably increasing the clotting effect. We also discuss other clotting factors coming from the physical properties of blood, such as the viscosity of the plasma and the elasticity of the RBCs. Modeling has been carried out with adequate resolution by using 1 to 10 million particles. Discrete particle simulations open a new pathway for modeling the dynamics of complex, viscoelastic fluids at the microscale, where both liquid and solid phases are treated with discrete particles. Figure A snapshot from fluid particle simulation of RBCs flowing along a curved capillary. The red color corresponds to the highest velocity. We can observe aggregation of RBCs at places with the most stagnant plasma flow.     

High viscosity plasma expanders: Volume restitution fluids for lowering the transfusion trigger

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.     

Rheological study on coagulation of blood with special reference to the triggering mechanism of venous thrombus formation

A markedly reduced blood flow, an elevation of hematocrit and an increased aggregability of erythrocytes [red blood cells (RBCs)] are risk factors for venous thrombus formation (intravascular blood coagulation). However, these risk factors alone seem to be insufficient to stimulate the coagulation cascade in the absence of a primary triggering mechanism. In this paper, our rheological and biochemical studies on blood coagulation, especially focusing on procoagulant activity of RBCs, are summarized. It is shown that the intrinsic coagulation pathway is triggered by the activation of factor IX (F-IX) by RBCs. The F-IX-activating enzyme in normal human erythrocyte (RBC) membranes was purified, identified and characterized. The activation of F-IX by RBCs was enhanced by a decrease in flow shear rate and an elevation in hematocrit. The procoagulant ability of RBCs and coagulation of blood obtained from individuals with a relatively high level of hypercoagulability were enhanced compared with those for normals. The studies demonstrated a new triggering mechanism for coagulation or thrombus formation that may occur under stagnant flow conditions.     

A new red blood cell filtration device with improved time resolution and its application to the impaired RBC deformability in the diabetic ob/ob mouse

A new filtration device and blood handling technique for the assessment of RBC deformability in small blood samples is described and used to study RBC deformability in adult obese-hyperglycemic ob/ob-mice and normoglycemic controls. The new filtration device was designed to improve the time resolution during RBC incubation. Test and control RBC suspensions were directly filtered from two identical incubation chambers under a constant pressure of 1200 Pa. Nuclepore filters (3 microns) were mounted on top of several standard test tubes into which the filtrate was subsequently collected and weighed. Because the RBCs were resuspended to a very low (0.01%) hematocrit, the average number of RBCs passing each pore was less than 10. Therefore, any detectable difference must reflect the physical properties of RBCs, e.g. shape or viscoelasticity, whereas the role of white blood cells is negligible. When ob/ob-mouse RBCs were studied with the new technique they showed impaired filtrability as compared with control RBCs, both when incubated without glucose and with glucose present at the same concentration as that recorded in the RBC donating mouse.     

The physiologic reserve in oxygen carrying capacity: studies in experimental hemodilution

The mechanisms by which the body attempts to avoid tissue hypoxia when total body oxygen delivery is compromised during acute anemia are reviewed. When the hematocrit is reduced by isovolemic hemodilution the compensatory adjustments include an increase in cardiac output, redistribution of blood flow to some tissues, and an increase in the whole body oxygen extraction ratio. These responses permit whole body oxygen uptake to be maintained until the hematocrit has been lowered to about 10%. Several factors are discussed which contribute to the increase in cardiac output during acute anemia including the reduction in blood viscosity, sympathetic innervation of the heart, and increased venomotor tone. The latter has been shown to be dependent on intact aortic chemoreceptors. With respect to peripheral vascular responses, the rise in coronary and cerebral blood flows which occur following hemodilution is proportionally greater than the increase in cardiac output while the opposite is true for kidney, liver, spleen, and intestine. Skeletal muscle does not contribute to a redistribution of blood flow to more vital areas during acute anemia despite its relatively large anaerobic capacity. Overall, peripheral compensatory adjustments result in an increased oxygen extraction ratio during acute anemia which reflects a better matching of the limited oxygen supply to tissue oxygen demands. However, some areas such as muscle are relatively overperfused which limits an even more efficient utilization of the reduced oxygen supply. Studies of the response of the microcirculation and the extent to which sympathetic vascular controls are involved in peripheral blood flow regulation are necessary to further appreciate the complex pattern of physiological responses which help ensure survival of the organism during acute anemia.