Variations In Hematocrit Research Articles

Blood viscometer using capillary blood flow under disposable compliance pump

Blood viscosity is considered a promising indicator of cardiovascular disease and helps predict disease risks. However, conventional methods require two highly precise pumps to maintain consistent flow rates in co-flowing streams. In this study, a low-cost and disposable compliance pump was fabricated by inserting three components (a syringe needle, a blood-loaded syringe, and an air compliance unit [ACU]) into a three-way valve. Since the pump induces transient blood flow, accurately obtaining the transient flow rate is necessary. A correction factor was employed to improve the blood velocity obtained by microparticle image velocimetry. Air pressure inside the ACU was estimated using the ideal gas law. A discrete fluid circuit model was constructed to estimate the flow rate and pressure in a microfluidic channel. Four types of fluid physical properties (fluid resistance, fluid viscosity, time constant, and compliance coefficient) were obtained by analysing flow rate and pressure. The proposed method was employed to detect several types of suspended blood (variations in haematocrit, thermal-shocked RBCs, and RBC aggregation-enhanced blood). From the quantitative comparison, the proposed method provides better results than the previous method. Therefore, the proposed method is a promising tool for detecting biophysical variations in suspended blood.

Hemodynamic Characteristics of Tortuous Microvessels Using High-Fidelity Red Blood Cell Resolved Simulations

Introduction: Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. These vessels have unique morphology compared to straight vessels, the latter being the subject of extensive flow modeling studies over the past few decades. Three-dimensional hemodynamics in tortuous microvessels influenced by red blood cell (RBCs), however, remain largely unknown and important questions remain. Is blood viscosity influenced by vessel tortuosity? Do RBC flow dynamics cause localized hematocrit variations in tortuous vessels? How do these dynamics affect wall shear stress patterns and the near-wall cell-free layer? Previous work has connected physiological function to tortuosity1, while other recent work has shown how RBC dynamics and vessel complexity can influence hemodynamics2. Such findings drive our hypothesis that unique hemodynamic characteristics exist in tortuous microvessels compared to straight vessels. Revealing such differences and answering the above questions requires 3D RBC-resolved simulations. The objective of this work is to investigate the hemodynamic characteristics of tortuous microvessels using high-fidelity red blood cell (RBC) resolved simulations and real image data. Methods: High fidelity RBC resolved simulations were performed using a 3D immersed boundary method (IBM) based fluid dynamic solver3. A tortuous microvessel is constructed in 3D based on imaging of a rat mesenteric microvascular network post angiogenic remodeling. The diameter and length of the vessel are 20 μm and 930 μm, respectively. Simulations were performed spanning a range of physiological shear rates (SR) and overall hematocrit levels (Ht). Output simulation data is used to parametrically quantify characteristics of apparent viscosity, local hematocrit variations, time-averaged wall shear stress (TAWSS) and cell free layer (CFL) patterns due to vessel tortuosity. Data and Results: The findings show how curvature can increase apparent viscosity to different degrees based on overall Ht & SR (max 236% increase), with local variations occurring over the vessel length at sites of curvature changes (max 2.25cP change). Because of RBC flow patterns, local variations in tube hematocrit are found to occur which result in local curvature-dependent variations in the Fahraeus effect. We further characterize dependencies of the CFL and TAWSS on Ht & SR and resultant lengthwise 3D spatial variations along the vessel, and demonstrate correlation patterns between these two quantities as influenced by tortuosity. Conclusions: New findings from this work reveal significant dependency of hemodynamic parameters and spatial variations on vessel tortuosity. The results provide new information to better understand the role of vessel tortuosity in physiological and pathological processes, as well as help improve reduced-order models. NSF CBET 2309559, NIH R21HL159501, and Expanse at the San Diego Supercomputer Center per NSF Accelerate Award BIO230073. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

Effect of COVID-19 and Its Vaccine: Hematological and Immunological Study of Recovered Individuals Based on Gender

Abstract Background: The necessary urgent global response measures were implemented to contain the rapid spread of coronavirus disease 2019 (COVID-19). Vaccination has been the most effective way to combat this pandemic. Objective: The aim of the current study was to evaluate the hematological parameters and COVID-19-specific antibodies in a healthy population with different COVID-19 and vaccination backgrounds, taking gender into account. Materials and Methods: The study involved 80 healthy adults who were categorized into four groups based on their COVID-19 and vaccination status. The male and female categorization was later added to these groups. Blood samples were collected and analyzed for COVID-19-specific antibodies, IgG and IgM, and complete blood count parameters. The samples were collected in Karbala, Iraq. Results: The results showed that the IgG levels of IV and NIV subsets were higher than INV NINV subsets at P value < 0.001. No significant differences were found in white blood cell parameters except for lymphocytes, neutrophils, and their ratio between the four groups. However, when gender was taken into account, few significant differences were observed in white blood cells, lymphocytes, and neutrophils between the groups. The platelet indices showed no significant changes within the individual groups or genders. Red blood cell variables also showed no significant changes between groups, but variations in red blood cells, hematocrit, and hemoglobin were found for each gender-divided group specifically (P value < 0.001). Conclusion: The present study concludes that vaccination mimics infection. No changes were observed for most hematological parameters between the four explored subsets. However, the study revealed gender-specific responses to red blood cell counts and other related parameters, reinforcing the importance of complete blood count testing and advocating a deeper exploration into gender-specific responses, especially for patients with specific hematological conditions.

Hematological parameters vary with life history stage in the pale‐breasted thrush Turdus leucomelas

The avian life cycle is composed by a progressive sequence of life history stages (LHS). Changes in energy expenditure and exposure to stressors at different LHS require corresponding changes in behavior, physiology, and morphology. Variation in hematological parameters, such hematocrit (Hct), hemoglobin (Hb), and heterophil to lymphocyte ratio (H/L ratio), can have permissive, stimulatory, and preparative actions to help maintain homeostasis through different LHS. Few studies have examined differences in these parameters among different LHS in free‐living birds, with most of them restricted to temperate zones. We collected blood samples and measured hematological parameters every week for over a year from a population of a common resident bird species in southeastern Brazil, the pale‐breasted thrush Turdus leucomelas. Hematocrit and hemoglobin concentration were highest during the onset of the reproduction and lowest during molt. Furthermore, H/L ratios were higher at the end of the reproduction, indicating that the breeding season could be the most stressful period of the year for this population of thrushes. There was no difference between sexes for any hematological parameter at any LHS. These results show that there is a permissive physiological effect for Hct and Hb to facilitate LHS transitions and that reproduction could be the most stressful event for this species. Lastly, these results mirror those from temperate species despite distinct environmental differences between these regions.

The rheology of interactions between leukocytes, platelets and the vessel wall in thrombo-inflammation.

Leukocytes and platelets must adhere to the wall of blood vessels to carry out their protective functions in inflammation and haemostasis. Recruitment is critically dependent on rheological variables (wall shear rate and stress, red cell aggregation and haematocrit) which affect delivery to the vessel wall as well as velocities and forces experienced there. Leukocyte recruitment is efficient only up to wall shear rates of about 300s-1 and usually restricted to low-shear post-capillary venules in inflammation. Being smaller, platelets experience lower velocities and shear forces adjacent to the wall and can adhere at much higher shear rates for haemostasis in arteries. In addition, we found quite different effects of variations in haematocrit or red cell aggregation on attachment of neutrophils or platelets, which also assist their separate recruitment in venules or arteries. However, it has become increasingly evident that inflammatory and thrombotic responses may occur together, with platelets promoting the adhesion and activation of neutrophils and monocytes. Indeed, it is 30 years since we demonstrated that platelets could cause neutrophils to aggregate in suspension and, when attached to a surface, could support selectin-mediated rolling of all leukocytes. Thrombin-activated platelets could further induce neutrophil activation and immobilisation. In some conditions, platelets could bind to intact endothelial monolayers and capture neutrophils or monocytes. Subsequently, we found that extracellular vesicles released by activated platelets (PEV) fulfilled similar functions when deposited on surfaces or bound to endothelial cells. In murine models, platelets or PEV could act as bridges for monocytes in inflamed vessels. Thus, leukocytes and platelets are rheologically adapted for their separate functions, while novel thrombo-inflammatory pathways using platelets or PEV may underlie pathogenic leukocyte recruitment.

Impact of hematocrit on pulsatile blood flow in stenosed arteries: a computational study in healthy, diabetic, and anemic models

In this study, researchers aim to enhance the realism of circulatory system simulations, focusing on factors affecting flow variations, particularly in stenotic arteries of individuals with altered hematocrit levels. Through extensive data collection and varied conditions, the goal is to attain more precise and valid results. The study conducts approximate simulations to comprehensively describe the dynamic motion of pulsatile flow. Different values of inlet velocity (UDF) are introduced, considering potential arterial distortion or occlusion due to plaque deposition, along with variations in hematocrit (Hct) levels commonly observed in patients. Three distinct types of pulsatile blood flow, corresponding to diabetes (Hct 65%), healthy (Hct 45%), and anemia (Hct 25%), are studied and compared. The research illuminates that stenosis in arteries with varying hematocrit levels significantly impacts hydrodynamic features, potentially predisposing individuals to cardiovascular diseases. Through meticulous analysis, several conclusions about hemodynamic characteristics are drawn. It is observed that both velocity and wall shear stress exhibit variation along the affected artery, influenced by stenosis and changes in hematocrit levels. Notably, the highest influence on velocity and wall shear stress is observed with Hct 65%, compared to Hct 45% and Hct 25% at the moment of stenosis. These findings hold substantial practical implications for the field of cardiovascular health, providing valuable insights into blood flow behavior in stenotic arteries with diverse hematocrit levels. Ultimately, this research contributes to more effective clinical interventions.

Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids.

Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research.

Microfluidic viscometer using capillary pressure sensing

Blood viscosity is considered as a vital determinant of the efficiency of blood flow in blood-vessel networks. The coflowing method is considered as a promising technique for measuring blood viscosity. However, it requires two precise syringe pumps to supply two fluids (i.e., the reference fluid and blood), calibration in advance, and long waiting time for securing steady blood flow. To solve these problems, a single syringe pump is adopted to supply blood into a microfluidic device without requiring a reference fluid. Two key parameters—fluidic resistance and compliance coefficient—are suggested and obtained by analyzing the fluid velocities in a microfluidic channel and calculating the air pressure in the air compliance unit. Using a discrete fluidic circuit model, the pressure difference is analytically derived and utilized as the nonlinear regression formula. The two key parameters are then obtained through nonlinear regression analysis. According to experimental results, the air cavity and flow rate contribute to increasing the compliance coefficient. The fluidic resistance increases significantly at higher concentrations of glycerin solution ranging from 20% to 50%. The proposed method underestimates the values by approximately 27.5% compared with the previous method. Finally, the proposed method is adopted to detect the effects of hematocrit and red blood cell sedimentation in the driving syringe based on two vital parameters. Regarding the fluidic resistance, the normalized difference between the proposed and previous methods is less than 10%. Therefore, two key parameters can be considered as effective for quantitatively monitoring the hematocrit variation in blood flow. In conclusion, from a biomechanical perspective, the proposed method is highly promising for quantifying blood flow in a microfluidic channel.

Erythrocytosis Is Rare With Exogenous Testosterone in Gender-Affirming Hormone Therapy.

Studies have found a variable incidence of erythrocytosis among people using testosterone as part of gender-affirming hormone therapy (GAHT). To examine the effect of using exogenous testosterone as GAHT on hematocrit in a large North American cohort. We conducted a cross-sectional analysis of testosterone and hematocrit laboratory values in 6670 patients who were prescribed testosterone through Plume, a national provider of GAHT. The prevalence of erythrocytosis, the mean hematocrit at predetermined testosterone thresholds and with varying routes of testosterone administration were assessed. Among 6670 individuals, 560 (8.4%) had a hematocrit ≥50%, 182 ≥ 52% (2.7%), and 60 ≥ 54% (0.9%). There was significant variation (P < .001) in hematocrit between different clinically relevant testosterone thresholds (T < 50 vs T 50-299 vs T 300-999 vs T ≥ 1000 ng/dL) and when comparing serum testosterone in increments of 50 ng/dL within the target range for males (300-1000 ng/dL) (P < .001). Mean hematocrit ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Patients on intramuscular testosterone had a higher mean hematocrit than those on transdermal testosterone (44.96% vs 43.41%, P < .001). Both route of administration (P < .001) and testosterone level (P < .001) had statistically significant associations with hematocrit when controlling for each other. While the magnitude of change in hematocrit with serum level and route of administration of testosterone was statistically significant, the absolute levels were within the normal range, unlikely to be clinically meaningful. These findings, along with the low prevalence of erythrocytosis, should help allay concerns about the use of testosterone as GAHT.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Red Blood Cell Partitioning Using a Microfluidic Channel with Ladder Structure.

This study investigated the partitioning characteristics of red blood cells (RBCs) within capillaries, with a specific focus on ladder structures observed near the end of the capillaries. In vitro experiments were conducted using microfluidic channels with a ladder structure model comprising six bifurcating channels that exhibited an anti-parallel flow configuration. The effects of various factors, such as the parent channel width, distance between branches, and hematocrit, on RBC partitioning in bifurcating channels were evaluated. A decrease in the parent channel width resulted in an increase in the heterogeneity in the hematocrit distribution and a bias in the fractional RBC flux. Additionally, variations in the distance between branches affected the RBC distribution, with smaller distances resulting in greater heterogeneity. The bias of the RBC distribution in the microchannel cross section had a major effect on the RBC partitioning characteristics. The influence of hematocrit variations on the RBC distribution was also investigated, with lower hematocrit values leading to a more pronounced bias in the RBC distribution. Overall, this study provides valuable insights into RBC distribution characteristics in capillary networks, contributing to our understanding of the physiological mechanisms of RBC phase separation in the microcirculatory system. These findings have implications for predicting oxygen heterogeneity in tissues and could aid in the study of diseases associated with impaired microcirculation.

Evaluation of the relationship between clinical and laboratory risk factors in atherosclerosis patients with coronary slow flow: a case–control analysis

BackgroundCoronary slow flow (CSF) is an angiographic entity distinguished by the delayed filling of the epicardial coronary arteries in the lack of significant obstructive artery disease. The pathological causes are still unknown. This study aimed to elucidate the relationship between clinical and laboratory-related risk factors in atherosclerosis patients diagnosed with CSF.ResultsThe research encompassed a study group of 142 individuals, with a mean age of 52.47 ± 10.62, and a male representation of 47.7%. A thorough statistical analysis was conducted, indicating that there were no noteworthy variations in age, gender, smoking history, hematocrit, blood sugar, and HDL levels between the groups of cases and controls (P > 0.05). Subsequent analysis of the data indicated that there were significant differences in history of hypertension, LDL, and BMI measurements between the groups of subjects who were designated as cases and those who were designated as controls. Our study revealed that male gender, a history of hypertension, and BMI were identified as independent predictors of CSF (P < 0.05).ConclusionsAfter modeling regression, we were able to conclude that male gender, BMI, and history of hypertension are reliable predictors of slow coronary flow. These findings add to our growing understanding of the complex interplay between clinical and laboratory risk factors in the development and progression of CSF.

Analysis of C-reactive protein from finger stick dried blood spot to predict high risk of cardiovascular disease

C-reactive protein (CRP) is an acute-phase protein involved in inflammation. Furthermore, CRP is an important biomarker used in diagnostics to predict risk of cardiovascular disease (CVD) in addition to monitoring bacterial and viral infections. To measure plasma CRP, venipuncture is still necessitated and has to be performed by trained phlebotomists. As a solution, dried blood spots (DBS) are used for minimally invasive at-home sampling of blood and can be send to diagnostic laboratories by regular mail. In this study, we included 53 patients that presented to the outpatient clinic of the University Medical Center Utrecht. Capillary finger stick was used to spot blood on a filter paper card and allowed to dry. After extraction of DBS, CRP was analyzed on an automated high-throughput chemistry analyzer. Additional validation steps regarding stability, effect of hematocrit, precision, and limits of blank and quantitation were conducted according to corresponding Clinical and Laboratory Standards Institute standards. An excellent regression analysis of R2 (95% confidence interval) = 0.986 (0.982–0.989) was found. This enabled correct classification for high CVD risk of all 25 cases with sensitivity (95% CI) of 1.00 (1.00–1.00) and specificity (95% CI) of 0.96 (0.89–1.03) and correct diagnosis of inflammation of 12/13 cases with sensitivity (95% CI) of 0.92 (0.77–1.07) and specificity (95% CI) of 1.00 (1.00–1.00). Furthermore, CRP was found to be stable for 31 days and observed hematocrit variation amongst patients was clinically acceptable. CRP from DBS can be accurately measured on an automated high-throughput chemistry analyzer and used to diagnose inflammation and classify high CVD risk. This method enables individuals to engage in at-home sampling of blood on DBS for (tele)diagnostics, screening programs, patient follow-up, and medication management.

Factors Affecting Day-to-Day Variations in Tacrolimus Concentration among Children and Young Adults Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Tacrolimus is widely used as prophylaxis for graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (allo-HSCT). It has a narrow therapeutic index range. High tacrolimus concentrations are associated with toxicity, while low concentrations are associated with an increased risk of GVHD. Although dose adjustments based on therapeutic drug monitoring are performed, unexpected large variations in tacrolimus concentration are sometimes encountered. Thus far, the available evidence suggests that the factors affecting tacrolimus concentration are not fully understood. This study was primarily aimed at investigating the factors affecting day-to-day variations in tacrolimus concentration among children and young adults who received continuous tacrolimus infusion after allo-HSCT. The secondary objective was identifying the factors causing large variations (> 20%) in tacrolimus concentrations. This was a retrospective cohort study of 123 consecutive pediatric and young adult patients, aged < 25 years, who received continuous intravenous tacrolimus infusion after allo-HSCT at Shinshu University Hospital, Matsumoto, Japan, between January 2009 and December 2021. To compare day-to-day variations in tacrolimus concentrations without consideration of the tacrolimus dose, two consecutive days when the tacrolimus dose was not changed were selected from the first day when the tacrolimus concentration was higher than 7 ng/mL after allo-HSCT to day 28 after allo-HSCT. Subsequently, information for the following 24-h was collected in addition to the tacrolimus concentrations and hematocrit values. Tacrolimus concentration was determined using whole blood samples. Tacrolimus concentrations significantly increased in patients who received red blood cell concentrate (RCC) transfusion (p < 0.0001) and methotrexate (p = 0.0162), patients with persistent fever (p = 0.0056), and patients with a decline in fever (p = 0.0003). In contrast, tacrolimus concentrations decreased significantly in patients who received platelet concentrate (PC) transfusion (p < 0.0001), redeveloped fever (p = 0.0261), and received replaced tacrolimus administration route set (p = 0.0008). Variations in tacrolimus concentration significantly correlated with variations in hematocrit (r = 0.556, p < 0.0001). Body weight (p < 0.0001), RCC transfusion (p < 0.0001), methotrexate use (p = 0.0333), persistent fever (p = 0.0150), and decline in fever (p = 0.0073) were associated with a sharp increase in tacrolimus concentration. In contrast, body weight (p < 0.0001), PC transfusion (p = 0.0025), and replacement of the tacrolimus administration route set (p = 0.0025) were associated with a sharp decrease in tacrolimus concentration. RCC and PC transfusions, fever, methotrexate administration, and replacement of the tacrolimus administration route set were independent factors affecting day-to-day variations in tacrolimus concentration. In addition to these factors, low body weight was a risk factor for both a sharp increase and decrease in tacrolimus concentration. These findings suggest the need for better control of tacrolimus concentrations using whole blood samples.

Preserved peak exercise capacity in Andean highlanders with excessive erythrocytosis both before and after isovolumic hemodilution.

In chronic mountain sickness (CMS), increased blood oxygen (O2)-carrying capacity due to excessive erythrocytosis (EE, [Hb] ≥ 21 g/dL) could be offset, especially during exercise by both impaired cardiac output (Q̇t) and O2 diffusion limitation in lungs and muscle. We hypothesized that EE results in reduced peak V̇o2 despite increased blood O2-carrying capacity, and that isovolumic hemodilution (IVHD) improves exercise capacity. In 14 male residents of Cerro de Pasco, Peru (4,340 m), six with and eight without EE, we measured peak cycle-exercise capacity, V̇o2, Q̇t, arterial blood gas parameters, and (resting) blood volume. This was repeated for participants with EE after IVHD, reducing hematocrit by 20% (from 67% to 53%). From these data, we quantified the major O2 transport pathway components (ventilation, pulmonary alveolar-capillary diffusion, Q̇t, and blood-muscle mitochondria diffusion). Participants with EE had similar peak V̇o2, systemic O2 delivery, and O2 extraction as non-EE controls, however, with lower Q̇t and higher arterial [O2]. After IVHD, peak V̇o2 was preserved (but not enhanced), with lower O2 delivery (despite higher Q̇t) balanced by greater O2 extraction. The considerable variance in exercise capacity across the 14 individuals was explained essentially completely by differences in both pulmonary and muscle O2 diffusional conductances and not by any differences in ventilation, [Hb], nor Q̇t. In conclusion, EE does not result in lower peak V̇o2 in Andean males, and IVHD maintains, but does not enhance, exercise capacity.NEW & NOTEWORTHY Male Andean highlanders with and without excessive erythrocytosis (EE) have similar peak V̇o2 at 4,340 m, with higher arterial [O2] in EE and lower cardiac output (Q̇t), thus maintaining similar O2 delivery. Peak V̇o2 in participants with EE was unaffected by isovolumic hemodilution (hematocrit reduced from 67% to 53%), with lower O2 delivery balanced by slightly increased Q̇t and greater O2 extraction. Differences in lung and muscle diffusing capacity, and not hematocrit variation, accounted for essentially all interindividual variance in peak V̇o2.

The coronary capillary bed and its role in blood flow and oxygen delivery: A review.

The assumption that the coronary capillary blood flow is exclusively regulated by precapillary vessels is not supported by recent data. Rather, the complex coronary capillary bed has unique structural and geometric characteristics that invalidate many assumptions regarding red blood cell (RBC) transport, for example, data based on a single capillary or that increases in flow are the result of capillary recruitment. It is now recognized that all coronary capillaries are open and that their variations in flow are due to structural differences, local O2 demand and delivery, and variations in hematocrit. Recent data reveal that local mechanisms within the capillary bed regulate flow via signaling mechanisms involving RBC signaling and endothelial-associated pericytes that contract and relax in response to humoral and neural signaling. The discovery that pericytes respond to vasoactive signals (e.g., nitric oxide, phenylephrine, and adenosine) underscores the role of these cells in regulating capillary diameter and consequently RBC flux and oxygen delivery. RBCs also affect blood flow by sensing and releasing nitric oxide to facilitate relaxation of pericytes and a consequential capillary dilation. New data indicate that these signaling mechanisms allow control of blood flow in specific coronary capillaries according to their oxygen requirements. In conclusion, mechanisms in the coronary capillary bed facilitate RBC density and transit time, hematocrit, blood flow and O2 delivery, factors that decrease capillary heterogeneity. These findings have important clinical implications for myocardial ischemia and infarction, as well as other vascular diseases.

Functional implications of microvascular heterogeneity for oxygen uptake and utilization.

In the vascular system, an extensive network structure provides convective and diffusive transport of oxygen to tissue. In the microcirculation, parameters describing network structure, blood flow, and oxygen transport are highly heterogeneous. This heterogeneity can strongly affect oxygen supply and organ function, including reduced oxygen uptake in the lung and decreased oxygen delivery to tissue. The causes of heterogeneity can be classified as extrinsic or intrinsic. Extrinsic heterogeneity refers to variations in oxygen demand in the systemic circulation or oxygen supply in the lungs. Intrinsic heterogeneity refers to structural heterogeneity due to stochastic growth of blood vessels and variability in flow pathways due to geometric constraints, and resulting variations in blood flow and hematocrit. Mechanisms have evolved to compensate for heterogeneity and thereby improve oxygen uptake in the lung and delivery to tissue. These mechanisms, which involve long‐term structural adaptation and short‐term flow regulation, depend on upstream responses conducted along vessel walls, and work to redistribute flow and maintain blood and tissue oxygenation. Mathematically, the variance of a functional quantity such as oxygen delivery that depends on two or more heterogeneous variables can be reduced if one of the underlying variables is controlled by an appropriate compensatory mechanism. Ineffective regulatory mechanisms can result in poor oxygen delivery even in the presence of adequate overall tissue perfusion. Restoration of endothelial function, and specifically conducted responses, should be considered when addressing tissue hypoxemia and organ failure in clinical settings.

Daily and fasting variation in blood parameters and HL ratio in House Sparrow (Passer domesticus)

Fluctuations in food supply are frequent in nature during seasons, in different stages of annual cycle of animals, and lately, climate change has become a strong driving force that could affect food supply. An animal's capacity to resist fasting is, therefore, determined by its ability to store energy and control its allocation during periods of food restriction. Daily variations of metabolic substrates and their fluctuations during fasting are relevant to understand the acclimation to fasting. Since fasting is an ecological stressor, we investigated the daily variation of corticosterone levels in feeding and fasting in House Sparrows ( Passer domesticus (Linnaeus, 1758)), and its short-term effect on some biochemical parameters. We found daily variations in body mass, glucose, triglycerides, plasma total protein, uric acid, and corticosterone. However, we did not find diurnal variations of hematocrit and the heterophil:lymphocyte ratio (HL ratio). Moreover, we did not find sex-related differences in any parameter. Throughout fasting, we found variations of glucose, triglycerides, total protein, uric acid, HL ratio, and corticosterone. During the photophase, biochemical and physiological responses to food deprivation contributed to the efficient use of resources in this small bird. In the course of fasting period, corticosterone could be responsible for alterations of some blood parameters such as glucose.

Total Knee Arthroplasty: Superiority of Intra-Articular Tranexamic Acid Over Intravenous and Cell Salvage as Blood Sparing Strategy - A Retrospective Study.

PurposeTotal knee arthroplasty is associated with considerable perioperative hemorrhage. The decrease in hemoglobin concentration and the need for allogenic blood transfusion are related to increased morbidity and mortality. Strategies for minimizing perioperative bleeding are used, such as tranexamic acid and cell salvage. The study aimed to compare intravenous, intra-articular tranexamic acid and cell salvage protocols regarding perioperative hemoglobin variation. Secondary outcomes included blood loss; allogenic transfusions; complications and in-hospital stay.Patients and MethodsPatients submitted to unilateral total knee arthroplasty between January and December 2018 were retrospectively evaluated. After excluding 62 patients, 204 were subdivided into 3 groups according to the protocol used. Statistical analysis was performed with SPSS version 26.0. One-way ANOVA and Kruskal–Wallis tests were used. Considered a p-value of <0.05 for statistical significance.ResultsVariation of hemoglobin in the intra-articular tranexamic acid group was significantly lower than that of intravenous (p < 0.001) and cell salvage (p = 0.001) groups. Blood loss, variation of hematocrit, need for blood transfusion and in-hospital stay were also statistically significantly lower in the intra-articular tranexamic acid group. The only related complications were in the intravenous tranexamic acid group. No thromboembolic complications were identified which further solidifies the safety of tranexamic acid administration.ConclusionThis data shows superiority of the intra-articular administration of tranexamic acid over the other techniques in total knee arthroplasty. We propose this protocol as an efficient, low-risk blood-sparing strategy.