Red Blood Cell Oxygen Affinity Research Articles

Modulation of red blood cell oxygen affinity with a novel allosteric modifier of hemoglobin is additive to the Bohr effect

PurposeThe Bohr effect describes hemoglobin's affinity for oxygen dependent on solution pH. Within pH range 6.0–8.5, hemoglobin's oxygen affinity decreases with decreasing pH. This results in increased oxygen delivery to metabolically active, acidic tissues and improved oxygen uptake in basic regions including lung tissue. Myo-Inositol tripyrophosphate (ITPP) translocates the erythrocyte membrane and allosterically modifies hemoglobin (Hb). We tested the hypothesis that ITPP does not abrogate the Bohr effect. MethodsExperiments were conducted to determine the effect of increasing concentrations of ITPP on P50 with varying pH. We incubated 10 mL red blood cells at 37 °C for 1 h with ITPP concentrations from 0 to 240 mM. The Clark oxygen electrode (Hemox-Analyzer; TCS Scientific, New Hope, PA) determined oxygen affinity of each sample, in triplicate, using buffers pH 6.8, 7.4, and 7.6. A mixed linear regression model with fixed effects for ITPP concentration and pH was used. ResultsIncreasing ITPP concentration and decreasing pH increased P50 (p < 0.0001 for ITPP concentration, p < 0.0001 for pH). ITPP modulated increased P50 in normal pH (7.4) and acidic condition pH (6.8); with no effect at alkaline pH (7.6). ConclusionThe Bohr effect is conserved, with ITPP augmenting the decreased oxygen affinity seen with tissue acidosis, while not affecting oxygen affinity in conditions similar to a pulmonary microenvironment.

Single-cell measurement of red blood cell oxygen affinity

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

Modulation of Perfusion and Oxygenation by Red Blood Cell Oxygen Affinity during Acute Anemia

Responses to exchange transfusion using red blood cells (RBCs) with modified hemoglobin (Hb) oxygen (O(2)) affinity were studied in the hamster window chamber model during acute anemia to determine its role on microvascular perfusion and tissue oxygenation. Allosteric effectors were introduced in the RBCs by electroporation. Inositol hexaphosphate (IHP) and 5-hydroxymethyl-2-furfural (5HMF) were used to decrease and increase Hb-O(2) affinity. In vitro P50s (partial pressure of O(2) at 50% Hb saturation) were modified to 10, 25, 45, and 50 mm Hg (normal P50 is 32 mm Hg). Allosteric effectors also decreased the Hill coefficient. Anemic condition was induced by isovolemic hemodilution exchanges using 6% dextran 70 kD to 18% hematocrit (Hct). Modified RBCs (at 18% Hct in 5% albumin solution) were infused by exchange transfusion of 35% of blood volume. Systemic parameters, microvascular perfusion, capillary perfusion (functional capillary density, FCD), and microvascular Po(2) levels were measured. RBcs with P50 of 45 mm Hg increased tissue Po(2) and decreased O(2) delivery (Do(2)) and extraction (Vo(2)) and RBCs with P50 of 60 mmHg reduced FCD, microvascular flow, tissue Po(2), Do(2) and Vo(2). Erythrocytes with increased Hb-O(2) affinity maintained hemodynamic conditions, Do(2) and decreased tissue Po(2). This study shows that in an anemic condition, maximal tissue Po(2) does not correspond to maximal Do(2) and Vo(2).

Rapid method for determining effect of agents on oxyhemoglobin dissociation curves.

ARTICLESRapid method for determining effect of agents on oxyhemoglobin dissociation curvesI. S. Longmuir, and J. ChowI. S. Longmuir, and J. ChowPublished Online:01 Mar 1970https://doi.org/10.1152/jappl.1970.28.3.343MoreSectionsPDF (598 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByAdaptation of Polarographic Oxygen Sensors for Biochemical Assays31 October 2006Blood Oxygen Transport Properties during Migration to Higher Altitude of Wild Quail, Coturnix coturnix coturnixPhysiological Zoology, Vol. 69, No. 4Changes in haemoglobin oxygen affinity and erythrocytic 2,3-BPG in ethanol-treated ratsGeneral Pharmacology: The Vascular System, Vol. 21, No. 3Blood respiratory properties of the mudsucker fish Labeo capensis (Smith)Comparative Biochemistry and Physiology Part A: Physiology, Vol. 83, No. 2Oxygen affinity of blood of adult domestic chicken and red jungle fowlRespiration Physiology, Vol. 52, No. 1Depression of intramyocardial oxyhemoglobin dissociation by angiographic contrast mediaAmerican Heart Journal, Vol. 99, No. 2A comparative study of the respiratory properties of bird bloodRespiration Physiology, Vol. 31, No. 3Oxygen affinity of avian bloodRespiration Physiology, Vol. 31, No. 1The oxygen affinity of chicken haemoglobin in whole blood and erythrocyte suspensionsRespiration Physiology, Vol. 27, No. 1Some studies on blood of the Florida manatee, Trichechus manatus latirostrisComparative Biochemistry and Physiology Part A: Physiology, Vol. 55, No. 4Studies on avian erythrocyte metabolism—iv. Relationship between the major phosphorylated metabolic intermediates and oxygen affinity of whole blood in adults and embryos in several galliformesComparative Biochemistry and Physiology Part A: Physiology, Vol. 55, No. 1Oxygen and carbon dioxide dissociation of duck bloodRespiration Physiology, Vol. 24, No. 1Metabolic changes in avian blood and their effects on determination of blood gases and pHRespiration Physiology, Vol. 23, No. 3Studies on the red blood cell oxygen affinity and 2,3-diphosphoglyceric acid in the hibernating woodchuck (Marmota monax)Comparative Biochemistry and Physiology Part A: Physiology, Vol. 48, No. 3Oxygen affinity of bird bloodRespiration Physiology, Vol. 20, No. 3The effects of pacing on oxygen hemoglobin dissociation and oxygen carrying capacity in patients suspected of coronary artery diseaseAmerican Heart Journal, Vol. 85, No. 5Dissociation curve of bird blood and effect of red cell oxygen consumptionRespiration Physiology, Vol. 17, No. 3 More from this issue > Volume 28Issue 3March 1970Pages 343-345 Copyright & PermissionsCopyright © 1970 the American Physiological Societyhttps://doi.org/10.1152/jappl.1970.28.3.343PubMed5414767History Published online 1 March 1970 Published in print 1 March 1970 Metrics

Oxygen carrying capacity of the blood of dormant ground squirrels.

ArticleOxygen Carrying Capacity of the Blood of Dormant Ground SquirrelsArthur Svihla, and Howard C. BowmanArthur SvihlaFrom the University of Washington, Seattle, Washington, and Howard C. BowmanFrom the University of Washington, Seattle, WashingtonPublished Online:31 Oct 1952https://doi.org/10.1152/ajplegacy.1952.171.2.479MoreSectionsPDF (391 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySquirrels24 January 2020Hibernation and Gas Exchange1 January 2011Quantitative and functional analysis of peripheral blood mononuclear cells in European brown bear (Ursus arctos arctos)Comparative Biochemistry and Physiology Part A: Physiology, Vol. 112, No. 3-4Seasonal patterns in the physiology of the European brown bear (Ursus arctos arctos) in FinlandComparative Biochemistry and Physiology Part A: Physiology, Vol. 109, No. 3Respiration and Acid-Base State in HibernationCirculatory responses of Rana catesbeiana to temperature, season and previous thermal historyComparative Biochemistry and Physiology Part A: Physiology, Vol. 51, No. 1Studies on the red blood cell oxygen affinity and 2,3-diphosphoglyceric acid in the hibernating woodchuck (Marmota monax)Comparative Biochemistry and Physiology Part A: Physiology, Vol. 48, No. 3Several blood and circulatory changes in the hibernation of the 13-lined ground squirrel, Citellus tridecemlineatusComparative Biochemistry and Physiology Part A: Physiology, Vol. 44, No. 2Effects of simulated high altitude on hibernating and non-hibernating rodentsComparative Biochemistry and Physiology, Vol. 34, No. 4Environmental temperature and the body fluid system of the fresh-water teleost—III. Hematology and blood volume of thermally acclimated brook trout, Salvelinus fontinalisComparative Biochemistry and Physiology, Vol. 28, No. 2Oxygen and carbon dioxide content of blood in toad (bufo melanostictus) during hibernation and non-hibernationComparative Biochemistry and Physiology, Vol. 18, No. 3HibernationThe Care and Use of Hibernating MammalsHistochemical localization of some enzymes in the kidney of a hibernatorJournal of Cellular and Comparative Physiology, Vol. 56, No. 2The effect of hibernation on the replacement of blood in the golden hamsterJournal of Experimental Zoology, Vol. 136, No. 3Blood Hepari Level and the Status of Blood Coagulation in Cats During Hypothermia26 September 2008 | Archives Internationales de Physiologie et de Biochimie, Vol. 64, No. 1 More from this issue > Volume 171Issue 2October 1952Pages 479-481 Copyright & PermissionsCopyright © 1952 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1952.171.2.479PubMed13007819History Received 28 May 1952 Published online 31 October 1952 Published in print 31 October 1952 Metrics