Oxidative Protection of Hemoglobin and Hemerythrin by Cross-Linking with a Nonheme Iron Peroxidase: Potentially Improved Oxygen Carriers for Use in Blood Substitutes

2014 ◽  
Vol 15 (5) ◽  
pp. 1920-1927 ◽  
Author(s):  
Denisa Hathazi ◽  
Augustin C. Mot ◽  
Anetta Vaida ◽  
Florina Scurtu ◽  
Iulia Lupan ◽  
...  
Keyword(s):  
Blood Substitutes ◽  
Nonheme Iron ◽  
Cross Linking ◽  
Oxygen Carriers ◽  
Oxidative Protection

The biochemistry of drugs and doping methods used to enhance aerobic sport performance

2008 ◽  
Vol 44 ◽  
pp. 63-84 ◽  
Author(s):  
Chris E. Cooper
Keyword(s):  
Oxygen Uptake ◽  
Oxygen Content ◽  
Oxygen Delivery ◽  
Sport Performance ◽  
Blood Substitutes ◽  
Altitude Training ◽  
Blood Oxygen ◽  
Oxygen Carriers ◽  
Sports Performance ◽  
Blood Doping

Optimum performance in aerobic sports performance requires an efficient delivery to, and consumption of, oxygen by the exercising muscle. It is probable that maximal oxygen uptake in the athlete is multifactorial, being shared between cardiac output, blood oxygen content, muscle blood flow, oxygen diffusion from the blood to the cell and mitochondrial content. Of these, raising the blood oxygen content by raising the haematocrit is the simplest acute method to increase oxygen delivery and improve sport performance. Legal means of raising haematocrit include altitude training and hypoxic tents. Illegal means include blood doping and the administration of EPO (erythropoietin). The ability to make EPO by genetic means has resulted in an increase in its availability and use, although it is probable that recent testing methods may have had some impact. Less widely used illegal methods include the use of artificial blood oxygen carriers (the so-called ‘blood substitutes’). In principle these molecules could enhance aerobic sports performance; however, they would be readily detectable in urine and blood tests. An alternative to increasing the blood oxygen content is to increase the amount of oxygen that haemoglobin can deliver. It is possible to do this by using compounds that right-shift the haemoglobin dissociation curve (e.g. RSR13). There is a compromise between improving oxygen delivery at the muscle and losing oxygen uptake at the lung and it is unclear whether these reagents would enhance the performance of elite athletes. However, given the proven success of blood doping and EPO, attempts to manipulate these pathways are likely to lead to an ongoing battle between the athlete and the drug testers.

Oxygen Therapeutics: Pursuit of an Alternative to the Donor Red Blood Cell

2007 ◽  
Vol 131 (5) ◽  
pp. 734-741
Author(s):  
Paul M. Ness ◽  
Melissa M. Cushing
Keyword(s):  
Blood Donation ◽  
Blood Substitute ◽  
Blood Substitutes ◽  
Red Cells ◽  
Phase Iii ◽  
Red Cell ◽  
Oxygen Carriers ◽  
Term Survival ◽  
Phase Iii Clinical Trials ◽  
Human Red Blood Cells

Abstract Context.—There is no true substitute for the many functions of human red blood cells, and synthetic products will not replace the need for blood donation in the foreseeable future. Hemoglobin-based oxygen carriers have many characteristics that would serve as a useful adjunct to red cells in clinical settings. Over time, these technologies have the potential to dramatically reshape the practice of transfusion medicine. Objective.—To review the characteristics and potential utility of hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Several hemoglobin-based oxygen carriers are under study in phase III clinical trials. Novel uses for synthetic oxygen therapeutics are emphasized. Data Sources.—All published reports with the key words oxygen therapeutics, blood substitutes, and red cell substitutes from 1933 until March 2006 were searched through Medline. Significant findings were synthesized. Conclusions.—Recognition of the true impact of red cell substitutes is still several years away. The most compelling products, hemoglobin-based oxygen carriers, have potential use in trauma, providing immediate oxygen-carrying support in the face of alloantibodies or autoantibodies, and in other clinical situations in which long-term survival of red cells is not essential. In the interim, efforts should be focused on enhancing the current blood supply system while supporting ongoing and planned blood substitute research efforts, including trials assessing novel clinical indications for these products.

Abstract 190: Repeated Doses of Dodecafluoropentane Emulsion Provide Neuroprotection Up to 24 Hours Following Cerebral Artery Occlusion in Rabbits

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sean D Woods ◽  
Robert D Skinner ◽  
Aliza T Brown ◽  
Aaron M Ricca ◽  
Jennifer L Johnson ◽  
...  
Keyword(s):  
Cerebral Artery ◽  
Oxygen Delivery ◽  
Infarct Volume ◽  
Rabbit Model ◽  
Artery Occlusion ◽  
Blood Substitutes ◽  
Hypoxic Cell ◽  
Oxygen Carriers ◽  
Repeated Doses ◽  
Cerebral Artery Occlusion

Introduction: Neuroprotective strategies in ischemic stroke include oxygen delivery to sustain penumbra and prevent hypoxic cell death. Hyperbaric oxygen, blood substitutes, and liquid fluorocarbon-based oxygen carriers have often failed in treatment of stroke and other ischemic disorders. Dodecafluoropentane emulsion (DDFPe, boiling point 29°C) shifts to quasi-gas phase at body temperature, which allows absorption and transportation of very high levels of oxygen. Exceptionally small particle size, 250-300 nm, may allow oxygen delivery even through occluded vessels, by diffusion into hypoxic tissue unreachable by whole blood. In a preliminary stroke study in rabbits, DDFPe reduced infarct volumes in all experimental groups by 80% or more. Hypothesis: Repeated doses of DDFPe can reduce infarct volume for up to 24 hours after permanent cerebral artery occlusion in rabbits. Methods: New Zealand White rabbits (N=55) received cerebral angiography from a femoral artery approach. Embolic microspheres (diameter=700-900 μm) were injected into the internal carotid artery, permanently occluding the middle cerebral and/or anterior cerebral arteries. Rabbits were randomly assigned to treatment groups and sacrifice times as in Table 1. In all treated groups, intravenous DDFPe dosing with a 2% w/v emulsion began at 1 hour post-embolization and was repeated every 90 minutes until sacrifice at either 7 or 24 hours post-embolization. Following sacrifice, infarcts were measured as a percent of brain volume using vital stains on brain sections. Results: Percent infarct volume means significantly decreased for all DDFPe treated groups compared with controls (Table 1). Conclusion: Intravenous DDFPe begun 1 hour after stroke onset protects the brain from ischemic injury in the rabbit model of permanent embolic stroke. Decreased infarct volumes represent salvaged brain tissue. This effect can be observed for 24 hours with repeated doses.

Glutaraldehyde effect on hemoglobin: evidence for an ion environment modification based on electron paramagnetic resonance and Mossbauer spectroscopies

1990 ◽  
Vol 68 (4) ◽  
pp. 813-818 ◽  
Author(s):  
Alain Chevalier ◽  
Didiers Guillochon ◽  
Naima Nedjar ◽  
Jean Marie Piot ◽  
Mokambes Waran Vijayalakshmi ◽  
...  
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Functional Properties ◽  
Oxygen Affinity ◽  
Blood Substitute ◽  
Blood Substitutes ◽  
Point Of View ◽  
Cross Linking ◽  
Redox Potentials ◽  
Paramagnetic Resonance ◽  
Electron Paramagnetic

Glutaraldehyde is a widely used reagent for hemoglobin cross-linking in blood substitutes research. However, hemoglobin polymerization by glutaraldehyde involves modifications of its functional properties, such as oxygen affinity, redox potentials, and autoxidation kinetics. The aim of this article is to investigate, by electron paramagnetic resonance and Mossbauer spectroscopies, the changes that occur in the iron environment after glutaraldehyde cross-linking. Spectrometric studies were performed with native hemoglobin and hemoglobin cross-linked as soluble and insoluble polymers. Spectrometry data comparison with glutaraldehyde-modified hemoglobin functional properties allows to interpret from a structural point of view that glutaraldehyde action occurs as a decrease of the O—N(F8His) distance, an increase of the Fe—N(F8His) bond length, and the decrease of the distal-side steric hindrance.Key words: hemoglobin, glutaraldehyde, Mossbauer spectroscopy, electron paramagnetic resonance, blood substitute.

Perfluorocarbons: recent developments and implications for neurosurgery

1996 ◽  
Vol 85 (2) ◽  
pp. 248-254 ◽  
Author(s):  
Damianos E. Sakas ◽  
Karl W. Whittaker ◽  
Robert M. Crowell ◽  
Nicholas T. Zervas
Keyword(s):  
Ventilatory Support ◽  
Air Embolism ◽  
Egg Yolk ◽  
Blood Substitutes ◽  
Oxygen Carriers ◽  
Content Type ◽  
Recent Developments ◽  
Wide Clinical Application ◽  
Diagnostic Applications ◽  
Injured Patients

✓ Over the last 30 years, perfluorocarbons (PFCs) have been extensively investigated as oxygen carriers. Early studies indicated that these compounds could be used as blood substitutes or protective agents against ischemia. Adverse characteristics such as instability, short intravascular half-life, and uncertainties concerning possible toxicity precluded wide clinical application. However, advances in PFC technology have led to the development of improved second-generation oxygen carriers that incorporate well-tolerated emulsifiers (egg-yolk phospholipids). The authors review recent developments in this field and consider the potential role of PFCs in future neurosurgical practice. Diagnostic applications could include their use to assess cerebral blood flow, local oxygen tension, and brain metabolism or to achieve enhanced imaging and precise staging of inflammatory, neoplastic, or vascular disease processes by means of computerized tomography, ultrasonography, and magnetic resonance studies. Therapeutic applications could include cerebral protection, an adjunctive role in radiotherapy of malignant brain tumors, protection against air embolism, the preservation of organs for transplantation, and ventilatory support in head-injured patients with compromised lung function. In addition, PFCs have been used successfully as a tool in ophthalmic microsurgery and potentially they could fulfill a similar role in microneurosurgery.

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