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Hemoglobin-based Blood Substitutes: Oxygen Carriers, Pressor Agents, Or Oxidants?

A. Alayash
Published 1999 · Chemistry, Medicine

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Hemoglobin-based blood substitutes are being developed as oxygen-carrying agents for the prevention of ischemic tissue damage and hypovolemic (low blood volume) shock. The ability of cell-free hemoglobin blood substitutes to affect vascular tone through the removal of nitric oxide has also prompted an evaluation of their usefulness for maintaining blood pressure in critically ill patients. Before the clinical potential of these substitutes can be fully realized, however, concerns remain as to the intrinsic toxicity of the hemoglobin molecule, particularly the interference of the heme prosthetic group with the tissue oxidant/antioxidant balance. This review provides some insights into the complex redox chemistry of hemoglobin and places an emphasis on how current knowledge may be exploited both to selectively enhance/suppress specific chemical reaction pathway(s) and to ultimately design safer hemoglobin-based therapeutics.
This paper references
10.1021/BC960069P
Surface modification of hemoglobin vesicles with poly(ethylene glycol) and effects on aggregation, viscosity, and blood flow during 90% exchange transfusion in anesthetized rats.
H. Sakai (1997)
Baxter formally pulls plug on HemAssist blood substitute , takes charges
E. CashonR. (1998)
10.1038/NBT0798-672
Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin
D. Doherty (1998)
10.1016/S0167-7799(98)01242-6
Future prospects for artificial blood.
T. Chang (1999)
10.1007/978-1-4612-4114-0_10
Carbon Dioxide Transport by Hemoglobin-Based Blood Substitutes
R. Winslow (1996)
principles, methods, products and clinical trials Vol
Nelson (1998)
effects of distal pocket mutations on the formation and stability of the ferryl intermediate
A. I. Alayash (1999)
principles, methods, products, and clinical trials
Chang (1998)
Oxidative stress response in vascular endothelial cells exposed to acellular hemoglobin solution
R. Motterlini (1995)
principles, methods, products and clinical trials Vol
J. G. Adamson (1998)
10.1073/PNAS.88.23.10976
In vivo biodistribution of a radiolabeled blood substitute: 99mTc-labeled liposome-encapsulated hemoglobin in an anesthetized rabbit.
A. Rudolph (1991)
10.1016/S0022-2143(99)90003-3
Pharmacology of hemoglobin therapeutics.
A. Gulati (1999)
10.1074/jbc.273.30.18709
Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes*
X. Liu (1998)
Initial evaluation of diasprin cross-linked hemoglobin (DCLHbTM) as a vasopressor in critically ill patients
G. Peah (1997)
10.1152/JAPPL.1998.85.3.993
Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model.
R. Winslow (1998)
10.1016/S1246-7820(05)80074-6
Oxygen delivery and autoxidation of hemoglobin.
M. Marden (1995)
10.1046/j.1537-2995.1995.35795357876.x
Comparison of the efficacy of blood and polyethylene glycol‐hemoglobin in recovery of newborn piglets from hemorrhagic hypotension: effect on blood pressure, cortical oxygen, and extracellular dopamine in the brain
D. Song (1995)
Detection of a ferryl intermediate in an endothelial cell model after hypoxia / reoxygenation
L. McLeod
Peroxidases in chemistry and biology
J. Everse (1990)
10.1074/JBC.274.4.2583
Glutaraldehyde Modification of Recombinant Human Hemoglobin Alters Its Hemodynamic Properties*
M. P. Doyle (1999)
10.1152/JAPPL.1999.86.2.541
Cardiovascular and hemorheological effects of three modified human hemoglobin solutions in hemodiluted rabbits.
A. Caron (1999)
10.1038/NBT0798-667
Polyhemoglobin-superoxide dismutase-catalase as a blood substitute with antioxidant properties
F. D'agnillo (1998)
Cardiovacular and hemorheological effects of dextran-conjugated hemoglobin, (a)-crosslinked hemoglobin, and o-raffinose polymerized hemoglobin in hemodiluted rabbits
A Caron (1999)
10.1016/0022-4804(89)90092-9
Ultrapure, stroma-free, polymerized bovine hemoglobin solution: evaluation of renal toxicity.
R. Lee (1989)
10.1152/JAPPL.1995.79.1.236
Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions.
R. Lee (1995)
10.1038/356258A0
A human recombinant haemoglobin designed for use as a blood substitute
D. Looker (1992)
Comparison of the efficacy of blood and PEG-hemoglobin recovery of newborn piglets from hemorrhagic hypotension
D Song (1995)
10.1074/jbc.273.20.12128
Arterial Blood Pressure Responses to Cell-free Hemoglobin Solutions and the Reaction with Nitric Oxide*
R. Rohlfs (1998)
10.1097/00000542-199301000-00049
Hemoglobin-based Red Cell Substitutes
C. Mackenzie (1993)
a role for ferryl iron
D. W. Goldman (1998)
10.1016/S0022-2143(97)90194-3
Effects of polymerization on the hypertensive action of diaspirin cross-linked hemoglobin in rats.
Z. Abassi (1997)
Blood Substitutes: Principles, Methods, Products, and Clinical Trials
T. Chang (1998)
10.1074/jbc.272.11.7114
The Globin-based Free Radical of Ferryl Hemoglobin Is Detected in Normal Human Blood*
D. Svistunenko (1997)
lipid peroxidation, (-tocopherol, and ascorbate
Buettner (1993)
10.1006/ABBI.1997.0449
Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobins.
A. Alayash (1998)
Free radicals in the vasculature — the good , the bad , and the ugly
V. W. Darley-Usmar (1994)
10.1016/S0022-2143(97)90191-8
Nitric oxide binding and the adverse effects of cell-free hemoglobins: what makes us different from earthworms.
J. Loscalzo (1997)
Nitric oxide: physiology, pathophysiology, and pharmacology.
S. Moncada (1991)
Diffusion-limited reaction of free NO with erythrocytes
X Liu (1998)
10.1161/01.CIR.41.6.989
Experimental and Clinical Studies on Lactate and Pyruvate as Indicators of the Severity of Acute Circulatory Failure (Shock)
M. Weil (1970)
10.1006/ABBI.1995.1061
Reaction of human hemoglobin HbA0 and two cross-linked derivatives with hydrogen peroxide: differential behavior of the ferryl intermediate.
R. Cashon (1995)
10.1016/s0021-9258(17)45394-4
A novel antioxidant role for hemoglobin. The comproportionation of ferrylhemoglobin with oxyhemoglobin.
C. Giulivi (1990)
10.1097/00000658-199004000-00003
The Efficacy of Polymerized Pyridoxylated Hemoglobin Solution as an O2 Carrier
S. Gould (1990)
10.1006/ABBI.1993.1074
The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate.
G. Buettner (1993)
10.7326/0003-4819-105-5-820_2
Hemoglobin: Molecular, Genetic and Clinical Aspects
H. Bunn (1984)
Limitations of the efficacy of hemoglobin oxygen carrying solutions
R. Lee (1995)
10.1016/S0169-409X(99)00050-2
Site-specific modifications and toxicity of blood substitutes. The case of diaspirin cross-linked hemoglobin.
F. D'agnillo (2000)
10.1016/s0021-9258(18)81216-9
The mechanism of metmyoglobin oxidation.
N. K. King (1963)
10.1016/s0021-9258(18)49899-7
Carbon dioxide binding to human hemoglobin cross-linked between the alpha chains.
K. Vandegriff (1991)
10.1016/S0891-5849(98)00092-6
Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide.
D. Wink (1998)
10.3109/10731199809119772
Hemoglobin based oxygen carriers: how much methemoglobin is too much?
R. Linberg (1998)
10.1074/jbc.273.48.31731
A Causative Role for Redox Cycling of Myoglobin and Its Inhibition by Alkalinization in the Pathogenesis and Treatment of Rhabdomyolysis-induced Renal Failure*
K. Moore (1998)
10.1016/0167-4838(95)00017-O
Effects of polymerization on the oxygen carrying and redox properties of diaspirin cross-linked hemoglobin.
M. Rogers (1995)
10.3109/10731199809118943
Hemoglobin autooxidation/oxidation mechanisms and methemoglobin prevention or reduction processes in the bloodstream. Literature review and outline of autooxidation reaction.
B. Faivre (1998)
10.1006/BBRC.1998.9312
Autoxidation of pyridoxalated hemoglobin polyoxyethylene conjugate.
T. Talarico (1998)
10.1152/JAPPL.1993.74.4.1769
Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin.
J. Hess (1993)
physiology, pathophysiology and pharmacology
S. Moncada (1991)
10.1016/S1357-4310(95)80089-1
Hemoglobin and free radicals: implications for the development of a safe blood substitute.
A. Alayash (1995)
The mechanism of metmyoglobin oxidation.
King Nk (1963)
Free radicals in the vasculature—the good, the bad, and the ugly. Biochemist (Bulletin of the Biochemical Society
V. W. Darley-Usmar (1994)
how much methemoglobin is too much? Artif
R. Linberg (1998)
10.1074/JBC.274.4.2029
Reactions of Sperm Whale Myoglobin with Hydrogen Peroxide
A. Alayash (1999)
Polyethylene glycol-modified liposome-encapsulated hemoglobin: a long circulating red cell substitute.
W. Phillips (1999)
10.1152/AJPHEART.1995.269.2.H648
Oxidative-stress response in vascular endothelial cells exposed to acellular hemoglobin solutions.
R. Motterlini (1995)
evaluation of renal toxicity
R. Lee (1989)
10.1097/00003246-199709000-00014
Initial evaluation of diaspirin cross-linked hemoglobin (DCLHb) as a vasopressor in critically ill patients.
G. Reah (1997)
10.1152/ajpheart.1999.277.1.H92
Detection of a ferrylhemoglobin intermediate in an endothelial cell model after hypoxia-reoxygenation.
L. L. McLeod (1999)
10.1039/A702483E
Free radical in blood: a measure of haemoglobin autoxidation in vivo?†
D. Svistunenko (1997)
10.1152/ajpheart.1998.275.3.H1046
Acellular hemoglobin-mediated oxidative stress toward endothelium: a role for ferryl iron.
D. W. Goldman (1998)



This paper is referenced by
10.1002/BP0700298
Hemoglobin-Based O2Carrier O2Affinity and Capillary Inlet pO2Are Important Factors That Influence O2Transport in a Capillary
Michael L Dimino (2007)
Impact of halal slaughtering on quality and shelf-life of broiler chicken meat
A. Addeen (2014)
10.1517/14712598.3.3.509
The use of haemoglobin glutamer-250 (HBOC-201) as an oxygen bridge in patients with acute anaemia associated with surgical blood loss
J. Levy (2003)
10.2174/157016312802650797
ATP-adenosine-glutathione cross-linked hemoglobin as clinically useful oxygen carrier.
J. Simoni (2012)
10.1007/4-431-26651-8_10
Hemoglobin-Vesicles (HbV) as Artificial Oxygen Carriers
H. Sakai (2005)
10.1111/j.1525-1594.2008.00695.x
Control of oxidative reactions of hemoglobin in the design of blood substitutes: role of the ascorbate-glutathione antioxidant system.
J. Simoni (2009)
10.3109/10731199.2010.501753
Physicochemical Characteristics of OxyVita Hemoglobin, a Zero-Linked Polymer: Liquid and Powder Preparations
J. Harrington (2011)
10.1517/14712598.1.1.121
O-raffinose-polymerised haemoglobin. A biochemical and pharmacological profile of an oxygen carrier
R. Scatena (2001)
10.1124/pr.108.000240
Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides
C. Wilcox (2008)
10.1016/j.ajem.2013.11.045
Resuscitation from hemorrhagic shock using polymerized hemoglobin compared to blood.
D. Ortiz (2014)
10.1016/S0003-2697(02)00233-6
Stopped-flow fluorescence method for the detection of heme degradation products in solutions of chemically modified hemoglobins and peroxide.
Y. Jia (2002)
Camel-Derived Haemoglobin , A New Blood Substitute and Oxygen Therapeutic
()
Role of Free Radicals in the Alterations of Immune Responses in Hemolytic Disorders
S. Gupta (2019)
10.1182/BLOOD-2005-09-3890
Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation.
K. Theilgaard-Mönch (2006)
10.1039/c6bm00046k
A biocompatible cobaltporphyrin-based complex micelle constructed via supramolecular assembly for oxygen transfer.
L. Shen (2016)
Investigation on artificial blood or substitute blood replace the natural blood
S. Keyhanian (2014)
10.1159/000049725
Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock
A. Pape (2001)
10.3171/JNS.2000.92.5.0899
Oxyhemoglobin and apoptosis.
F. D'agnillo (2000)
10.3390/biom7010002
Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help?
A. Alayash (2017)
10.1016/j.cbi.2015.05.021
Nitrite attenuated hypochlorous acid-mediated heme degradation in hemoglobin.
Naihao Lu (2015)
10.1002/0471266949.BMC048
Oxygen Delivery by Allosteric Effectors of Hemoglobin, Blood Substitutes, and Plasma Expanders
B. Campanini (2003)
10.1081/BIO-100001253
VASOCONSTRICTIVE RESPONSE OF RAT MESENTERIC ARTERIOLES FOLLOWING INFUSION OF CROSS-LINKED, POLYMERIZED, AND CONJUGATED HEMOGLOBIN SOLUTIONS
A. Caron (2001)
10.1080/15216540601188546
Allosteric effects on oxidative and nitrosative reactions of cell‐free hemoglobins
C. Bonaventura (2007)
10.1074/jbc.M111.228650
Mechanisms of Slower Nitric Oxide Uptake by Red Blood Cells and Other Hemoglobin-containing Vesicles*
I. Azarov (2011)
10.1007/978-3-642-40717-8_37
Vasoconstriction, Hypertension and Oxidative Toxicity are Regulated by Polymerized Hemoglobin Size
Brian M. Belcik (2013)
10.1007/978-3-642-40717-8_19
Recombinant Human Hb‐SOD Fusion Proteins
Marie Grey (2013)
10.1111/J.1778-428X.2004.TB00090.X
Approaches to the Engineering of Hemoglobin‐Based Oxygen Carriers
C. Fronticelli (2004)
10.1097/01.CCM.0000156295.48075.49
Influence of heme-based solutions on stress protein expression and organ failure after hemorrhagic shock*
D. Kubulus (2005)
10.1046/j.1365-2796.2003.01150.x
Current status of blood substitute research: towards a new paradigm
R. Winslow (2003)
10.1152/ajpheart.00303.2008
Polymerized bovine hemoglobin decreases oxygen delivery during normoxia and acute hypoxia in the rat.
D. Irwin (2008)
10.1111/j.1750-3841.2011.02393.x
Characterization of a 12 kDa thermal-stable antigenic protein in bovine blood.
J. Ofori (2011)
10.1111/j.1399-6576.2004.00475.x
Fluid resuscitation from severe hemorrhagic shock using diaspirin cross‐linked hemoglobin fails to improve pancreatic and renal perfusion
A. Pape (2004)
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