Physico-chemical and pharmacological comparison of pyridoxylated hemoglobin bound to polyoxyethylene or polymerized by glutaraldehyde.
Two modified hemoglobin solutions were assessed using the same physico-chemical and pharmacological techniques. The first was prepared by covalent binding of monomethoxypolyoxyethylene (MPOE) 1.9 kDa to pyridoxylated hemoglobin (PLP-Hb). The resulting conjugate had a molecular size of 100 kDa (MPOE-PLP-Hb). The solution was cleared of non-fixed MPOE through ion exchange chromatography on Spherodex, thus bringing viscosity and oncotic pressure back to physiological values. The second was prepared by limited polymerization of pyridoxylated hemoglobin with glutaraldehyde (POLY-PLP-Hb). Tangential flow ultrafiltration achieved a satisfactory polymer/oligomer return. Quality controls showed no difference between the solutions. Total isovolemic exsanguinotransfusions in the rat did not help differentiate the two solutions. Hemorrhagic shock (80% of blood volume, rat) gave definitive survival for 8 of the 14 animals tested with MPOE-PLP-Hb (57%) but only 3 of the 8 animals tested with POLY-PLP-Hb (38%). None of the chemical approaches to reduce hemoglobin loss proved any more efficient than another, with the evaluation techniques employed.
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Faculty of Pharmacological and Biological Sciences, Nancy, France.
Mouelle
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Clerc
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Labrude
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Vigneron
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D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry*; D005976:Glutaral; D006454:Hemoglobins / Q000737:chemistry*; D008297:Male; D011092:Polyethylene Glycols; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D012771:Shock, Hemorrhagic / Q000628:therapy
D001802:Blood Substitutes; D006454:Hemoglobins; C030939:polyhemoglobin-pyridoxal-5-phosphate; D011092:Polyethylene Glycols; D011732:Pyridoxal Phosphate; D005976:Glutaral