Peg-Hemoglobin:an Efficient Oxygen-Delivery System in the Rat Exchange Transfusion and Hypovolemic Shock Models

Nho, Kwang; Linberg, Rita; Johnson, Marie; Gilbert, Carl W.; Shorr, Robert G. L.

doi:10.3109/10731199409117913

Cited by 22 publications

(10 citation statements)

References 2 publications

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“…As a blood substitute, PEG-Hb has been shown to perform better than dextran 70 because it has the ability to deliver oxygen (19). Dogs that received dextran 70 showed a slight decline in MAP and elevated H R compared to the other experimental groups, typical of hemodilution in which the faster HR is a direct physiological response to compensate for diminished oxygen delivery (15,20).…”

Section: Discussionmentioning

confidence: 99%

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

et al. 1997

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This study was designed to determine the effect of polyethylene glycol (PEG) conjugation on stroma-free bovine hemoglobin. This was accomplished by examining the effects of unmodified stroma-free bovine hemoglobin (bovine Hb), PEG modified bovine hemoglobin (PEGHb) and dextran 70 on heart rate (HR), mean arterial pressure (MAP), gross renal morphology, blood chemistry, and hemoglobinuria development in conscious beagle dogs following a 30% exchange transfusion. Dogs were implanted with telemetric blood pressure probes and after 2 weeks underwent an isovolumic 30% blood volume exchange transfusion. Dogs treated with bovine Hb displayed a significant increase in MAP for 2 h following the exchange transfusion with no effect on HR. These animals exhibited significant levels of hemoglobinuria (>20% of infused dose) within 24 h. Histopathologically, all bovine Hb infused dogs displayed renal tubular vacuolization, with 2 dogs showing regions of tubular casts and tubular cell regeneration. PEG-Hb was shown to have a circulatory half-life of 58.3 * 2.4 h and caused no significant changes in MAP or HR throughout the study period. Dogs excreted less than 0.1% of infused PEG-Hb within 24 h and displayed only renal tubular epithelial cell vacuolization. Dextran 70 caused a slight but insignificant decrease in MAP, elevated the HR, and exhibited only slight renal vacuole formation. Blood chemistry remained essentially stable following exchange transfusion with all the test articles. The conjugation of PEG to hemoglobin greatly increased the parent protein's vascular retention while attenuating some of its less favorable attributes.

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Section: Discussionmentioning

confidence: 99%

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

et al. 1997

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“…This seems to decrease the tendency for the molecules to dissociate from tetramers to dimers and keeps renal toxicity down. Two companies are pursuing this technology, one with human hemoglobin, Apex Bioscience (polyoxyethylene human hemoglobin) and the other with bovine hemoglobin, Enzon (polyethylene glycol treated bovine hemoglobin) 16,17 . By using the lysine residues and attaching other bridging molecules, intramolecularly cross-linked stable tetramers of hemoglobin can be formed.…”

Section: " "mentioning

confidence: 99%

Oxygen Carriers ‐ What is Behind Us? What is Ahead?

Spiess

1999

Transfus Alt Transfus Med

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New emphasis is upon other complications of transfusion. The literature showing that transfusion of components containing white cells acts as a immunosuppressant is growing steadily [1][2][3][4][5][6][7][8][9] . In orthopedic and cardiac surgery, recent articles are suggesting that transfusion of allogeneic red cells with white cells present may increase the risk of infection up to 3.5 fold. This leads to a much greater morbidity and mortality as well as cost to the individual and society. Past thinking had been that autologous blood transfusion was relatively cost ineffective because of the rarity of viral infections. However, a new computer model of quality-adjusted-life-year (QALY), including the cost of immunosuppression, shows that autologous blood becomes very cost effective 5 . In Europe, a lay interest has focused on bovine spongiform encephalopathy and although no demonstrable cases

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“…Winslow et al . provided the initial evidence that Enzon PEGylated bovine Hb 11 did not increase mean arterial pressure in rats in 50% exchange transfusion 21 . Conversely all other non‐PEGylated Hbs tested in experimentally and in clinical trials were hypertensive.…”

Section: Introductionmentioning

confidence: 96%

“…The presence of molecular Hb in the plasma layer next to the endothelium also enhances the oxygen transport to the endothelium and the microvascular vessel wall, causing over‐oxygenation of the arteriolar microcirculation, triggering an autoregulatory response aimed at maintaining the oxygen supply to the tissue at normal levels. This effect can be controlled by increasing the molecular size of Hb by PEGylation or polymerization 11,12 …”

Section: Introductionmentioning

confidence: 99%

“…Conversely all other non‐PEGylated Hbs tested in experimentally and in clinical trials were hypertensive. The Enzon PEGylated bovine Hb 11 is distinct from the other blood substitutes because of its optimal plasma volume expansion properties and its high oxygen affinity. The Enzon protocol, a nonconservative PEGylation platform, and based on what we know now this could very well be a dissociated molecular species another early PEGylation protocol, is that of Ajinomoto, and it involves the formation of multiple intermolecular cross links using bifunctional PEG reagents between the pyridoxylated Hb tetramers.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of the polyethylene glycol‐hemoglobin structure to increase the efficiency of plasma expansion and O₂ carrying capacity

Acharya

Intaglietta²,

Tsai³

2007

Transfus Alt Transfus Med

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SUMMARY Polyethylene glycol (PEG) surface decoration of hemoglobin (Hb) is being developed as a design strategy for generating an oxygen carrier with optimal plasma expansion characteristics and maintenance of microvascular function. HexaPEGylated Hb using six copies of 5 kDa PEG provides excellent tissue perfusion when used to correct blood volume losses at a plasma concentration of 2 g Hb/dL (as compared with unPEGylated Hbs used at 6–9 g Hb/dL). Efficacy attained with limited concentration of Hb allows effective use of available Hb obtained from outdated blood. However, the high oxygen affinity of PEG‐Hb in combination with its low plasma concentration limits the effective oxygen delivery capacity, impacting tissue oxygenation. This problem can be remedied either by lowering oxygen affinity of PEG‐Hb or by increasing its concentration in the circulation. PEGylation of low oxygen affinity intramolecularly cross‐linked Hbs, for example αα‐fumaryl‐Hb, lowers oxygen affinity and modulating the pattern of PEGylation (size and number of PEG‐chains to lower the colloidal osmotic pressure of PEG‐Hb) reduces the tendency to dilute the PEG‐Hb concentration in circulation because of fluid shifts into the intravascular volume. Novel chemistry platforms for PEGylation set the stage for next generation lower oxygen affinity PEGylated Hbs that optimizes oxygen delivery and tissue perfusion.

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Peg-Hemoglobin:an Efficient Oxygen-Delivery System in the Rat Exchange Transfusion and Hypovolemic Shock Models

Cited by 22 publications

References 2 publications

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

Oxygen Carriers ‐ What is Behind Us? What is Ahead?

Modulation of the polyethylene glycol‐hemoglobin structure to increase the efficiency of plasma expansion and O₂ carrying capacity

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Peg-Hemoglobin:an Efficient Oxygen-Delivery System in the Rat Exchange Transfusion and Hypovolemic Shock Models

Cited by 22 publications

References 2 publications

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

Physiological Effect of Polyethylene Glycol Conjugation on Stroma‐Free Bovine Hemoglobin in the Conscious Dog After Partial Exchange Transfusion

Oxygen Carriers ‐ What is Behind Us? What is Ahead?

Modulation of the polyethylene glycol‐hemoglobin structure to increase the efficiency of plasma expansion and O2 carrying capacity

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Product

Resources

About

Modulation of the polyethylene glycol‐hemoglobin structure to increase the efficiency of plasma expansion and O₂ carrying capacity