Supporting Tissue Oxygenation During Acute Surgical Bleeding Using A Perfluorochemical-Based Oxygen Carrier

  • Peter E. Keipert
  • N. Simon Faithfull
  • Duane J. Roth
  • JoAnn D. Bradley
  • Sanjay Batra
  • Philip Jochelson
  • Kathryn E. Flaim
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 388)

Abstract

Attempts to develop so-called “blood substitutes” have historically focused on three approaches: 1) acellular hemoglobin (Hb) solutions, 2) encapsulation of Hb, and 3) perfluorochemical emulsions. Work on Hb solutions first began over 100 years ago,1 by lysing red blood cells to extract the oxygen-carrying Hb molecules. For the past 60 years, efforts have concentrated on purifying the Hb from the contaminating stromal lipid,2 and on developing ways to crosslink or polymerize the Hb molecules3 to prevent them from splitting into dimers (i.e., half-molecules) which are rapidly filtered by the kidney. Based on the fact that free Hb has a very short intravascular persistence and is potentially toxic to the kidney,4 some investigators have used microencapsulation as a means to package the Hb inside sub-micron lipid-coated vesicles.5,6

Keywords

Surfactant Starch Hepatitis Ethyl Europe 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ponfick, E., 1875, Experimentelle Beitrage auf Lehre von der Transfusion.Virchows Arch. 62:273–335.CrossRefGoogle Scholar
  2. 2.
    Rabiner, S. F., Heibert, J. R., Lopas, H., and Friedman, L. FL, 1967, Evaluation of a stroma-free hemoglobin solution.J. Exp. Med.126:1127–1142.PubMedCrossRefGoogle Scholar
  3. 3.
    Mok, W., Chen, D., and Mazur, A., 1975, Cross-linked hemoglobin as potential plasma extenders.Fed. Proc.34:1458–1460.PubMedGoogle Scholar
  4. 4.
    Savitsky, J. P., Doczi, J., Black, J., and Arnold, J. D., 1978, A clinical safety trial of stroma-free hemoglobin.Clin. Pharmacol. Ther.23:73–80.PubMedGoogle Scholar
  5. 5.
    Djordjevich, L., and Miller, I. F., 1980, Synthetic erythrocytes from lipid encapsulated hemoglobin.Exp. Hematol.8:584–592.PubMedGoogle Scholar
  6. 6.
    Hunt, C. A., Burnette, R. R., MacGregor, R. D., Strubbe, A. E., Lau, D. T., Taylor, N., and Kawada, H., 1985, Synthesis and evaluation of a prototypal artificial red cell. Science230:1165–1168.PubMedCrossRefGoogle Scholar
  7. 7.
    Tremper, K. K., 1985, Preface. In:Perfluorochemical Oxygen Transport, Tremper, K. K., (ed), Little, Brown, & Co., Boston, p. xv.Google Scholar
  8. 8.
    Clark, L. C., and Gollan, R., 1966, Survival of mammals breathing organic liquids equilibrated with oxygen at atmospheric pressure. Science152:1755–1756.PubMedCrossRefGoogle Scholar
  9. 9.
    Geyer, R. P., Monroe, R. G., and Taylor, K., 1968, Survival of rats totally perfused with a perfluorocarbon-detergent preparation. In: Organ Perfusion and Preservation, Norman, J. V., Folkman, J., Hardison, L. E., Ridolf, L. E., and Veith, F. J., (eds), Appleton-Century-Crofts, New York, pp. 85–95.Google Scholar
  10. 10.
    Riess, J. G., 1991, Fluorocarbon-based in vivooxygen transport and delivery systems.Vox Sang. 61:225–239.PubMedCrossRefGoogle Scholar
  11. 11.
    Naito, R., and Yokoyama, K., 1978, Perfluorochemical blood substitutes Fluosol-43, Fluosol-DA 20% and 35%.Technical Information Bulletin SeriesTechnical Information Bulletin Series No. 5, The Green Cross Corporation, Osaka, Japan.Google Scholar
  12. 12.
    Roth, D. J., Keipert, P. E., Faithfull, N. S., Zuck, T. F., and Riess, J. G., 1994, Facilitating oxygen delivery in conjunction with hemodilution. United States Patent 5,344,393.Google Scholar
  13. 13.
    Faithfull, N. S., 1994, Mechanisms and efficacy of fluorochemical oxygen transport and delivery. Art. Cells, Blood Substit., Immob. Biotech. 22:181–197.CrossRefGoogle Scholar
  14. 14.
    Snyder, J. Y., 1987, Assessment of systemic oxygen transport. In: Oxygen Transport in the Critically III, Snyder, J. V., Pinsky, M. R., (eds), Year Book Medical Publishers, Chicago, pp. 179–198.Google Scholar
  15. 15.
    Keipert, P. E., Bradley, J. D., Faithfull, N. S., Hazard, D. Y., Spooner, M., Mackley, K. M., Rusheen, P. D., Batra, S., and Flaim, S. F., 1994, Effects of Oxygent™(perflubron emulsion) on 02transport in a dog model of hemodilution and surgical bleeding. FASEB J. 8:A901.Google Scholar
  16. 16.
    Cernaianu, A. C., Spence, R. K., Vasilidze, T. V., DelRossi, A. J., Carrig, T, White, P. F., Nathanson, M., Okonkwo, N., Wahr, J. A., Faithfull, N. S., Keipert, P. E., and Flaim, K. E., 1994, A safety study of a perfluorochemical emulsion, Oxygent™, in anesthetized surgical patients.Anesthesiology81: A397.CrossRefGoogle Scholar
  17. 17.
    Wahr, J. A., Trouwborst, A., Spence, R. K., Henney, C. P., Tremper, K. K., Cernaianu, A. C., Lau, W., Vasilidze, T. V., Faithfull, N. S., Flaim, K. E., and Keipert, P. E., 1994, A pilot study of the efficacy of an oxygen carrying emulsion,Oxygent™, in patients undergoing surgical blood loss.Anesthesiology81: A313.CrossRefGoogle Scholar
  18. 18.
    Newman, R. J., Podolsky, D., and Loeb, P., 1994, Bad Blood.U.S. News, June, pp. 68–78.Google Scholar
  19. 19.
    American College of Physicians Clinical Guideline, 1992, Practice strategies for elective red blood cell transfusion. Annals Intern. Med. 116:403–406.Google Scholar
  20. 20.
    Mercuriali, F., Inghilleri, G, Biffi, E., Colotti, M. T., and Vinci, A., 1991, Autologous Blood. A safe alternative for surgical patientsIstituto Ortopedico “Gaetano Pini”, Immunology & Transfusion Service, TransMedica Europe Ltd., pp. 1–30.Google Scholar
  21. 21.
    Keipert, P. E., 1995, Use of Oxygent, a perfluorochemical-based oxygen carrier, as an alternative to intraoperative blood transfusion. Artif. Cells, Blood Substit., Immob. Biotech.23: (in press).Google Scholar
  22. 22.
    Keipert, P. E., Faithfull, N. S., Bradley, J. D., Hazard, D. Y., Hogan, J., Levisetti, M. S., and Peters, R. M., 1994, Enhanced oxygen delivery by perflubron emulsion during acute hemodilution. Artif. Cells, Blood Substit., Immob. Biotech. 22: 1161–1167.CrossRefGoogle Scholar

Copyright information

© Plenum Press,New York 1996

Authors and Affiliations

  • Peter E. Keipert
    • 1
  • N. Simon Faithfull
    • 1
  • Duane J. Roth
    • 1
  • JoAnn D. Bradley
    • 1
  • Sanjay Batra
    • 1
  • Philip Jochelson
    • 1
  • Kathryn E. Flaim
    • 1
  1. 1.Alliance Pharmaceutical CorporationSan DiegoUSA

Personalised recommendations