Oxidized Mono-, Di-, Tri-, and Polysaccharides as Potential Hemoglobin Cross-Linking Reagents for the Synthesis of High Oxygen Affinity Artificial Blood Substitutes

2004 ◽  
Vol 20 (3) ◽  
pp. 953-962 ◽  
Author(s):  
J.H. Eike ◽  
A.F. Palmer
Keyword(s):  
Oxygen Affinity ◽  
Blood Substitutes ◽  
High Oxygen ◽  
Cross Linking ◽  
Artificial Blood ◽  
High Oxygen Affinity

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.

Investigation of the Molecular Basis of High Oxygen Affinity Hemoglobin Brigham (α2Aβ2100 Pro→Leu) In a Subject with Familial Erythrocytosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4806-4806
Author(s):  
Bindu Abraham ◽  
Yiping Jia ◽  
Francine Wood ◽  
Chad Reiter ◽  
Jay Nelson Lozier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Whole Blood ◽  
Conflicts Of Interest ◽  
Ph Dependence ◽  
Oxygen Affinity ◽  
Blood Substitutes ◽  
High Oxygen ◽  
Hill Coefficient ◽  
Oxygen Dissociation ◽  
High Oxygen Affinity

Abstract Abstract 4806 A 40 year old female was seen at the NIH Clinical Center for polycythemia (Hb 16.3 g/dL) and recurrent pulmonary embolism. It was determined that she was a member of the original kindred with familial erythrocytosis due to the high oxygen affinity Hb Brigham first reported by Lokich et al (JCI, 1973;52:2060-7) where leucine replaces proline at amino acid 100 in the Hb beta globin chain. We sought to isolate and characterize the abnormal Hb in order to elucidate the mechanism by which the amino acid substitution causes a high affinity for oxygen. Fresh RBCs exhibited high oxygen affinity (P50 = 23.6 mmHg; a Hill coefficient of n=2.02) compared to that of fresh normal RBCs (P50 = 31.1 mmHg; n=2.1) in Hemox buffer, pH 7.4 at 37°C using the TCS automated Hemox analyzer. After 2, 3-diphosphoglycerate (DPG) depletion (24 hours incubation of RBCs at room temp) the RBCs exhibited a higher oxygen affinity, that decreased when inositol hexaphosphate (a 2, 3-DPG analogue) was electroporated into erythrocytes, indicating a normal allosteric response at the 2,3-DPG binding site. The Bohr effect (pH dependence of oxygen affinity) of stripped Hb Brigham was reduced by approximately 30% when compared to that of HbA0. Hb Brigham was separated from Hb A in this subject using strong cationic HPLC and the molecular composition of each protein was verified by tryptic peptide mapping and mass spectrometry of purified peptides. The purified fractions; F1 (HbA0) and FII (Hb Brigham) which represent approximately 60% and 40% of total Hb, respectively, were characterized using rapid mixing stopped-flow kinetics and compared to RBCs Brigham. The time course of the oxygen dissociation reaction from both (oxy) fractions in the presence of sodium dithionite were monophasic with apparent rate constants derived for FI (koff = 38 s-1) which is comparable to that of whole blood (koff = 37.9 s-1) and that of normal control HbAo (koff = 39.6 s-1). However, the rate constant for oxygen dissociation from FII was slightly reduced (koff = 33.9 s-1). To further characterize oxygen dissociation kinetics, carbon monoxide (CO) combination kinetics with the (deoxy) forms of each hemoglobin were also carried out. The kinetics of CO binding to deoxyHb were comparable between both purified fractions and whole blood (kon =0.22-0.23 mM-1 s-1). Unlike FI or control Hb A0, FII showed no change in its CO binding kinetics in the presence of increasing concentrations of IHP. We propose that the IHP-dependent difference in CO binding resulted from destabilization of the deoxy (tense) structure due to the β2 100 Pro→Leu substitution. Analysis of purified Hb Brigham, which was not previously possible, provides valuable insights into the contribution of this mutant to the overall oxygen affinity in this patient and may be useful in the design and evaluation of hemoglobin-based blood substitutes. Disclosures: No relevant conflicts of interest to declare.

Hemoglobin fort gordon or α2β2145 Tyr → Asp, a new high-oxygen-affinity hemoglobin variant

1975 ◽  
Vol 400 (2) ◽  
pp. 343-347 ◽  
Author(s):  
H.B. Kleckner ◽  
J.B. Wilson ◽  
J.G. Lindeman ◽  
P.D. Stevens ◽  
G. Niazi ◽  
...  
Keyword(s):  
Oxygen Affinity ◽  
High Oxygen ◽  
Hemoglobin Variant ◽  
High Oxygen Affinity

Germline mosaicism for an alanine to valine substitution at residue ? 140 in hemoglobin Puttelange, a new variant with high oxygen affinity

1995 ◽  
Vol 96 (6) ◽  
pp. 711-716 ◽  
Author(s):  
H. Wajcman ◽  
E. Girodon ◽  
D. Prom� ◽  
M.L. North ◽  
F. Plassa ◽  
...  
Keyword(s):  
Oxygen Affinity ◽  
High Oxygen ◽  
Germline Mosaicism ◽  
New Variant ◽  
High Oxygen Affinity

Unusual finding of high oxygen affinity haemoglobinopathy treated with phlebotomy: a rare but predictable union

2021 ◽  
pp. 103290
Author(s):  
Epifania Rita Testa ◽  
Adriana Masotti ◽  
Patrizia Valeri ◽  
Luciana Geremia ◽  
Valeria Brunetta ◽  
...  
Keyword(s):  
Oxygen Affinity ◽  
High Oxygen ◽  
High Oxygen Affinity ◽  
Unusual Finding

scholarly journals Haemoglobin Olympia {β Codon 20 (B2) G→A, Val→Met}: A Silent Haemoglobin Variant

2021 ◽  
Author(s):  
Abhay A Bhave ◽  
Lakshmi Iyer ◽  
Nawal Kazi ◽  
Manju Gorivale ◽  
Anita Nadkarni
Keyword(s):  
High Performance ◽  
Extended Family ◽  
Globin Gene ◽  
Oxygen Affinity ◽  
High Oxygen ◽  
Cerebral Vessel ◽  
Haemoglobin Variant ◽  
First Case ◽  
History Of ◽  
High Oxygen Affinity

High oxygen affinity haemoglobin variants are rare and often underdiagnosed in persistent erythrocytosis with no apparent aetiology. Here the author present a 29-year-old Indian male patient with a long-standing history of erythrocytosis which was incidentally detected. The proband had a prothrombotic family history of cerebral vessel stroke in his paternal grandfather at a young age and unexplained erythrocytosis in his father and brother. A review of his haemograms showed persistent high haemoglobin values. Routine tests did not reveal any specific aetiology and haemoglobin electrophoresis by High-Performance Liquid Chromatography (HPLC) showed absence of any abnormal peak or unstable haemoglobin. DNA sequencing of the β globin gene revealed heterozygosity for codon 20 {GTG→ATG, Valine (Val)→ Methionine (Met)} mutation confirming the presence of an electrophoretically silent Hb variant - Haemoglobin Olympia in him and his extended family members. This case study emphasises importance of this rare entity of high oxygen affinity haemoglobin variant as a differential diagnosis while screening for erythrocytosis. This is the first case report of Haemoglobin Olympia from India reported in the literature.

scholarly journals A Newly Characterized Hemoglobin Variant with a High Oxygen Affinity, Hb Fuchu-II, Presenting with Acute Myocardial Infarction

2016 ◽  
Vol 55 (3) ◽  
pp. 285-287
Author(s):  
Raku Son ◽  
Takakazu Higuchi ◽  
Atsushi Mizuno ◽  
Ryosuke Koyamada ◽  
Sadamu Okada ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Oxygen Affinity ◽  
High Oxygen ◽  
Hemoglobin Variant ◽  
High Oxygen Affinity

Novel High Oxygen Affinity Hemoglobin Variant in a Patient with Polycythemia: Hb Kennisis [β85(F1)Phe→Leu (TTT>TTG); HBB: c.258T>G]

Hemoglobin ◽  
2020 ◽  
Vol 44 (1) ◽  
pp. 10-12
Author(s):  
Ibrahim Al Nabhani ◽  
John C. Aneke ◽  
Madeleine Verhovsek ◽  
Barry Eng ◽  
Kevin H.M. Kuo ◽  
...  
Keyword(s):  
Oxygen Affinity ◽  
High Oxygen ◽  
Hemoglobin Variant ◽  
High Oxygen Affinity
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