scholarly journals Red Blood Cell 2,3-Diphosphoglycerate Decreases in Response to a 30 km Time Trial Under Hypoxia in Cyclists

2021 ◽  
Vol 12 ◽  
Author(s):  
Kamila Płoszczyca ◽  
Miłosz Czuba ◽  
Małgorzata Chalimoniuk ◽  
Robert Gajda ◽  
Marcin Baranowski
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Average Power ◽  
Time Trial ◽  
Intense Exercise ◽  
Acid Base ◽  
Hypoxic Conditions ◽  
Acid Base Equilibrium ◽  
Dissociation Curves ◽  
2,3 Dpg

Red blood cell 2,3-diphosphoglycerate (2,3-DPG) is one of the factors of rightward-shifted oxygen dissociation curves and decrease of Hb-O2 affinity. The reduction of Hb-O2 affinity is beneficial to O2 unloading at the tissue level. In the current literature, there are no studies about the changes in 2,3-DPG level following acute exercise in moderate hypoxia in athletes. For this reason, the aim of this study was to analyze the effect of prolonged intense exercise under normoxic and hypoxic conditions on 2,3-DPG level in cyclists. Fourteen male trained cyclists performed a simulation of a 30 km time trial (TT) in normoxia and normobaric hypoxia (FiO2 = 16.5%, ~2,000 m). During the TT, the following variables were measured: power, blood oxygen saturation (SpO2), and heart rate (HR). Before and immediately after exercise, the blood level of 2,3-DPG and acid–base equilibrium were determined. The results showed that the mean SpO2 during TT in hypoxia was 8% lower than in normoxia. The reduction of SpO2 in hypoxia resulted in a decrease of average power by 9.6% (p < 0.001) and an increase in the 30 km TT completion time by 3.8% (p < 0.01) compared to normoxia. The exercise in hypoxia caused a significant (p < 0.001) decrease in 2,3-DPG level by 17.6%. After exercise in normoxia, a downward trend of 2,3-DPG level was also observed, but this effect was not statistically significant. The analysis also revealed that changes of acid–base balance were significantly larger (p < 0.05) after exercise in hypoxia than in normoxia. In conclusion, intense exercise in hypoxic conditions leads to a decrease in 2,3-DPG concentration, primarily due to exercise-induced acidosis.

scholarly journals Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Complete Elimination ◽  
Cell Disease ◽  
The Impact ◽  
2,3 Dpg

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.

Blood preservation. XXVIII. Galactose and maltose maintain red blood cell 2,3-DPG and ATP

Transfusion ◽  
1980 ◽  
Vol 20 (1) ◽  
pp. 110-113 ◽  
Author(s):  
RB Dawson ◽  
RT Hershey ◽  
CS Myers ◽  
TF Zuck
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Blood Preservation ◽  
2,3 Dpg

Hypoxia, Hormones, and Red Blood Cell Function in Chick Embryos

Physiology ◽  
2003 ◽  
Vol 18 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Stefanie Dragon ◽  
Rosemarie Baumann
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Adrenergic Receptor ◽  
Cell Function ◽  
Oxygen Affinity ◽  
Terminal Differentiation ◽  
Receptor Activation ◽  
Avian Embryos ◽  
Hypoxic Conditions ◽  
Hemoglobin Oxygen Affinity

The red blood cell function of avian embryos is regulated by cAMP. Adenosine A2A and β-adrenergic receptor activation during hypoxic conditions cause changes in the hemoglobin oxygen affinity and CO2 transport. Furthermore, experimental evidence suggests a general involvement of cAMP in terminal differentiation of avian erythroblasts.

scholarly journals IN VITRO INTERACTIONS BETWEEN OXYGEN AND CARBON DIOXIDE TRANSPORT IN THE BLOOD OF THE SEA LAMPREY (PETROMYZON MARINUS)

1992 ◽  
Vol 173 (1) ◽  
pp. 25-41 ◽  
Author(s):  
R. A. Ferguson ◽  
N. Sehdev ◽  
B. Bagatto ◽  
B. L. Tufts
Keyword(s):  
Carbon Dioxide ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Red Blood Cell ◽  
Whole Blood ◽  
Blood Cells ◽  
Sea Lamprey ◽  
Carbon Dioxide Transport ◽  
Dissociation Curves

In vitro experiments were carried out to examine the interactions between oxygen and carbon dioxide transport in the blood of the sea lamprey. Oxygen dissociation curves for whole blood obtained from quiescent lampreys had Hill numbers (nH) ranging from 1.52 to 1.89. The Bohr coefficient for whole blood was -0.17 when extracellular pH (pHe) was considered, but was much greater (-0.63) when red blood cell pH (pHi) was considered. The pHi was largely dependent on haemoglobin oxygen- saturation (SO2) and the pH gradient across the red blood cell membrane was often reversed when PCO2 was increased and/or SO2 was lowered. The magnitude of the increase in pHi associated with the Haldane effect ranged from 0.169 pH units at 2.9 kPa PCO2 to 0.453 pH units at a PCO2 of 0.2 kPa. Deoxygenated red blood cells had a much greater total CO2 concentration (CCO2) than oxygenated red blood cells, but the nonbicarbonate buffer value for the red blood cells was unaffected by oxygenation. Plasma CCO2 was not significantly different under oxygenated or deoxygenated conditions. Partitioning of CO2 carriage in oxygenated and deoxygenated blood supports recent in vivo observations that red blood cell CO2 carriage can account for much of the CCO2 difference between arterial and venous blood. Together, the results also suggest that oxygen and carbon dioxide transport may not be tightly coupled in the blood of these primitive vertebrates. Finally, red cell sodium concentrations were dependent on oxygen and carbon dioxide tensions in the blood, suggesting that sodium-dependent ion transport processes may contribute to the unique strategy for gas transport in sea lamprey blood.

scholarly journals Voxelotor Improves Sickle Red Blood Cell Flow Under Hypoxia in a Microfluidic Venule

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 28-29
Author(s):  
Melissa Azul ◽  
David K. Wood
Keyword(s):  
Blood Flow ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Microfluidic Device ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Hypoxic Conditions ◽  
Flow Response ◽  
Gas Layer

Introduction Sickle cell disease affects a large population both nationally and globally. The disease is characterized by the presence of sickle hemoglobin, HbS, which polymerizes the red blood cell into a stiff, sickle shape upon deoxygenation. This polymerization causes several complications, most notably, vaso-occlusion. Voxelotor (Oxbryta, Global Blood Therapeutics) is a newly FDA approved therapeutic for the treatment of sickle cell disease that, when bound to HbS, maintains the oxy-Hb state and inhibits polymerization. Previous studies have demonstrated voxelotor's ability to improve the deformability of the sickle red blood cell (sRBC) via micropippeting and reduce viscosity under hypoxia through using a viscosmeter(Dufu et al, 2018), however its effect under dynamic flow conditions has yet to be explored. Microfluidic devices have served as useful tools to study sickle cell disease, allowing investigation under physiologic conditions of the rheological properties of the sRBC. In this experimental study we aim to examine voxelotor's effect on rheological properties of blood using a microfluidic platform that allows for direct observation of sickled blood flow in a physiologic relevant system. Materials and Methods Whole blood was drawn from 6 patients with sickle cell disease (HbSS or HbSC) as a part of routine blood work under an IRB approved protocol. The cohort included both pediatric and adult patients both on and off hydroxyurea. A stock solution of voxelotor in DMSO (dimethylsulfoxide) was mixed and stored in -20C until use. Red blood cells (RBCs) were isolated using centrifugation and fixed to 25% hematocrit with saline. Voxelotor was added to the blood samples for a final concentration of 500 uM. Voxelotor treated samples were then incubated at 37C for one hour. An untreated, non-incubated aliquot from each patient sample was also obtained to serve a control. From two patient samples, a DMSO vehicle control was also incubated at 37C for one hour to serve as an additional control. Using an electronic pressure regulator, blood from each treatment was then driven through a microfluidic device at a constant pressure and was exposed to hypoxic conditions while RBC velocity data was collected. The microfluidic device design and fabrication in this experiment is described in previously published studies(Wood et al, 2012; Valdez et al, 2019). Briefly, a 3-layer microfluidic device constructed of polydimethylsiloxane (PDMS) consists of a blood, hydration, and gas layer. Saline is perfused through the hydration layer to prevent blood evaporation throughout the experiment. Oxygen gas is pushed through the gas layer, exposing flowing blood to a specific oxygen tension achieved using a mixing setup supplied by air and nitrogen tanks. A fiber optic sensor records oxygen tension within the gas layer throughout the experiment. Deoxygenation-oxygenation cycles were conducted using oxygen saturations from 0 to 21% (0 to 160mmHg pO2). With each deoxygenation cycle after 0%, oxygen saturations were up titrated in a stepwise fashion until oxygen-independent flow was observed. RBC velocity was evaluated by tracking cell movement in the microchannel using high frame-rate imaging and computation video processing. Results and Conclusion A reduction in velocity occurs when sickle RBCs are exposed to deoxygenated conditions as seen in one sample example tracing in figure 1. However, the addition of voxelotor at 500 uM improved the blood flow response to deoxygenation, as RBCs treated with voxelotor had a reduction in velocity change compared to vehicle control and untreated samples when exposed to hypoxic conditions as low as 0 mmgHg oxygen (figure 2). Additionally, voxelotor treated samples began to experience oxygen-independent velocity at lower oxygen tensions compared to the controls. By inhibiting polymerization, voxelotor improves sensitivity of sickle RBC blood flow response in hypoxic conditions. While polymerization is one aspect of sickle cell disease, we would like to explore further effects of voxelotor on other aspects of the understood pathophysiology of the disease such as effects on adhesion in future experiments. Disclosures No relevant conflicts of interest to declare.

Aspartate Aminotransferase as a Predictor of Intense Exercise Influence Red Blood Cell

2014 ◽  
Vol 46 ◽  
pp. 846-847
Author(s):  
Mu-Tsung Chen ◽  
Li-Chen Lee ◽  
Shih-Pei Chang ◽  
Chien-Wen Hou
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Aspartate Aminotransferase ◽  
Intense Exercise
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