Predicting optimal hematocrit in silico

Optimal hematocrit $H_o$ maximizes oxygen transport. In healthy humans, the average hematocrit $H$ is in the range of 40-45$\%$, but it can significantly change in blood pathologies such as severe anemia (low $H$) and polycythemia (high $H$). Whether the hematocrit level in humans corresponds to the optimal one is a long standing physiological question. Here, using numerical simulations with the Lattice Boltzmann method and two mechanical models of the red blood cell (RBC) we predict the optimal hematocrit, and explore how altering the mechanical properties of RBCs affects $H_o$. We develop a simplified analytical theory that accounts for results obtained from numerical simulations and provides insight into the physical mechanisms determining $H_o$. Our numerical and analytical models can easily be modified to incorporate a wide range of mechanical properties of RBCs as well as other soft particles thereby providing means for the rational design of blood substitutes. Our work lays the foundations for systematic theoretical study of the optimal hematocrit and its link with pathological RBCs associated with various diseases (e.g. sickle cell anemia, diabetes mellitus, malaria, elliptocytosis)

A novel, nondestructive, dried blood spot-based hematocrit prediction method using noncontact diffuse reflectance spectroscopy

Dried blood spot (DBS) sampling is recognized as a valuable alternative sampling strategy both in research and in clinical routine. Although many advantages are associated with DBS sampling, its more widespread use is hampered by several issues, of which the hematocrit effect on DBS-based quantitation remains undoubtedly the most widely discussed one. Previously, we developed a method to derive the approximate hematocrit from a nonvolumetrically applied DBS based on its potassium content. Although this method yielded good results and was straightforward to perform, it was also destructive and required sample preparation. Therefore, we now developed a nondestructive method which allows to predict the hematocrit of a DBS based on its hemoglobin content, measured via noncontact diffuse reflectance spectroscopy. The developed method was thoroughly validated. A linear calibration curve was established after log/log transformation. The bias, intraday and interday imprecision of quality controls at three hematocrit levels and at the lower and upper limit of quantitation (0.20 and 0.67, respectively) were less than 11%. In addition, the influence of storage and the volume spotted was evaluated, as well as DBS homogeneity. Application of the method to venous DBSs prepared from whole blood patient samples (n = 233) revealed a good correlation between the actual and the predicted hematocrit. Limits of agreement obtained after Bland and Altman analysis were -0.076 and. +0.018. Incurred sample reanalysis demonstrated good method reproducibility. In conclusion, mere scanning of a DBS suffices to derive its approximate hematocrit, one of the most important variables in DBS analysis

7Li NMR of Normal Human Erythrocytes

Lithium has been known to be an effective medication for people with bipolar disorder. The mechanisms of action of lithium in the brain is not very well understood. NMR spectroscopy and imaging are effective both in determining lithium levels in tissue and brain. We have monitored lithium levels in red blood cells. We have been able to separate intra- and extracellular compartments of lithium using shift reagents, thereby obtaining T^1 \u27s of both the compartments. Lithium uptake as a function of hematocrit was monitored weekly over a 3 week period. The time constant of 50 mM lithium uptake at 25°C and 85% hematocrit was found to be 16.5 hrs. The time constant of 1.8 mM lithium uptake at 37 °C and 45% hematocrit was found to be 11.6 hrs. Experiments on the visibility of the quadrupolar nuclei indicate that it is only 74-90% visible and the visibility decreased with decreasing concentrations

A New Approach to Model Confined Suspensions Flows in Complex Networks: Application to Blood Flow

The modeling of blood flows confined in micro-channels or micro-capillary beds depends on the interactions between the cell-phase, plasma and the complex geometry of the network. In the case of capillaries or channels having a high aspect ratio (their longitudinal size is much larger than their transverse one), this modeling is much simplified from the use of a continuous description of fluid viscosity as previously proposed in the literature. Phase separation or plasma skimming effect is a supplementary mechanism responsible for the relative distribution of the red blood cell’s volume density in each branch of a given bifur- cation. Different models have already been proposed to connect this effect to the various hydrodynamics and geometrical parameters at each bifurcation. We discuss the advantages and drawbacks of these models and compare them to an alternative approach for modeling phase distribution in complex channels networks. The main novelty of this new formulation is to show that albeit all the previous approaches seek for a local origin of the phase segre- gation phenomenon, it can arise from a global non-local and nonlinear structuration of the flow inside the network. This new approach describes how elementary conservation laws are sufficient principles (rather than the complex arametric models previously proposed) to provide non local phase separation. Spatial variations of the hematocrit field thus result from the topological complexity of the network as well as nonlinearities arising from solving a new free boundary problem associated with the flux and mass conservation. This network model approach could apply to model blood flow distribution either on artificial micro-models, micro-fluidic networks, or realistic reconstruction of biological micro-vascular networks

Functional optimization of the arterial network

We build an evolutionary scenario that explains how some crucial physiological constraints in the arterial network of mammals - i.e. hematocrit, vessels diameters and arterial pressure drops - could have been selected by evolution. We propose that the arterial network evolved while being constrained by its function as an organ. To support this hypothesis, we focus our study on one of the main function of blood network: oxygen supply to the organs. We consider an idealized organ with a given oxygen need and we optimize blood network geometry and hematocrit with the constraint that it must fulfill the organ oxygen need. Our model accounts for the non-Newtonian behavior of blood, its maintenance cost and F\aa hr\ae us effects (decrease in average concentration of red blood cells as the vessel diameters decrease). We show that the mean shear rates (relative velocities of fluid layers) in the tree vessels follow a scaling law related to the multi-scale property of the tree network, and we show that this scaling law drives the behavior of the optimal hematocrit in the tree. We apply our scenario to physiological data and reach results fully compatible with the physiology: we found an optimal hematocrit of 0.43 and an optimal ratio for diameter decrease of about 0.79. Moreover our results show that pressure drops in the arterial network should be regulated in order for oxygen supply to remain optimal, suggesting that the amplitude of the arterial pressure drop may have co-evolved with oxygen needs.Comment: Shorter version, misspelling correctio

A design principle for vascular beds: the effects of complex blood rheology

We propose a design principle that extends Murray's original optimization principle for vascular architecture to account for complex blood rheology. Minimization of an energy dissipation function enables us to determine how rheology affects the morphology of simple branching networks. The behavior of various physical quantities associated with the networks, such as the wall shear stress and the flow velocity, is also determined. Our results are shown to be qualitatively and quantitatively compatible with independent experimental observations and simulations

Estimating plasma volume in neonatal Holstein calves fed one or two feedings of a lacteal-based colostrum replacer using Evans blue dye and hematocrit values at various time points.

Twenty-eight Holstein calves were blocked by birth date and randomly assigned to one of two treatments to investigate the effect of colostrum replacer (CR) feeding regimen on plasma volume (PV). Treatments were: 1) one feeding of CR (C1; 3L of reconstituted CR 675 g of powder providing 184.5 g of IgG at birth) or 2) two feedings of CR (C2; 2L of reconstituted CR at birth and 1 L of reconstituted CR at six h). By 6 h of age, all calves had received 3L of CR providing 184.5 g of IgG. Plasma volume was estimated at six, 12, 18, and 24 h after birth using Evans blue dye (EBD). No treatment effects were noted at any time points (P \u3e 0.05). Mean PV for all calves regardless of treatment at six, 12, 18, and 24 h were 78.6, 89.2, 83.9, and 90.7 mL kg-1 of BW, respectively. Plasma volume was correlated with hematocrit (HCT), initial HCT, and treatment. Hematocrit was correlated with PV, initial HCT, and body weight. Hematocrit for six, 12, 18 and 24 h after birth can be predicted with an initial precolostral HCT determination