Vasoconstrictive Response of Rat Mesenteric Arterioles Following Infusion of Cross-Linked, Polymerized, and Conjugated Hemoglobin Solutions

Caron, Alexis; Malfatti, Emmanuelle; Aguejouf, Omar; Faivre-Fiorina, Béatrice; Menu, Patrick

doi:10.1081/bio-100001253

Cited by 14 publications

(15 citation statements)

References 21 publications

(25 reference statements)

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“…There have been considerable discussions on the reasons why infusion of most hemoglobin-based blood substitutes result in increased vasoactivity whereas a few others do not [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. One proposal is that the tetrameric hemoglobin component transverses the intercellular junction of the endothelial cell lining and binds nitric oxide from the interstitial space needed for normal vasodilatation [3][4][5]9,10,14].…”

Section: Introductionmentioning

confidence: 99%

Polyhemoglobin with Different Percentage of Tetrameric Hemoglobin and Effects on Vasoactivity and Electrocardiogram

Liu

Chang

2006

Artificial Cells, Blood Substitutes, and Biotechnology

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There has been considerable discussions on why some types of haemoglobin-based blood substitutes increase vasoactivity whereas a very few others do not. In this study, we prepare four different types of PolyHb each containing different percentage of tetrameric hemoglobin using glutaraldehyde crosslinking and characterized to ensure that they all have the same oxygen affinity. Thus the preparations are prepared from the same chemical method and have the same oxygen affinity. We infused these in the form of 1/6 volume toploading into anesthetized rats to simulate the use of blood substitutes in surgery. Mean arterial pressure (MAP) increased immediately after injection of PolyHb containing 38% or 78% of tetrameric hemoglobin. However, there was no significant increase in blood pressure with the injection of PolyHb containing 16% or 0.4% tetrameric hemoglobin. In electrocardiogram (ECG) study, we observe that high percentage (78%) of tetrameric hemoglobin causes marked changes in ECG immediately after infusion. Injection of PolyHb containing 16% or 38% of tetrameric hemoglobin resulted in minimal elevation of the ST segment. Infusion of PolyHb containing 0.4% of tetrameric hemoglobin did not result in any changes.

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Section: Introductionmentioning

confidence: 99%

Polyhemoglobin with Different Percentage of Tetrameric Hemoglobin and Effects on Vasoactivity and Electrocardiogram

Liu

Chang

2006

Artificial Cells, Blood Substitutes, and Biotechnology

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“…The system that bonds bovine Hb may result in problems of antigenicity on repeated usage [9]. Other conjugated Hbs like, dextran-benzene-tetracarboxylate-conjugated Hb (Hb-Dex-BTC), is undergoing animal trials [10].…”

Section: Polymer Conjugated Haemoglobinmentioning

confidence: 99%

“…Phase I trial studies conducted by Baxter in 1992 have revealed considerable success, excepting a dose-related elevation of blood pressure and decline in heart rate, corresponding to maximum dosage of 0.1 gm/Kg [1]. O'Hara et al observed an increase in whole blood methaemoglobin fraction (0.84 +/-0.77% at baseline to 4.08 +/-1.36%) during 48 hours of the DCL Hb infusion (dosage :936 +/-276 mg/Kg), but it did not reach a range associated with complications [10][11][12].…”

Section: Intramolecular Cross-linked Haemoglobinmentioning

confidence: 99%

“…The major concern pertains to the interference of Hb and its oxidation products with the vascular redox balance, potentially impeding its clinical usefulness. Endotoxin contaminants, residual cellular stroma, and lipid fragments are known mediators of toxicity leading to vasoconstriction, complement activation and generation of free radicals [1,10,14,15].…”

Section: Toxicitymentioning

confidence: 99%

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Artifical Blood

Goorha¹,

Deb²,

Chatterjee

et al. 2003

Medical Journal Armed Forces India

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Elimination of unwanted side-effects, especially transfusion-transmitted diseases (HIV and hepatitis) and leucocyte-mediated allosensitisation, is an important goal of modern transfusion medicine. The problems and high cost factor involved in collecting and storing human blood and the pending world-wide shortages are the other driving forces contributing towards the development of blood substitutes. Two major areas of research in this endeavour are haemoglobin-based oxygen carriers (HBOCs) and perfluorochemicals. Even though they do not qualify as perfect red blood cell substitutes, these 'oxygen carrying solutions' have many potential clinical and non clinical usages. These can reach tissues more easily than normal red cells and can deliver oxygen directly. These are not without adverse effects, and extensive clinical trials are being conducted to test their safety and efficacy. New understandings on the mode of action of these products will help to define their utility and application. Only after successful clinical trials can they be used for patient management, after approval by the FDA. MJAFI 2003; 59 : 45-50Key Words : Blood substitute; Haemoglobin solutions; Perfluorocarbons main advantages include availability in large volumes, storage for prolonged periods, rapid administration (without typing and cross matching) and sterilisation by pasteurisation. Their main known disadvantages are, reduced circulation half-life, haemodynamic and gastrointestinal perturbations, probably related to nitric oxide (NO) scavenging, free radical induction, and alterations of biochemical and haematological parameters (increase in liver enzyme levels, platelet aggregation) [1][2][3]. Purified haemoglobin solutionsThe first step in the pursuit for red cell substitute was

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“…Researchers found that some hemoglobin-based oxygen carriers caused transient systemic hypertension [78,79] and reduced cardiac output [80]. This is because large infusions of blood substitutes lower blood viscosity and the shear stress on the endothelium, which down-regulates the production of vasodilators by endothelial cells, causing vasoconstriction and increasing total peripheral vascular resistance [81]. In the hemorrhagic shock model, viscous blood substitutes limit vasoconstriction [82,83] and improve functional capillary density and oxygen content.…”

Section: Treatments That Increase Blood Viscositymentioning

confidence: 99%