Cell-Free Hemoglobin Preserves Renal Function during Normothermic Ischemia

Whitley, David; Patterson, Robert B.; Greenburg, A. Gerson

doi:10.1006/jsre.1998.5375

Cited by 11 publications

(8 citation statements)

References 15 publications

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“…Fractional GFR and reabsorption increased (67). It has also been shown that perfusion with a cell‐free HBOC better preserves or restores renal blood flow and function following an acute ischemic renal event (67–69).…”

Section: Preclinical Safety (Toxicity) Studiesmentioning

confidence: 99%

Artificial Oxygen Carriers as Red Blood Cell Substitutes: A Selected Review and Current Status

2004

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Two distinct approaches are being explored in red blood cell substitute (RCS) development: hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbon-based oxygen carriers (PFBOCs). HBOCs are based on intra- and/or intermolecularly "engineered" human or animal hemoglobins (Hbs), optimized for O2 delivery and longer intravascular circulation. Some are currently being evaluated in Phase II/III clinical studies. PFBOCs are aqueous emulsions of perfluorocarbon derivatives that dissolve relatively large amounts of O2. A PFBOC based on a 60% (wt/vol) emulsion of perfluorooctyl bromide has been evaluated in Phase II/III clinical trials. Although current PFBOC products generally require patients to breathe O2 enriched air, they render certain advantages since they are totally synthetic. This article provides a short review of the basic principles, approaches, and current status of RCS development. Results of preclinical and clinical studies including recent Phase II/III clinical studies are discussed.

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Section: Preclinical Safety (Toxicity) Studiesmentioning

confidence: 99%

Artificial Oxygen Carriers as Red Blood Cell Substitutes: A Selected Review and Current Status

2004

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“…We could not find any morphologic changes in the kidneys in the sense of necrotic tubuli or sedimentation of proteins, which are often caused by free hemoglobin [25]. This probably shows the positive effect of the chemical modification of free hemoglobin with polyethylene glycol, which enables the normovolemic hemodilution of about 1/3 of the blood volume in our model without causing any severe damage.…”

Section: Discussionmentioning

confidence: 80%

Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on tissue necrosis in SKH1-hr hairless mice

Goertz

Kirschner²,

Lilienfein

et al. 2009

Eur J Med Res

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ObjectiveTissue hypoxia after blood loss, replantation and flap reperfusion remains a challenging task in surgery. Normovolemic hemodilution improves hemorheologic properties without increasing oxygen carrying capacity. Red blood cell transfusion is the current standard of treatment with its attendant risks. The aim of this study was to investigate the potential of the chemically modified hemoglobin, MP4, to reduce skin flap necrosis and its effect on selected blood markers and kidneys.Materials and methodsTissue ischemia was induced in the ear of hairless mice (n = 26). Hemodilution was performed by replacing one third of blood volume with the similar amount of MP4, dextran, or blood. The extent of non-perfused tissue was assessed by intravital fluorescent microscopy.ResultsOf all groups, MP4 showed the smallest area of no perfusion (in percentage of the ear ± SEM: 16.3% ± 2.4), the control group the largest (22.4% ± 3.5). Leukocytes showed a significant increase in the MP4 and dextran group (from 8.7 to 13.6 respectively 15.4*109/l). On histology no changes of the kidneys could be observed.ConclusionMP4 causes an increase of leukocytes, improves the oxygen supply of the tissue and shows no evidence of renal impairment.

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“…These carriers preserve the kidneys from functional disorders and destruction of cell structures [23]. In the pancreas haemoglobin-based oxygen carriers repair damages of the microcirculatory system caused by haemorrhagic shock [24].…”

Section: Discussionmentioning

confidence: 99%

Haemoglobin Hyperpolymers, a New Type of Artificial Oxygen Carrier – Concept and Current State of Development

Barnikol¹,

Poetzschke²

2004

Transfus Med Hemother

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In the clinical setting, artificial oxygen carriers are needed when a patient has a tissue oxygen deficiency which he/she cannot automatically compensate. There are two quite different situations where this might occur: i) Heavy blood loss (e.g. following an accident) and ii) insufficient perfusion (e.g. as a result of arteriosclerosis or myocardial infarction) or anaemia without blood loss. In the first instance, an iso-oncotic oxygen-transporting plasma expander is required, whereas in the second instance a (hypo-oncotic) so-called blood additive is needed. This 2nd type of situation also presents the greater range of very important indications. Experimental work has shown that, in comparison to erythrocytes, dissolved haemoglobin is able to release oxygen more rapidly (effective plasmatic transport) while at the same time also facilitating oxygen release from erythrocytes (mediator function). Blood additives occur naturally in lower forms of life (e.g. earthworm) where they can be found in the form of giant oxygen-carrying molecules. Using these natural forms as a basis, new oxygen-transporting blood additives were designed and developed (so-called haemoglobin hyperpolymers) which exhibit a strong oxygen affinity (half saturation partial pressure p₅₀ = 16 mm Hg) and high co-operativity (n₅₀ = 2.1). One product has, up to now, been produced aseptically on a small technical scale and consists of highly purified, polymerised and pegylated porcine haemoglobin which is free of monomers and oligomers (mean molecular weight approximately 800 kDa). It is sufficiently low in endotoxin (< 0.029 EU/ml) and blood plasma compatible and – at an effective concentration of 3 g/dl in blood plasma – causes only minor increases in oncotic pressure or viscosity. The product has a shelf life of up to 2 years and is administered as a carbonyl derivative. Its intravascular half-life in the conscious rat is 30 h. This product was found to prevent death in rats in wchich acute lung injury was induced using oleic acid. In human self-experiments this product was repeatedly administered: No effects on blood pressure and heart rate, no increase in blood transaminase concentration and no immunological reaction were seen; the latter was also true for selected sensitive mice. Furthermore, the blood additive is universally applicable as an oxygen transporter since, when mixed with a conventional plasma expander, it can also be used to treat an oxygen deficiency occurring together with blood loss.

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Cell-Free Hemoglobin Preserves Renal Function during Normothermic Ischemia

Cited by 11 publications

References 15 publications

Artificial Oxygen Carriers as Red Blood Cell Substitutes: A Selected Review and Current Status

Artificial Oxygen Carriers as Red Blood Cell Substitutes: A Selected Review and Current Status

Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on tissue necrosis in SKH1-hr hairless mice

Haemoglobin Hyperpolymers, a New Type of Artificial Oxygen Carrier – Concept and Current State of Development

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