Function Of Hematocrit Research Articles

Computational modeling of hemodynamics and risk of thrombosis in the left atrial appendage using patient-specific blood viscosity and boundary conditions at the mitral valve.

Hemodynamics play a vital role for the risk of thrombosis in the left atrial appendage (LAA) and left atrium (LA) for patients with atrial fibrillation. Accurate prediction of hemodynamics in the LA can provide important guidance for assessing the risk of thrombosis in the LAA. Patient specificity is a crucial factor in representing the true hemodynamic fields. In this study, we investigated the effects of blood rheology (as a function of hematocrit and shear rate), as well as patient-specific mitral valve (MV) boundary conditions (MV area and velocity profiles measured by ultrasound) on the hemodynamics and thrombosis potential of the LAA. Four scenarios were setup with different degrees of patient specificity. Though using a constant blood viscosity can classify the thrombus and non-thrombus patients for all the hemodynamic indicators, the risk of thrombosis was underestimated for all patients compared with patient-specific viscosities. The results with least patient specificities showed that patients prone to thrombosis predicted by three hemodynamic indicators were inconsistent with clinical observations. Moreover, though patients had the same MV inlet flow rate, different MV models lead to different trends in the risk of thrombosis in different patients. We also found that endothelial cell activation potential and relative residence time can effectively distinguish thrombus and non-thrombus patients for all the scenarios, relatively insensitive to patient specificities. Overall, the findings of this study provide useful insights on patients-specific hemodynamic simulations of the LA.

A General Model to Calculate the Spin-Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions.

Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects. To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2 , PO2 , and B0 under both normal physiological and hyperoxic conditions. Mathematical modeling. One hundred and twenty-six published values of R1 from phantoms and animal models. 5-8.45 T. We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO2 , and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2 , and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2 > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2 ), and Bland-Altman analysis. The effect of volume fraction constants and was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2 , and PO2 of the literature data points. Bland-Altman, AIC, MSE, coefficient of determination (R2 ), SD. The model estimates agreed well with the literature values of R1 of blood (R2 =0.93, MSE=0.0013 s-2 ), and its performance was consistent across the range of parameters: B0=1.5-8.45 T, SO2 =0.40-1, PO2 =30-700 mmHg. Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments. 3 TECHNICAL EFFICACY: Stage 1.

The effect of anemia severity on postoperative morbidity among patients undergoing laparoscopic hysterectomy for benign indications.

One-third of non-pregnant women worldwide are anemic.1 Anemia is a known independent risk factor for postoperative morbidity.2 Given that the vast majority of hysterectomies are not performed in the emergency setting, we designed this study to evaluate the effect of preoperative anemia on postoperative morbidity following laparoscopic hysterectomy performed for benign indications. Our main goal is to encourage surgeons to use anemia-corrective measures before surgery when feasible. Retrospective cohort study of 98813 patients who underwent a laparoscopic hysterectomy between 2005 and 2016 for benign indications identified through the American College of Surgeons National Surgical Quality Improvement Program. Anemia was examined as a function of hematocrit and was analyzed as an ordinal variable stratified by anemia severity as mild, moderate or severe. Associations between preoperative anemia and patient demographics, preoperative comorbidities and postoperative outcomes were evaluated using univariate analyses. Multivariable logistic regression models were used to identify independent associations between hematocrit level and postoperative outcomes after adjusting for confounding covariates. At the multivariable logistic regression level, anemia severity was analyzed using hematocrit as a continuous variable to assess the independent association between each 5% decrease in hematocrit level and several postoperative morbidities. Of the 98813 patients who met our inclusion and exclusion criteria, 19.5% were anemic. A lower preoperative hematocrit was associated with higher body mass index, younger age, Black or African American race, longer operative times, and multiple other medical comorbidities. After appropriate regression modeling, anemia was identified as an independent risk factor for extended length of stay, readmission and composite morbidity after surgery. Preoperative anemia is common among patients undergoing laparoscopic hysterectomy. Preoperative anemia increases patients' risk for multiple postoperative comorbidities. Given that most hysterectomies are performed in the elective setting, gynecologic surgeons should consider the use of anemia-corrective measures to minimize postoperative morbidity.

Seeking the optimal hematocrit: May hemorheological modelling provide a solution?

Hematocrit increases during exercise and is usually decreased after regular training. However the interpretation of these facts is ambiguous since hematocrit is both a determinant of oxygen supply and the major determinant of blood viscosity. Classically hematocrit was assumed to impair blood flow, but it has been evidenced to exert a biphasic effect on it. In order to cope with these two apparently opposite effects of hematocrit, hemorheologists have proposed the concept hematocrit/viscosity ratio (h/η). This h/η ratio is related to tissue oxygenation in vascular diseases (eg, POAD) but not in healthy subjects. h/η displays a bell-shaped curve as a function of hematocrit and the hematocrit value corresponding to the maximal h/η can be assumed to be a theoretically optimal hematocrit. We propose to analyse exercise-related alterations in hematocrit according to this theoretical approach, viscosity at high shear rate being reconstructed with Quemada's equation from actual plasma viscosity and red cell rigidity at various hematocrit levels. While theoretical and actual h/η are fairly correlated in athletes both before and after exercise, actual hematocrit is lower at rest and higher after exercise compared to the theoretical one. The main statistic correlate of these discrepancies between actual and predicted hematocrit is red cell rigidity. Submaximal exercise acutely decreases the h/η ratio (despite increasing both hematocrit and viscosity). This change is well predicted by the model and there is a strong correlation between predicted and actual h/η ratio. Endurance training tends to increase h/η and to reduce the discrepancy between predicted and actual hematocrit. Accordingly trained athletes have a higher h/η (both model-predicted and actual) than sedentary subjects, and a lower hematocrit, this lowering being rather correlated to training volume than to fitness improvement. On the whole, this approach suggests that homeostatic "viscoregulation" in athletes results in a fine tuning of h/η which seems to be a closely regulated parameter. Hematocrit alterations in this context are an adaptation involved in this regulation.

Differences in Peak VO2 Among Healthy Andean Highlanders and Males with Chronic Mountain Sickness Before and After Isovolemic Hemodilution at 4350m

Excessive erythrocytosis is the hallmark of Chronic Mountain Sickness (CMS), a maladaptive clinical syndrome common in Andeans that is thought to negatively impact oxygen transport and exercise capacity. We performed cardiopulmonary exercise testing at 4350m in both healthy males (controls) and those with CMS pre‐ and post‐isovolemic hemodilution (n = 8 controls, n = 6 CMS) to determine whether they differed in exercise capacity as a function of hematocrit (Hct). Hct differed significantly between control (Hct=51.6±4.0) and pre‐hemodilution CMS subjects and between pre‐ and post‐hemodilution (Hct=66.7±4.1, 53.2±1.8, respectively; all p<0.0005), and Hct showed a negative trend with exercise capacity in CMS subjects. Anaerobic threshold was lower in CMS subjects compared to controls (p<0.01) but normalized after hemodilution. While peak VO2/kg was similar pre‐ and post‐hemodilution in CMS subjects, it was significantly different between control and CMS subjects with or without hemodilution (p<0.05). Cardiac output (QT/kg) during maximal exercise was lower in pre‐ and post‐hemodilution CMS compared to controls (p<0.02) and was relatively lower in pre‐ versus post‐hemodilution CMS subjects (p<0.05). The slopes of the QT‐VO2 relationship indicate that decreased QT response to exercise in CMS subjects is partially normalized post hemodilution (p<0.04), while the intercept is not statistically different. While QT is reduced in CMS and can be partially recovered by hemodilution, VO2 max did not increase in CMS individuals post hemodilution, suggesting this reduction of Hct does not influence exercise capacity. How the differences between CMS and non‐CMS individuals relate to other components of oxygen transport and the presence and absence of adaptive genetic factors remains to be determined.Support or Funding InformationThis study was supported by an NIH NRSA Individual Postdoctoral Fellowship (Parent F32) to ECH (F32HL131218), a Wellcome Trust PHTM grant (107544/Z/15/Z) to FCV, and an NIH R00HL118215 and American Physiological Society Giles F. Filley Memorial Award to TSS.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood.

We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO2 ) from measurements of its T1 and T2 relaxation times. Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO2 in terms of R1 and R2 . Resulting solutions for Hct and sO2 are the roots of cubic polynomials. Feasibility of the method was established by comparison of Hct and sO2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T1 , T2 measurement uncertainty on precision of Hct and sO2 estimates. Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO2 estimates. Results demonstrate accurate quantification of Hct and sO2 from T1 and T2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med 78:2352-2359, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

One-year follow-up of blood viscosity factors and hematocrit/viscosity ratio inelite soccer players.

We investigated to what extent aprediction of the 'ideal' hematocrit based on individual hemorheological profile with an equation of viscosity is relevant in trained athletes, and how the agreement between theoretical and actual values is modified by changes in training volume and performance. Elite soccer players (national level: 18-32yr, weight 61-83 kg, body mass index 20.9-25.8 kg/m2) were seen twice at one year interval. Hemorheologic parameters were measured with the MT90 viscometer and the Myrenne aggregometer the theoretical bell-shaped curve of hematocrit/viscosity ratio as afunction of hematocrit was reconstructed with Quemada's equation using actual plasma viscosity and red cell rigidity to predict hematocrit/viscosity at various hematocrit levels. RBC aggregation is correlated at baseline with fat mass (M1 = 0.552 p < 0.02) and changes in aggregation are related to changes in fat mass (M = 0.652, p < 0.05; M1 = 0.647, p < 0.05). Predicted and actual hematocrit are correlated (r = 0.644, p < 0.05) but exhibit discrepancies (mean difference -1% range [3.24 to 1.24]) and those discrepancies are inversely correlated to the level of predicted hematocrit (r = -0.912, p < 0.01), to systolic blood pressure (r = -0.626, p < 0.05), and to the overtraining score (r = -0.693, p < 0.05). After one year changes in hematocrit are aclose reflect of the change in training volume (r = -0.877, p < 0.01) but are not correlated to fitness changes. Therefore in these athletes i) systemic hematocrit is close to its predicted 'ideal value", suggesting the accuracy of the prediction; ii) red cell aggregation is correlated to fat mass even in nonobese subjects; iii) hematocrit is lower than predicted by the model when markers of sympathetic tone (systolic blood pressure, overtraining score) are increased; iv) weekly training volume appears the main determinant of the reduction of hematocrit.

Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities

Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R2) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R2CPMG) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τcp). R2CPMG in lysed cells showed a small τcp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τcp. This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τcp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R2CPMG, and the intercept R20blood at infinitely short τcp was determined. The R20blood values at different hematocrit and the R2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r2Hb) and albumin (r2Alb) in plasma. The r2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin proximity to the erythrocyte membrane. However, we cannot exclude that this is a consequence of the simple tangential model used to remove relaxation contributions from exchange and diffusion. The extensive data set presented should be useful for future theory development for the transverse relaxation of blood.

Prediction of anomalous blood viscosity in confined shear flow.

Red blood cells play a major role in body metabolism by supplying oxygen from the microvasculature to different organs and tissues. Understanding blood flow properties in microcirculation is an essential step towards elucidating fundamental and practical issues. Numerical simulations of a blood model under a confined linear shear flow reveal that confinement markedly modifies the properties of blood flow. A nontrivial spatiotemporal organization of blood elements is shown to trigger hitherto unrevealed flow properties regarding the viscosity η, namely ample oscillations of its normalized value [η] = (η-η(0))/(η(0)ϕ) as a function of hematocrit ϕ (η(0) = solvent viscosity). A scaling law for the viscosity as a function of hematocrit and confinement is proposed. This finding can contribute to the conception of new strategies to efficiently detect blood disorders, via in vitro diagnosis based on confined blood rheology. It also constitutes a contribution for a fundamental understanding of rheology of confined complex fluids.

Anticoagulant Therapy Overview

1. George A. Fritsma, MS MT (ASCP)[⇑][1] 1. The Fritsma Factor, Your Interactive Hemostasis ResourceSM, Fritsma & Fritsma LLC, Birmingham, AL 1. Address for Correspondence: George A. Fritsma MS MT (ASCP), The Fritsma Factor, Your Interactive Hemostasis ResourceSM, Fritsma & Fritsma LLC, 153 Redwood Drive, Birmingham, AL 35173, 205-655-0687, George{at}fritsmafactor.com. 1. Recount the history of heparin, Coumadin, and hirudin 2. Summarize the function of the anti-Xa drugs, vitamin K antagonists, and direct thrombin inhibitors. 3. List two oral anticoagulants that have been cleared by the US FDA since 2009. Anticoagulants do not thin the blood, even though we call them “blood thinners.”1 Blood viscosity is a function of hematocrit and, in leukemia, white blood cell burden, but not plasma protein concentration or enzyme activity. Although thrombolytic “clotbusters” like tissue plasminogen activator (TPA) or streptokinase can dissolve clots, anticoagulants cannot, another popular misconception. Anticoagulants can only prevent thrombus formation or extension by reducing plasma thrombin activity, the basis for their effectiveness. Though this may seem like a limitation, anticoagulants save many lives and promote recovery following a thrombotic (clotting) event.2 Anticoagulant treatment is either prophylactic or therapeutic. Prophylactic anticoagulation includes the prevention of ischemic stroke in people with chronic atrial fibrillation or artificial heart valves, or the prevention of venous thromboembolic (VTE) disease in the form of deep venous thrombosis (DVT, clots in major leg veins) or pulmonary emboli (PE, clots in lung vasculature), subsequent to orthopedic surgery, neurosurgery, or during a complicated pregnancy.3 Therapeutic anticoagulation, which usually implies higher doses than prophylactic anticoagulation, is used in patients with current VTE disease or those with coronary artery disease (CAD) complicated by cardiac insufficiency.4 Anticoagulants are a subset of a family of drugs called antithrombotics, which include the oral antiplatelet drugs such as aspirin and clopidogrel (Plavix); the intravenous antiplatelet membrane glycoprotein receptor drugs, abciximab, eptifibatide, and tirofiban; and the thrombolytics. This series does not address the antiplatelet drugs or the thrombolytics. In this series we first address the anti-Xa anticoagulants, heparin and its analogues; next, the historical mainstay Coumadin, our… ABBREVIATIONS: APTT or PTT-activated partial thromboplastin time; CAD - coronary artery disease; DTI - direct thrombin inhibitor; DVT - deep venous thrombosis; FDA - US Food and Drug Administration; HIT-heparin-induced thrombocytopenia with thrombosis; INR - international normalized ratio; LMWH - low molecular weight heparin; PE - pulmonary embolism; PT - prothrombin time; RI - reference interval; RUO - research use only; TPA - tissue plasminogen activator; UFH - unfractionated heparin; VKORC - vitamin K epoxide reductase; VKA - vitamin K antagonist; VTE - venous thromboembolism. 1. Recount the history of heparin, Coumadin, and hirudin 2. Summarize the function of the anti-Xa drugs, vitamin K antagonists, and direct thrombin inhibitors. 3. List two oral anticoagulants that have been cleared by the US FDA since 2009. [1]: #corresp-1

Optimal hematocrit: a Procrustean bed for maximum oxygen transport rate?

physiological systems are characterized by multiple interdependent components that collectively subserve various processes and functions. In seeking better understanding of the performance of such complex systems, we must identify and evaluate alternative ways and operating schemes, comparing their

A computational model of hemodynamic parameters in cortical capillary networks

The analysis of hemodynamic parameters and functional reactivity of cerebral capillaries is still controversial. To assess the hemodynamic parameters in the cortical capillary network, a generic model was created using 2D voronoi tessellation in which each edge represents a capillary segment. This method is capable of creating an appropriate generic model of cerebral capillary network relating to each part of the brain cortex because the geometric model is able to vary the capillary density. The modeling presented here is based on morphometric parameters extracted from physiological data of the human cortex. The pertinent hemodynamic parameters were obtained by numerical simulation based on effective blood viscosity as a function of hematocrit and microvessel diameter, phase separation and plasma skimming effects. The hemodynamic parameters of capillary networks with two different densities (consistent with the variation of the morphometric data in the human cortical capillary network) were analyzed. The results show pertinent hemodynamic parameters for each model. The heterogeneity (coefficient variation) and the mean value of hematocrits, flow rates and velocities of the both network models were specified. The distributions of blood flow throughout the both models seem to confirm the hypothesis in which all capillaries in a cortical network are recruited at rest (normal condition). The results also demonstrate a discrepancy of the network resistance between two models, which are derived from the difference in the number density of capillary segments between the models.

Pulsatile flow in a coronary artery using multiphase kinetic theory

Pulsatile flow in a model of a right coronary artery (RCA) was previously modeled as a single-phase fluid and as a two-phase fluid using experimental rheological data for blood as a function of hematocrit and shear rate. Here we present a multiphase kinetic theory model which has been shown to compute correctly the viscosity of red blood cells (RBCs) and their migration away from vessel walls: the Fahraeus–Lindqvist effect. The computed RBC viscosity decreases with shear rate and vessel size, consistent with measurements. The pulsatile computations were performed using a typical cardiac waveform until a limit cycle was well established. The RBC volume fractions, shear stresses, shear stress gradients, granular temperatures, viscosities, and phase velocities varied with time and position during each cardiac cycle. Steady-state computations were also performed and were found to compare well with time-averaged transient results. The wall shear stress and wall shear stress gradients (both spatial and temporal) were found to be highest on the inside area of maximum curvature. Potential atherosclerosis sites are identified using these computational results.

Ultrasonic backscatter from rat blood in aggregating media under in vitro rotational flow

Ultrasonic backscatter from flowing and static rat red blood cells (RBCs) in autologous plasma and in 360 kDa polyvinylpyrrolidone (PVP 360) solution was measured as a function of hematocrit. The flow speed was varied by a stirring magnet in a cylindrical chamber. The radio-frequency (RF) signals backscattered by RBC samples were measured over 5 min in a pulse-echo setup with a 5 MHz focused transducer. Although the intact rat blood has poor RBC aggregability, RBC aggregation of rat blood was enhanced by replacing its plasma with a higher molecular weight polymer solution. The experimental results showed that the nonlinear relationship between hematocrit and ultrasonic backscatter from rat RBCs in plasma and aggregating media is affected by flow speed, which may provide a unified insight into hematocrit dependence of RBC aggregation under flowing and static conditions.

Predicted influence of sample hematocrit on injected mass of internal standard in mass spectrometry assays utilizing simple protein precipitation for sample preparation

The injected mass of internal standard is often monitored in mass spectrometry assays to flag aberrant specimen processing. When simple protein precipitation is used for sample preparation, the protein volume (solids fraction) of the specimen is in principle a variable affecting the final concentration of the internal standard in the liquid phase. We examined the predicted extent of this variation for an example of protein precipitation for sample preparation used in a mass spectrometry assay for immunosuppressants in whole blood. Liquid and solid mass fractions of samples with hematocrit ranging from 15% to 60% were measured after protein precipitation of samples using a whole blood/precipitating reagent ratio of 1:4. Relative supernatant volumes as a function of hematocrit were determined. Liquid volume variation was consistent with a predicted variation in the internal standard concentration of only approximately +/-1% across this hematocrit range. Data were in close agreement with calculations based simply on protein density and concentration. Hematocrit affects the injected mass of internal standard in assays that utilize protein precipitation for sample preparation, due to predictable variation in solids and liquid fractions. The effect is small, however, compared to the typical variation observed for injected mass of internal standard.

Noninvasive Average Flow Estimation for an Implantable Rotary Blood Pump: A New Algorithm Incorporating the Role of Blood Viscosity

The effect of blood hematocrit (HCT) on a noninvasive flow estimation algorithm was examined in a centrifugal implantable rotary blood pump (iRBP) used for ventricular assistance. An average flow estimator, based on three parameters, input electrical power, pump speed, and HCT, was developed. Data were collected in a mock loop under steady flow conditions for a variety of pump operating points and for various HCT levels. Analysis was performed using three-dimensional polynomial surfaces to fit the collected data for each different HCT level. The polynomial coefficients of the surfaces were then analyzed as a function of HCT. Linear correlations between estimated and measured pump flow over a flow range from 1.0 to 7.5 L/min resulted in a slope of 1.024 L/min (R2=0.9805). Early patient data tested against the estimator have shown promising consistency, suggesting that consideration of HCT can improve the accuracy of existing flow estimation algorithms.

Characterization of Blood Properties from Coagulating Blood of Different Hematocrits Using Ultrasonic Backscatter and Attenuation

The influence of hematocrit on the change of blood properties during coagulating was extensively investigated using ultrasonic integrated backscatter and attenuation. Measurements were performed with porcine blood at hematocrits ranging from 25 to 55% using a 10 MHz transducer. Results showed that both integrated backscatter and attenuation are able to sensitively differentiate various stages of blood properties during coagulating. The slopes of integrated backscatter (Sr, dB/S) and attenuation (αr, dB·cm-1·MHz-1·mS-1) are increased relative to hematocrit. The best fits for Sr and αr as a function of hematocrit (H) equal to Sr=0.0357+1.62e-0.108H and αr=0.0281+0.003H, respectively. Variations of clotting time (Ts) and reaction time (Tα), estimated respectively from ultrasonic integrated backscatter and attenuation, associated with clot formation are also increased with hematocrit. This study demonstrates that blood hematocrit is a substantial factor affecting viscosity and backscattering properties of blood during coagulation capable of being discerned by ultrasonic backscattering and attenuation.

Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation

The reaction rate between nitric oxide and intraerythrocytic hemoglobin plays a major role in nitric oxide bioavailability and modulates homeostatic vascular function. It has previously been demonstrated that the encapsulation of hemoglobin in red blood cells restricts its ability to scavenge nitric oxide. This effect has been attributed to either factors intrinsic to the red blood cell such as a physical membrane barrier or factors external to the red blood cell such as the formation of an unstirred layer around the cell. We have performed measurements of the uptake rate of nitric oxide by red blood cells under oxygenated and deoxygenated conditions at different hematocrit percentages. Our studies include stopped-flow measurements where both the unstirred layer and physical barrier potentially participate, as well as competition experiments where the potential contribution of the unstirred layer is limited. We find that deoxygenated erythrocytes scavenge nitric oxide faster than oxygenated cells and that the rate of nitric oxide scavenging for oxygenated red blood cells increases as the hematocrit is raised from 15% to 50%. Our results 1) confirm the critical biological phenomenon that hemoglobin compartmentalization within the erythrocyte reduces reaction rates with nitric oxide, 2) show that extra-erythocytic diffusional barriers mediate most of this effect, and 3) provide novel evidence that an oxygen-dependent intrinsic property of the red blood cell contributes to this barrier activity, albeit to a lesser extent. These observations may have important physiological implications within the microvasculature and for pathophysiological disruption of nitric oxide homeostasis in diseases.

Viscoelasticity of Pediatric Blood and its Implications for the Testing of a Pulsatile Pediatric Blood Pump

Red blood cell hematocrit, aggregation and deformability, and plasma protein concentration influence the viscosity and elasticity of whole blood. These parameters affect the flow properties, especially at low shear rates (< 50 s(-1)). In particular, we have previously shown that the viscoelasticity of fluid affects the inlet filling characteristics and regions of flow separation in small pulsatile blood pumps. Although the viscosity of pediatric blood has been thoroughly studied, its elasticity has not been previously measured. Here we present the viscosity and elasticity of pediatric blood against shear rate for hematocrits from 19-56, measured using an oscillatory rheometer. There is little effect of patient age on blood viscoelasticity. A statistical analysis showed that when compared at constant hematocrit, blood from adult and pediatric patients had similar viscoelastic properties. We present blood analog solutions, as a function of hematocrit, constructed on the basis of the pediatric measurements. Flow field results for viscoelastic analogs of 20, 40 and 60% hematocrit and a Newtonian analog will be compared in the initial, in vitro testing of the Penn State pediatric blood pump, to determine the importance of incorporating a viscoelastic analog into the desigh interaction.

Surface-Modified Mesoporous Ceramics as Delivery Vehicle for Haemoglobin

Aquasomes, a new drug delivery system comprised of surface-modified nanocrystalline ceramic carbohydrate composites, was developed to serve as haemoglobin carrier for oxygen delivery. The hydroxy-apatite ceramic core was prepared by coprecipitation and self-precipitation and coated with various sugars like cellobiose, maltose, sucrose, and trehalose. The effect of drying methods, i.e., air drying, vacuum drying, and lyophilization, on the degree of binding was studied by concanavalin-induced aggregation method. Haemoglobin was adsorbed over the sugar-coated ceramics, and percent loading was estimated by benzidine method. The adsorption of sugars on calcium hydro-apatite powder and haemoglobin adsorption on sugar-adsorbed ceramic followed both Freundlich and Langmuir isotherm. The haemoglobin aquasome formulations (equivalent to 7.5% Hb) were suspended in a phosphate buffer containing 7.5% w/v albumin and 0.01% w/v lecithin, and they were evaluated for oxygen-carrying capacity, which was found to be similar to fresh blood. The Hill coefficients were found to be fairly good for its use as oxygen carrier. The haemoglobin aquasome formulations did not induce haemolysis of red blood cells nor alter the blood coagulation time. The haemoglobin content of the formulation remained unchanged on storage for 30 days. The haemoglobin desorption was fairly low under shear conditions, indicating good stability of formulation in biological system. During in vivo study in rats the survivals were monitored as function of hematocrit in rats receiving isovolemic exchange transfusion. Arterial blood pressure and heart rate did not change significantly in animals transfused with aquasomal suspension on 50% exchange transfusion.