Seminars in Hematology
Volume 44, Issue 1 , Pages 51-59 , January 2007

Red Cell Substitutes

  • Robert M. Winslow

      Affiliations

    • Corresponding Author InformationAddress correspondence to Robert M. Winslow, MD, Sangart, Inc, 6175 Lusk Blvd, San Diego, CA 92121.

References 

  1. Winslow R. Historical background. In:  Winslow R editors. Blood Substitutes. London: Elsevier; 2006;p. 5–16
  2. Thomas T. The intravenous injection of milk as a substitute for the transfusion of blood. NY State J Med. 1878;27:449–465
  3. Brinton J. The transfusion of blood and the intravenous injection of milk. Med Record. 1878;14:344–347
  4. In:  Winslow RM editors. Blood Substitutes. London: Elsevier; 2006;
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  23. Gould S, Moore E, Hoyt D, Burch JM, Haenel JB, Garcia J, et al. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. J Am Coll Surg. 1998;187:113–120
  24. Carson JL, Noveck H, Berlin JA, Gould SA. Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42:812–818
  25. Handrigan MT, Bentley TB, Oliver JD, Tabaku LS, Burge JR, Atkins JL. Choice of fluid influences outcome in prolonged hypotensive resuscitation after hemorrhage in awake rats. Shock. 2005;23:337–343
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  28. Winslow R, Chapman K. Pilot-scale preparation of hemoglobin solutions. Methods Enzymol. 1994;231:3–16
  29. Hess J, Macdonald V, Winslow R. Dehydration and shock: An animal model of hemorrhage and resuscitation of battlefield injury. Artif Cells Blood Substit Immobil Biotechnol. 1992;19:499–502
  30. Sloan EP, Koenigsberg M, Gens D, Cipolle M, Runge J, Mallory MN, et al. Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhagic shock (A randomized controlled efficacy trial). JAMA. 1999;282:1857–1864
  31. Saxena R, Wijnhoud AD, Carton H, Hacke W, Kaste M, Przybelski RJ, et al. Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke. 1999;30:993–996
  32. Winslow RM. αα-Crosslinked hemoglobin: Was failure predicted by preclinical testing?. Vox Sang. 2000;79:1–20
  33. Looker D, Abbott-Brown D, Cozart P, Durfee S, Hoffman S, Mathews A. A human recombinant haemoglobin designed for use as a blood substitute. Nature. 1992;356:258–260
  34. Doherty DH, Doyle MP, Curry SR, Vali RJ, Fattor TJ, Olson JS, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol. 1998;16:672–676
  35. Rohlfs RJ, Bruner E, Chiu A, Gonzales A, Gonzales ML, Magde D, et al. Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide. J Biol Chem. 1998;273:12128–12134
  36. Intaglietta M, Johnson P, Winslow R. Microvascular and tissue oxygen distribution. Cardiovasc Res. 1996;32:632–643
  37. Winslow R, Intaglietta M, Tsai A, Vandegriff K, Wettstein R. Autoregulation and vasoconstriction: Foundation for a new generation of blood substitutes. Blood. 2002;100:210;(abstr)
  38. McCarthy MR, Vandegriff KD, Winslow RM. The role of facilitated diffusion in oxygen transport by cell-free hemoglobins: implications for the design of hemoglobin-based oxygen carriers. Biophys Chem. 2001;92:103–117
  39. Acharya AS, Manjula BN, Smith P. Hemoglobin crosslinkers. New York: Albert Einstein College of Medicine of Yeshiva University; 1996;patent (5,585,484). 1-16
  40. Vandegriff KD, Malavalli A, Wooldridge J, Lohman J, Winslow RM. MP4, a new nonvasoactive PEG-Hb conjugate. Transfusion. 2003;43:509–516
  41. Bucci E, Matheson B, Kwansa H, Koehler R. Development of non-extravasating hemoglobin-based oxygen carriers. In:  Winslow R editors. Blood Substitutes. London: Elsevier; 2006;p. 488–497
  42. Matheson B, Razynska A, Kwansa H, Bucci E. Appearance of dissociable and cross-linked hemoglobins in the renal hilar lymph. J Lab Clin Med. 2000;135:459–464
  43. Nemoto M, Mito T, Brinigar W, Fronticelli C, Koehler RC. Salvage of focal cerebral ischemia damage by transfusion of high O2 affinity recombinant polymers in mouse. J Appl Physiol. 2006;100:1688–1691
  44. Winslow RM, Gonzales A, Gonzales M, Magde M, McCarthy M, Rohlfs RJ, et al. Vascular resistance and the efficacy of red cell substitutes in a rat hemorrhage model. J Appl Physiol. 1998;85:993–1003
  45. Winslow RM, Lohman J, Malavalli A, Vandegriff KD. Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J Appl Physiol. 2004;97:1527–1534
  46. Tsai A, Vandegriff K, Intaglietta M, Winslow R. Targeted O2 delivery by cell-free hemoglobin: a new basis for O2 therapeutics. Am J Physiol. 2003;285:H1411–H1419
  47. Tsai AG, Cabrales P, Manjula BN, Acharya S, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers. Blood. 2006;108:3603–3610
  48. Drobin D, Kjellstrom B, Malm E, Malavalli A, Lohman J, Vandegriff K, et al. Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4). J Appl Physiol. 2004;96:1843–1853
  49. Young M, Riddez L, Kjellstrom B, Bursell J, Winslow F, Lohman J, et al. MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med. 2005;33:1794–1804
  50. Burhop KE, Estep TE. Hemoglobin-induced myocardial lesions. Artif Cells Blood Substit Immobil Biotechnol. 2001;29:101;(abstr)
  51. Bjorkholm M, Fagrell B, Przybelski R, Winslow N, Young M, Winslow R. A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol. Haematologica. 2005;90:505–515
  52. Olofsson C, Ahl T, Johansson T, Larsson S, Nellgård P, Ponzer S, et al: A multi-center clinical study of the safety and activity of maleimide-polyethylene glycol hemoglobin (Hemospan) in patients undergoing major orthopedic surgery. Anesthesiology (in press)
  53. Silverman, T: Guidance for Industry: Criteria for Safety and Efficacy Evaluation of Oxygen Therapeutics as Red Cell Substitutes. http://www.fda.gov/cber/gdlns/oxytherbld.htm. Accessed November 2, 2006.
  54. Klein H. Transfusion medicine. In:  Winslow R editors. Blood Substitutes. London: Elsevier; 2006;p. 17–33
  55. Stehling L, Simon T. The red blood cell transfusion trigger (Physiology and clinical studies). Arch Pathol Lab Med. 1994;118:429–434
  56. Hess J, Macdonald V, Brinkley W. Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. J Appl Physiol. 1993;74:1769–1778
  57. Vandegriff K, McCarthy M, Rohlfs R, Winslow R. Colloid osmotic properties of modified hemoglobins: chemically cross-linked versus polyethylene glycol surface-conjugated. Biophys Chem. 1997;69:23–30

 Supported, in part, by NHLBI Grants No. HL-076163 and No. R01 HL62354 and by Sangart, Inc

PII: S0037-1963(06)00235-6

doi: 10.1053/j.seminhematol.2006.09.013

Seminars in Hematology
Volume 44, Issue 1 , Pages 51-59 , January 2007

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