Advertisement

Oxygen Affinity of Hemoglobin Solutions Modified by Coupling with NFPLP and the Effects on Tissue Oxygenation in the Isolated Perfused Rat Liver

  • J. van der Plas
  • W. K. Bleeker
  • A. de Vries-van Rossen
  • A. van Hamersveld
  • G. Rigter
  • J. A. Loos
  • J. C. Bakker
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 191)

Abstract

The use of a stroma-free hemoglobin solution as a plasma expander with oxygen transport capacity is limited due to two unfavourable properties: 1. An increased oxygen affinity, which is mainly caused by the loss of 2,3-diphosphoglycerate (2,3-DPG) from the central cavity of the hemoglobin tetramer, and 2. A shortened vascular retention time, which is mainly due to excretion of the dimeric form of hemoglobin through the kidneys (Bunn et al., 1969). The goal of our research project is to modify the hemoglobin molecule so that a normal oxygen affinity and vascular retention time are obtained. In order to change these intrinsic properties, organic phosphate molecules were coupled covalently in the central cavity. The binding of pyridoxal 5′-phosphate was the first modification that has been studied (Benesch et al., 1972; Bakker et al., 1983, in press). It was observed that this derivative has a decreased oxygen affinity, but the main product cannot be produced in yields higher than 25%, because the phosphate-containing 3 chain redistributes due to dissociation of the tetramer. The binding of another .phosphate, 2-nor-2-formylpyridoxal 5′-phosphate (NFPLP) could solve this problem, because it couples between both (3 chains (Benesch et al., 1975).

Keywords

Liver Perfusion Oxygen Affinity Perfusion Time Hemoglobin Solution Oxygen Dissociation Curve 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bakker, J. C., van der Plas, J., Bleeker, W. K., de Vries-van Rossen, A., Schoester, M., Brummelhuis, H. G. J., and Loos, J. A., 1983, Oxygen affinity of hemoglobin solutions modified by coupling to PLP or NFPLP and the effects on tissue oxygenation, in: “Oxygen transport to tissue — VI”, Plenum Press, New York, in press.Google Scholar
  2. Benesch, R. E., Benesch, R., Renthal, R. D., and Maeda, N., 1972, Affinity labeling of the polyphosphate binding site of hemoglobin, Biochemistry, 11:3576–3582.PubMedCrossRefGoogle Scholar
  3. Benesch, R., Benesch, R. E., Yung, S., and Edalji, R., 1975, Hemoglobin covalently bridged across the polyphosphate binding site, Biochem. Biophys. Res. Commun. 4, 63:1123–1129.CrossRefGoogle Scholar
  4. Benesch, R., and Benesch, R. E., 1981, Preparation and properties of hemoglobin modified with derivatives of pyridoxal, in: “Methods in Enzymology”, Vol. 76, p 147–159, Academic Press, New York.Google Scholar
  5. Benesch, R., Triner, L., Benesch, R. E., Kwong, S., and Verosky, M., 1984, Enhanced oxygen unloading by an interdimerically cross-linked hemoglobin in an isolated perfused rabbit heart, Proc. Natl. Acad. Sci. USA, 81:2941–2943.PubMedCrossRefGoogle Scholar
  6. Bunn, H. F., Esham, W. T., and Bull, R. W., 1969, The renal handling of hemoglobin. I. Glomerular filtration, J. Exp. Med., 129:909–924.PubMedCrossRefGoogle Scholar
  7. Diepenhorst, P., Sprokholt, R., and Prins, H. K., 1972, Removal of leucocytes from whole blood and erythrocytes suspension by filtration through cotton wool, Vox sang., 23:308–320.PubMedCrossRefGoogle Scholar
  8. Duvelleroy, M. A., Buckles, R. G., Rosenkaimer, S., Tung, S., and Laver, M. B., 1970, An oxyhemoglobin dissociation analyzer. J. Appl. Physiol., 28:227–233.PubMedGoogle Scholar
  9. Pocker, A., 1973, Synthesis of 2-nor-2-formylpyridoxal 5’-phosphate, a bifunctional reagens specific for the cofactor site in proteins, J. Org. Chem., 38:4295–4299.PubMedCrossRefGoogle Scholar
  10. Teisseire, B., Lousance, D., Soulard, C., Herigault, R., Teisseire, L., and Laurent, D., 1975, A method of continuous recording on micro-samples of the Hb-O2 association curve. I. Technique and direct registration of standard results, Bull. Europ. Physio-path. Resp., 11:837–851.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • J. van der Plas
    • 1
  • W. K. Bleeker
    • 1
  • A. de Vries-van Rossen
    • 1
  • A. van Hamersveld
    • 1
  • G. Rigter
    • 1
  • J. A. Loos
    • 1
  • J. C. Bakker
    • 1
  1. 1.Central Laboratory of the Netherlands Red Cross Blood Transfusion ServiceAmsterdamThe Netherlands

Personalised recommendations