Materials Biotechnology and Blood Substitutes

MRS Bulletin ◽  
1991 ◽  
Vol 16 (9) ◽  
pp. 78-81 ◽  
Author(s):  
Nir Kossovsky ◽  
David Millett
Keyword(s):  
Synergistic Effects ◽  
Immune Surveillance ◽  
Oxygen Affinity ◽  
Blood Substitutes ◽  
Oxygen Binding ◽  
Low Oxygen ◽  
Cooperative Effects ◽  
Sigmoidal Curve ◽  
Hemoglobin Molecule ◽  
High Oxygen Affinity

Blood is a dispersion of formed elements in an aqueous colloid. The combined mass of the formed elements of blood measure on average 30 ml per kg body weight, or about the same weight as the liver. The colloidal phase of blood contains numerous organic factors that play important primary and supporting roles in homeostasis, including immune surveillance, coagulation, and nutrient transport.Erythrocytes (red blood cells) are the principle formed elements and provide the life-sustaining function, in conjunction with the heart, lungs, blood vessels and kidneys, of transporting and protecting the oxygen-carrying pigment, hemoglobin, to the tissues. The oxygen-binding properties of hemoglobin are sensitive to factors such as the cooperative effects of O2 binding, pH and CO2 levels, and the presence of other metabolic intermediates such as 2,3-diphosphoglycerate. The synergistic effects of these factors produce a well-known sigmoidal curve plot of the relationship between oxygen affinity and the partial pressure of oxygen (pO2): there is high oxygen affinity in the lung where the pO2 is high, and a low oxygen affinity in the tissues, where the pO2 is low. Uptake and delivery of oxygen by hemoglobin is associated with considerable spatial rearrangement of the hemoglobin molecule.Blood is a non-Newtonian suspension. Its viscosity is a function of both the vascular diameter and the concentration of erythrocytes. At a normal hematocrit of 40%, the viscosity of blood ranges between 2 and 4 Pa s as measured in tubes ranging 10–1,500 μm diameter. The osmolality of blood serum is 275–295 mOsm/1.

scholarly journals Salvage of focal cerebral ischemic damage by transfusion of high O2-affinity recombinant hemoglobin polymers in mouse

2006 ◽  
Vol 100 (5) ◽  
pp. 1688-1691 ◽  
Author(s):  
Masaaki Nemoto ◽  
Toshiaki Mito ◽  
William S Brinigar ◽  
Clara Fronticelli ◽  
Raymond C. Koehler
Keyword(s):  
Infarct Volume ◽  
Expression System ◽  
Oxygen Affinity ◽  
Blood Substitutes ◽  
High Oxygen ◽  
Α Subunit ◽  
Hemoglobin Molecule ◽  
High Oxygen Affinity ◽  
Escherichia Coli Expression ◽  
Cerebral Ischemic

Cell-free hemoglobin solutions with high oxygen affinity might be beneficial for selectively delivering oxygen to ischemic tissue. A recombinant hybrid hemoglobin molecule was designed using the human α-subunit and the bovine β-subunit, with placement of surface cysteines to permit disulfide bond polymerization of the tetramers. The resulting protein generated from an Escherichia coli expression system had a molecular mass >1 MDa, a P50 of ∼3 Torr, and a cooperativity of n = 1.0. Anesthetized mice were transfused during 2-h occlusion of the middle cerebral artery. Compared with transfusion with 5% albumin, cerebral infarct volume was reduced by 41% with transfusion of a 3% solution of the high oxygen-affinity hemoglobin polymer and by 50% with transfusion of a 6% solution of the polymer. Transfusion of a 6% solution of a 500-kDa polymer possessing a P50 of 17 Torr and a cooperativity of n = 2.0 resulted in a 66% reduction of infarct volume. These results indicate that cell-free Hb polymers with P50 values much lower than that of red blood cell hemoglobin are highly capable of salvaging ischemic brain. The assumption that the P50 of blood substitutes should be similar to that of blood might not be warranted when used during ischemic conditions.

scholarly journals Haemoglobin polymorphisms affect the oxygen-binding properties in Atlantic cod populations

2008 ◽  
Vol 276 (1658) ◽  
pp. 833-841 ◽  
Author(s):  
Øivind Andersen ◽  
Ola Frang Wetten ◽  
Maria Cristina De Rosa ◽  
Carl Andre ◽  
Cristiana Carelli Alinovi ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Quaternary Structure ◽  
Atlantic Cod ◽  
Three Dimensional ◽  
Oxygen Affinity ◽  
Oxygen Binding ◽  
Low Oxygen ◽  
Binding Properties ◽  
Important Species ◽  
The North

A major challenge in evolutionary biology is to identify the genes underlying adaptation. The oxygen-transporting haemoglobins directly link external conditions with metabolic needs and therefore represent a unique system for studying environmental effects on molecular evolution. We have discovered two haemoglobin polymorphisms in Atlantic cod populations inhabiting varying temperature and oxygen regimes in the North Atlantic. Three-dimensional modelling of the tetrameric haemoglobin structure demonstrated that the two amino acid replacements Met55β 1 Val and Lys62β 1 Ala are located at crucial positions of the α 1 β 1 subunit interface and haem pocket, respectively. The replacements are proposed to affect the oxygen-binding properties by modifying the haemoglobin quaternary structure and electrostatic feature. Intriguingly, the same molecular mechanism for facilitating oxygen binding is found in avian species adapted to high altitudes, illustrating convergent evolution in water- and air-breathing vertebrates to reduction in environmental oxygen availability. Cod populations inhabiting the cold Arctic waters and the low-oxygen Baltic Sea seem well adapted to these conditions by possessing the high oxygen affinity Val55–Ala62 haplotype, while the temperature-insensitive Met55–Lys62 haplotype predominates in the southern populations. The distinct distributions of the functionally different haemoglobin variants indicate that the present biogeography of this ecologically and economically important species might be seriously affected by global warming.

Influence of carbon monoxide on hemoglobin-oxygen binding

1976 ◽  
Vol 41 (6) ◽  
pp. 893-899 ◽  
Author(s):  
M. P. Hlastala ◽  
H. P. McKenna ◽  
R. L. Franada ◽  
J. C. Detter
Keyword(s):  
Carbon Monoxide ◽  
Oxygen Affinity ◽  
Co2 Concentration ◽  
Bohr Effect ◽  
Oxygen Binding ◽  
Dissociation Curve ◽  
Low Oxygen ◽  
Oxygen Dissociation ◽  
Initial Binding ◽  
Fixed Acid

The oxygen dissociation curve and Bohr effect were measured in normal whole blood as a function of carboxyhemoglobin concentration [HbCO]. pH was changed by varying CO2 concentration (CO2 Bohr effect) or by addition of isotonic NaOH or HCl at constant PCO2 (fixed acid Bohr effect). As [HbCO] varied through the range of 2, 25, 50, and 75%, P50 was 26.3, 18.0, 11.6, and 6.5 mmHg, respectively. CO2 Bohr effect was highest at low oxygen saturations. This effect did not change as [HbCO] was increased. However, as [HbCO] was increased from 2 to 75%, the fixed acid Bohr factor increased in magnitude from -0.20 to -0.80 at very low oxygen saturations. The effect of molecular CO2 binding (carbamino) on oxygen affinity was eliminated at high [HbCO]. These results are consistent with the initial binding of O2 or CO to thealpha-chain of hemoglobin. The results also suggest that heme-heme interaction is different for oxygen than for carbon monoxide.

scholarly journals Hemoglobin Great Lakes (beta 68 [E12] leucine replaced by histidine): a new high-affinity hemoglobin

Blood ◽  
1981 ◽  
Vol 58 (4) ◽  
pp. 813-817 ◽  
Author(s):  
S Rahbar ◽  
K Winkler ◽  
J Louis ◽  
C Rea ◽  
K Blume ◽  
...  
Keyword(s):  
Great Lakes ◽  
Electrophoretic Mobility ◽  
Tertiary Structure ◽  
Oxygen Affinity ◽  
Heme Binding ◽  
Hemoglobin Variant ◽  
Heme Pocket ◽  
Hemoglobin Molecule ◽  
Normal Stability ◽  
High Oxygen Affinity

Abstract Hemoglobin Great Lakes, beta 68 (E12) Leu replaced by His is a new high oxygen affinity hemoglobin variant discovered in a 29-yr-old female having numerous hospitalizations for thrombophlebitis associated with mild erythrocytosis. The mutant hemoglobin has normal stability and normal electrophoretic mobility, but increased oxygen affinity (P-50 16.1 mm Hg at 37 degrees C, pH 7.4) and reduced cooperativity. The abnormal beta-chain could be separated on globin chain chromatography on carboxymethyl/cellulose in spite of the normal electrophoretic mobility of the intact hemoglobin. The leucyl residue at beta 68th position (E12) is in the middle of E-helix, which is part of the heme pocket and next to the valine (E11), which is the heme binding site. The substitution of proline for leucine in hemoglobin Mizuho resulted in the distortion of tertiary structure of the beta-chains and lead to a serious instability of hemoglobin molecule. However, the substitution of this residue by histidine in hemoglobin Great Lakes is not associated with hemoglobin instability.

Acellular haemoglobin attenuates hypoxia-inducible factor-1α (HIF-1α) and its target genes in haemodiluted rats

2008 ◽  
Vol 414 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Dominador J. Manalo ◽  
Paul W. Buehler ◽  
Jin Hyen Baek ◽  
Omer Butt ◽  
Felice D'agnillo ◽  
...  
Keyword(s):  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Oxygen Affinity ◽  
Blood Substitutes ◽  
Oxygen Deficit ◽  
Adaptation To Hypoxia ◽  
Low Oxygen ◽  
Hypoxia Inducible Factor 1Α ◽  
Haem Oxygenase ◽  
Oxide Synthase

Hb (haemoglobin)-based blood substitutes represent a class of therapeutics designed to correct oxygen deficit under conditions of anaemia and traumatic blood loss. The influences of these agents on HIF-1α (hypoxia-inducible factor-1α) target genes involved in adaptation to hypoxia have so far not been studied. In the study presented here, rats underwent 80% ET (exchange transfusion) with either HS (hetastarch) or a polymerized Hb OG (Oxyglobin®). HS induced dramatic EPO (erythropoietin) gene transcription, reaching a maximum at 4 h post-ET. In contrast, OG suppressed EPO transcription until approx. 24 h post-ET. Large plasma EPO levels that were observed post-ET with HS were significantly blunted in animals transfused with OG. OG, unlike HS, induced a sharp increase in HO-1 (haem oxygenase-1) transcription at 4 h, which declined rapidly within 24 h, whereas modest increases in iNOS [inducible (nitric oxide synthase)] and constitutive NOS [eNOS (endothelial NOS)] were detected over the control. Our results demonstrate for the first time that severe haemodilution-induced erythropoietic responses in kidneys were attenuated by a low-oxygen-affinity cell-free Hb and suggest that tissue-specific oxygen-sensing pathways can be influenced by allosterically modified Hbs.

scholarly journals Shifts in microbial transcription patterns prior to onset of Necrotizing enterocolitis may indicate low oxygen levels in the gut

2018 ◽  
Author(s):  
Yonatan Sher ◽  
Matthew R. Olm ◽  
Tali Raveh-Sadka ◽  
Christopher Brown ◽  
Ruth Sher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Oxygen Affinity ◽  
High Oxygen ◽  
Host Cells ◽  
Multiple Time ◽  
List Type ◽  
Low Oxygen ◽  
High Oxygen Affinity

SummaryPremature infants are at risk for developing necrotizing enterocolitis (NEC), an inflammatory disease that can progress to necrosis of gut tissue. Previous attempts have failed to identify any consistent predictor of NEC. We hypothesized that prior to the appearance of NEC symptoms, the gut microbiome shifts in its transcriptional profile. To test this hypothesis we integrated genome-resolved metagenomic and metatranscriptomic data from multiple time-points in the first month of life of four preterm infants, two of whom later developed NEC. Gut microbiomes of NEC infants showed increased transcription of high oxygen affinity cytochrome oxidases and lower transcription of genes to detoxify nitric oxide, an antimicrobial compound released by host cells. These results, and high transcription of H2 production genes, suggest low O2 conditions prior to NEC onset, and are consistent with hypoxic conditions in diseased gut tissue. The findings motivate further testing of transcript data as a predictor of NEC.HighlightsTranscription of high oxygen affinity microbial cytochrome oxidase may predict necrotizing enterocolitis (NEC) development.Lower transcription of microbial genes to detoxify nitric oxide (NO) may also predict NEC development.Higher transcription of H2 production genes by Escherichia sp. was found in the gut of premature infants that develop NEC.

scholarly journals Antarctic Fish Blood: Respiratory Properties and the Effects Of Thermal Acclimation

1984 ◽  
Vol 109 (1) ◽  
pp. 265-279
Author(s):  
VILHELM TETENS ◽  
RUFUS M. G. WELLS ◽  
ARTHUR L. DEVRIES
Keyword(s):  
Oxygen Affinity ◽  
Antarctic Fish ◽  
Thermal Acclimation ◽  
Temperate Species ◽  
Molar Ratio ◽  
Oxygen Binding ◽  
Blood Oxygen ◽  
Low Oxygen ◽  
Blood Oxygen Affinity

1. The effects of thermal acclimation on whole blood oxygen affinity were examined in the antarctic fish Pagothenia borchgrevinki. 2. 4.5°C-acclimated fish had a P50 value of 26.7 mmHg at pH 8.1, compared to 20.7 mmHg for −1.5°C-acclimated fish. The apparent heat of oxygenation, ΔH = −26.7 kJ mol−1, is comparable to values for temperate species. 3. Warm-acclimation was followed by an increased ATP: Hb4 molar ratio, resulting in an augmentation of the thermal effect on oxy-haemoglobin affinity. This may be considered adaptive in a constantly well oxygenated environment, where oxygen loading at the gills is secured. Unloading to the tissues is thereby enhanced, supporting an elevated rate of aerobic metabolism at higher temperatures. 4. In vivo blood pH was high, between 8.10 and 8.25 at −1.5°C. Astrup titration revealed arterial CO2 tensions of less than 0.8 mmHg, indicating relative hyperventilation and low oxygen extraction efficiency in antarctic fish. 5. Blood oxygen affinities of four antarctic nototheniid species were low (P50 between 11.9 and 20.7 mmHg at pH 8.1 and --1.5°C) in comparison with the temperate species Notothenia angustata (P50 = 10.8 mmHg). The zoarcid Rhigophila dearborni had a high blood oxygen affinity (P50 = 4.3 mmHg). Blood oxygen-binding properties are discussed in relation to the polar environment, mode of life, and the concept of cold adaptation.

Regulation of Blood Oxygen Affinity in the Australian Blackfish Gadopsis Marmoratus: I. Correlations between Oxygen-binding Properties, Habitat and Swimming Behaviour

1982 ◽  
Vol 99 (1) ◽  
pp. 223-243
Author(s):  
G. P. DOBSON ◽  
J. BALDWIN
Keyword(s):  
Whole Blood ◽  
Oxygen Affinity ◽  
Swimming Behaviour ◽  
Oxygen Binding ◽  
Blood Oxygen ◽  
Low Oxygen ◽  
Binding Properties ◽  
Molar Ratios ◽  
Blood Oxygen Affinity ◽  
Low Oxygen Affinity

1. The regulation of whole blood oxygen affinity in the freshwater blackfish Gadopsis marmoratus Richardson has been examined, and correlations made between oxygen-binding properties and the habitat and swimming behaviour of the fish. 2. Blackfish whole blood has a low oxygen affinity relative to other fish bloods reported in the literature. This is not due to a low oxygen affinity of the stripped haemoglobins, but arises from interactions between haemoglobin and intraerythrocytic modulators. 3. The presence of high concentrations of ATP, and to a lesser extent GTP, in the erythrocyte, together with the effect of these nucleoside triphosphates on the oxygen affinity of haemoglobin solutions at physiological NTP: Hb4 molar ratios, demonstrates that this class of compounds is a major regulator of oxygen affinity in blackfish blood. 4. The oxygen affinities of whole blood and haemoglobin solutions are sensitive to pH, with haemoglobin solutions displaying a relatively large alkaline Bohr coefficient of - 1.05 over the physiologically relevant pH range of 6.5–7.0. 5. Although increasing Pco2, lowers the oxygen affinity of whole blood, it does so only through the effect on pH, as pH-buffered haemoglobin solutions show no oxygen-linked CO2 binding. This lack of oxygen-linked CO2 binding has not been reported for any other naturally occurring vertebrate haemoglobins. 6. Muscle morphology and biochemistry, and behavioural observations, indicate that the blackfish uses anaerobic energy metabolism during rapid swimming and in recovery. 7. It is concluded that the oxygen-binding properties of blackfish blood reflect adaptations for maintaining adequate tissue oxygenation for animals at rest and during slow sustained swimming in waters of high oxygen tensions.

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