The usefulness of hemoglobin solutions as oxygen transporters is limited by their high affinity for oxygen and rapid elimination from the circulation. Various chemical modifications of hemoglobin aimed at overcoming these two handicaps have been suggested. We have developed a conjugate of pyridoxylated human hemoglobin with monomethoxypolyoxyethylene 1900, whose preparation and properties are described. We present comparative results on short-term or definitive survival of Wistar rats which, during hemorrhagic shock due to the loss of 60 or 80% of their blood mass, were given a solution of native or modified hemoglobin, in some cases purified by ion-exchange chromatography to remove non-heme proteins, lipids, and some endotoxins. The more complex the treatment used to improve the properties and the purity of the hemoglobin solutions, the longer the animals survived. The loss of hemoglobin in the urine was greatly reduced after conjugation: after 20 h, less than 6% of the total infused.
Ajinomoto Co, Inc. Polyalkylene glycol-bound hemoglobins as blood substitutes. Japan Kokai Tokkyo Koho JP1984; 59: 104–323 (84: 104-323), Chem Abst 1984; 101, 381, 198230 v.
2.
AjisakaK., IwashitaY.Modification of human hemoglobin with polyethylene glycol: a new candidate for blood substitute. Biochem Biophys Res Commun1980; 97: 1076.
3.
BeneschR.E., BeneschR., RenthalR.D., MaedaN.Affinity labeling of the polyphosphate binding site of hemoglobin. Biochemistry1972; 11: 3576.
4.
DeloachJ.R., SheffieldC.L., SpatesG.E.A continuous-flow high-yield process for preparation of lipid-free hemoglobin. Anal Biochem1986; 157: 191.
5.
EvelynK.A., MalloyH.I.Microdetermination of oxyhemoglobin, methemoglobin and sulfhemoglobin in a single sample of blood. J Biol Chem1938; 126: 655.
6.
GreenburgA.G., SchooleyM., PeskinG.W.Improved retention of stroma-free hemoglobin solution by chemical modification. J Trauma1977; 17: 501.
7.
IwasakiK., IwashitaY.Preparation of hemoglobin-polyalkylene glycol complexes as blood substitutes. Japan Kokai Tokkyo Koho JP1986; 61: 53–223 (86: 53-223), Chem Abst 1986; 105, 379, 12188 s.
8.
IwasakiK., IwashitaY.Preparation and evaluation of hemoglobinpolyethylene glycol conjugate (pyridoxalated polyethylene glycol hemoglobin) as an oxygen-carrying resuscitation fluid. Artif Organs1986; 10: 411.
9.
IwasakiK., IwashitaY., IkedaK., VematsuT.Efficacy and safety of hemoglobin-polyethylene glycol conjugate (pyridoxalated polyethylene glycol hemoglobin) as an oxygen carrying resuscitation fluid. Artif Organs1986; 10: 470.
10.
IwashitaY., IwasakiK., AjisakaK., IkedaK., VematsuT.Use of a new oxygen-carrying blood substitute. Progr Artif Organs1983; 2: 867.
11.
IwashitaY., IwasakiK., YabukiA., GonshoA., OkamiT., KosakaK.Preparation and characteristic of stabilized hemoglobin. In: HoriM., NoséY., eds. International Symposium on stabilized hemoglobin.Cleveland: ISAO Press N° 309, 5, 1987.
12.
KeipertP.E., ChangT.M.S.Pyridoxalated polyhemoglobin as a red cell substitute for resuscitation of lethal hemorrhagic shock in conscious rats. Biomat Med Dev Artif Organs1985; 13: 1.
13.
LéonardM., NeelJ., DellacherieE.Synthesis of monomethoxypolyoxyethylene-bound haemoglobins. Tetrahedron1984; 40: 1581.
14.
LéonardM., DellacherieE.Acylation of human hemoglobin with polyoxyethylene derivatives. Biochim Biophys Acta1984; 791: 219.
15.
MatsuhitaM., IwashitaY., IwasakiK.Physiologic effects of pyridoxalated-hemoglobin-polyethylene glycol conjugate solution in exchange transfusions. Trans Amer Soc Artif Intern Organs1986; 32: 490.
16.
MenuP., PaulyF., LabrudeP., VigneronC.Hemoglobin pyridoxylation. Optimization and observation of an additional new PLP-Hb species by HPLC resolution. J Chromat1987; 417: 397.
17.
NishiK., YamakawaT., YanoK., OhtaT.Transfusion of polyoxyethylene conjugate of pyridoxalated human hemoglobin in dogs with hemorrhagic shock. Biomat Artif Cells Artif Organs1987; 15: 381.
18.
RabinerS.F., HelbertJ.R., LopasH., FriedmanL.H.Evaluation of a stroma-free hemoglobin solution for use as a plasma-expander. J Exp Med1967; 126: 1127.
19.
RinglerD.H., DabichL.Hematology and clinical biochemistry. In: BakerH.J., LindseyJ.R., WeisbrothS.H.J., eds. The laboratory rat, biology and diseases.New York: Acad Press, 1979; 105.
20.
SehgalL.R., RosenA.L., NoudG.Large-volume preparation of pyridoxylated hemoglobin with high P50. J Surg Res1981; 30: 14.
UccelliG.Le choc hémorragique expérimental. Utilisation de l'inhibiteur de Frey et approche d'un mécanisme d'action hémodynamique. Thèse Pharm Montpellier1978; 154.
