The development of hemoglobin solutions as red cell substitutes: Hemoglobin solutions

Gould, S

doi:10.1016/0955-3886(95)90081-0

Cited by 4 publications

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“…PolyHb can be heat sterilized and stored for 1 year even at room temperature ( Kim and Greenburg 2014 , Gould et al 1995 ). However, polyHb-SOD-CAT-CA contains both Hb and enzymes, and enzymes are particularly sensitive to storage and heat.…”

Section: Resultsmentioning

confidence: 99%

“…There was no initial interest in this until the 1989 crisis of HIV-contaminated blood. It took 20 years to develop this and other modified Hb oxygen carriers for clinical trials ( Gould et al 1995 , Chang 1997 , Klein 2000 , Winslow 2006 , Chang 2005 , Chang 2007 , Jahr et al 2008 , Chang 2013 , Burhop and Estep 2001 , Natanson et al 2008 , Moore et al 2009 , Biro et al 1995 ). It was too late for many patients infected with HIV from contaminated donor blood.…”

Section: Introductionmentioning

confidence: 99%

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A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

Bian

Chang

2014

Artificial Cells, Nanomedicine, and Biotechnology

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We crosslink hemoglobin (Hb), superoxide dismutase (SOD), catalase (CAT), and carbonic anhydrase (CA) to form a soluble polyHb-SOD-CAT-CA nanobiotechnological complex. The obtained product is a soluble complex with three enhanced red blood cell (RBC) functions and without blood group antigens. In the present study, 2/3 of blood volume was removed to result in 90-min hemorrhagic shock at mean arterial blood pressure (MAP) of 30 mmHg. This was followed by the reinfusion of different resuscitation fluids, then followed for another 60 min. PolyHb-SOD-CAT-CA maintained the MAP at 87.5 ± 5 mmHg as compared with 3 volumes of lactated Ringer’s solution, 43.3 ± 2.8 mmHg; blood, 91.3 ± 3.6 mmHg; polyHb-SOD-CAT, 86.0 ± 4.6 mmHg; poly stroma-free hemolysate (polySFHb), 85.0 ± 2.5 mmHg; and polyHb, 82.6 ± 3.5 mmHg. PolyHb-SOD-CAT-CA was superior to the blood and other fluids based on the following criteria. PolyHb-SOD-CAT-CA reduced tissue pCO2 from 98 ± 4.5 mmHg to 68.6 ± 3 mmHg. This was significantly (p < 0.05) more effective than lactated Ringer’s solution (98 ± 4.5 mmHg), polyHb (90.1 ± 4.0 mmHg), polyHb-SOD-CAT (90.9 ± 1.4 mmHg), blood (79.1 ± 4.7 mmHg), and polySFHb (77 ± 5 mmHg). PolyHb-SOD-CAT-CA reduced the elevated ST level to 21.7 ± 6.7% and is significantly (< 0.05) better than polyHb (57.7 ± 8.7%), blood (39.1 ± 1.5%), polySFHb (38.3% ± 2.1%), polyHb-SOD-CAT (27.8 ± 5.6%), and lactated Ringer’s solution (106 ± 3.1%). The plasma cardiac troponin T (cTnT) level of polyHb-SOD-CAT-CA group was significantly (P < 0.05) lower than that of all the other groups. PolyHb-SOD-CAT-CA reduced plasma lactate level from 18 ± 2.3 mM/L to 6.9 ± 0.3 mM/L. It was significantly more effective (P < 0.05) than lactated Ringer’s solution (12.4 ± 0.6 mM/L), polyHb (9.6 ± 0.7 mM/L), blood (8.1 ± 0.2 mM/L), polySFHb (8.4 ± 0.1 mM/L), and polyHb-SOD-CAT (7.6 ± 0.3 mM/L). PolyHb-SOD-CAT-CA can be stored for 320 days at room temperature. Lyophilized poly-Hb-SOD-CAT-CA can be heat pasteurized at 68F for 2 h. This can be important if there is a need to inactivate human immunodeficiency virus, Ebola virus, and other infectious organisms.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

Bian

Chang

2014

Artificial Cells, Nanomedicine, and Biotechnology

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“…The average molecular weights (AMW) are taken from published values [8][9][10][11] except for Polyheme. While the AMW for Polyheme was reported as 150 kD, with a molecular weight range up to 400 kD [12], these values were taken prior to implementation of process changes to further reduce tetrameric haemoglobin components [13]. Given that residual tetramer levels in Polyheme are considerably less than those in Hemopure (1% versus 3%) [11,13], the AMW of Polyheme formulations evaluated clinically was probably greater than that of Hempure (250 kD) but less than the upper range previously reported (400 kD).…”

Section: Summary Of Clinical Datamentioning

confidence: 99%

Haemoglobin-based oxygen carriers and myocardial infarction

Estep

2019

Artificial Cells, Nanomedicine, and Biotechnology

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The incidence of investigator diagnosed myocardial infarction (MI) is greater in patients treated with haemoglobin-based oxygen carriers (HBOCs) than controls. Clinical trials and literature pertaining to possible HBOC toxicity mechanisms have been analyzed in order to identify possible reasons for this imbalance. MI diagnosis is hampered by potential interference of troponin assays by haemoglobin, haemolysis and bilirubin. Nevertheless, insofar as the reported incidence correlates with actual occurrence, there is a positive relationship between MI and HBOC dose and size. Preclinical and clinical data suggest that direct cardiac toxicity and coronary vasoconstriction are unlikely. More probable are detrimental intravascular interactions between HBOCs and components of the coagulation cascade, particularly dysfunctional endothelium. Elucidation of mechanisms is impeded by a lack of clinical data. Measurement of relevant biomarkers would be extremely useful in this regard and in improving patient selection criteria. Conduct of clinical trials in carefully selected patient populations after the development of improved protocols for MI diagnosis, along with concomitant biomarker data collection, is recommended.

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“…It has been recognized for over 40 years that clearance of SFH is caused by dissociation of extracellular hemoglobin into dimers when diluted in plasma [2,6,7]. Hb dimers are small enough to pass through the glomerulus of the nephrons in the kidneys and may play a role in acute renal toxicity due to rapid oxidation, heme loss, and precipitation [13][14][15][16]. Crosslinking, polymerization and increasing the overall molecular weight of SFH has been carried out to reduce tetramer dissociation, increase circulation half-life, and reduce rates of autooxidation, heme loss, and precipitation [1,14,17].…”

Section: Introduction and Background Introductionmentioning

confidence: 99%

Enhancing stability and expression of recombinant human hemoglobin in E. coli: Progress in the development of a recombinant HBOC source

Graves

Henderson

Horstman

et al. 2008

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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The commercial feasibility of recombinant human Hb (rHb) as an O(2) delivery pharmaceutical is limited by the production yield of holoprotein in E. coli. Currently the production of rHb is not cost effective for use as a source in the development of third and fourth generation Hb-based oxygen carriers (HBOCs). The major problems appear to be aggregation and degradation of apoglobin at the nominal expression temperatures, 28-37 degrees C, and the limited amount of free heme that is available for holohemoglobin assembly. One approach to solve the first problem is to inhibit apoglobin precipitation by a comparative mutagenesis strategy to improve apoglobin stability. alpha Gly15 to Ala and beta Gly16 to Ala mutations have been constructed to increase the stability of the alpha helices of both subunits of HbA, based on comparison with the sequences of the more stable sperm whale hemoglobin subunits. Fetal hemoglobin is also known to be more stable than human HbA, and sequence comparisons between human beta and gamma (fetal Hb) chains indicate several substitutions that stabilize the alpha1beta1 interface, one of which, beta His116 to Ile, increases resistance to denaturation and enhances expression in E. coli. These favorable effects of enhanced globin stability can be augmented by co-expression of bacterial membrane heme transport systems to increase the rate and extent of heme uptake through the bacterial cell membranes. The combination of increased apoglobin stability and active heme transport appear to enhance holohemoglobin production to levels that may make rHb a plausible starting material for all extracellular Hb-based oxygen carriers.

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The development of hemoglobin solutions as red cell substitutes: Hemoglobin solutions

Cited by 4 publications

References 0 publications

A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

A novel nanobiotherapeutic poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] with no cardiac toxicity for the resuscitation of a rat model with 90 minutes of sustained severe hemorrhagic shock with loss of 2/3 blood volume

Haemoglobin-based oxygen carriers and myocardial infarction

Enhancing stability and expression of recombinant human hemoglobin in E. coli: Progress in the development of a recombinant HBOC source

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