Skip to main content
SpringerLink
Log in

Effects of Hemoglobin in Sepsis

  • Conference paper
Yearbook of Intensive Care and Emergency Medicine 1997

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 1997))

Abstract

Sepsis remains a major contributor to morbidity and mortality among the patient population of intensive care units [1]. Despite extensive research, treatment remains symptomatic and supportive. Clinically, sepsis in its hyperdynamic state is characterized by hypotension due to decreased systemic vascular resistance. The cardiac output is elevated in most cases of clinical sepsis. The vascular system is unresponsive to endogenous and exogenous catecholamines, myocardial contractility is decreased, and there is increased precapillary shunting manifesting itself as an increase in central venous oxygen saturation. As the syndrome worsens, a hypo-dynamic state follows, with circulatory shock and lactic acidosis secondary to tissue hypoxia, often leading to multiple organ dysfunction syndrome (MODS) and death.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anonymous (1990) Increase in National Hospital Discharge Survey rates for septicemia–United States, 1979–1987. MMWR–Morbidity Mortality Weekly Report 39: 31–34

    Google Scholar 

  2. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376

    Article  PubMed  CAS  Google Scholar 

  3. Furchgott RF (1988) Studies on relaxation of rabbit aorta by sodium nitrite: Basis for the proposal that the acid-activatable component of the inhibitory factor from retractor penis is inorganic nitrate and the endothelium-derived relaxing factor is nitric oxide. In: Van Houtte PM (ed) Mechanism of vasodilatation. Raven Press, New York, pp 401–414

    Google Scholar 

  4. Craven PA, DeRubertis FR (1978) Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J Biol Chem 253: 8433–8443

    PubMed  CAS  Google Scholar 

  5. Evans T, Carpenter A, Kinderman H, Cohen J (1993) Evidence of increased nitric oxide production in patients with the sepsis syndrome. Circ Shock 41: 77–81

    PubMed  CAS  Google Scholar 

  6. Barthlen W, Stadler J, Lehn NL, Miethke T, Bartels H, Siewert JR (1994) Serum levels of end products of nitric oxide synthesis correlate positively with tumor necrosis factor alpha and negatively with body temperature in patients with postoperative abdominal sepsis. Shock 2: 398–401

    Article  PubMed  CAS  Google Scholar 

  7. Fronticelli C, Karavitis M (1994) Reaction of nitric oxide with hemoglobin. Artif Cells Blood Substit Immobil Biotechnol 22: A99 (Abst)

    Google Scholar 

  8. Sharma VS, John ME, Waterman MR (1982) Functional studies on hemoglobin opossum. Conclusions drawn regarding the role of the distal histidine. J Biol Chem 257: 11887–11892

    PubMed  CAS  Google Scholar 

  9. Jia L, Bonaventura C, Bonaventura J, Stamler JS (1996) S-nitrosohaemoglobin–a dynamic activity of blood involved in vascular control. Nature 380: 221–226

    Article  PubMed  CAS  Google Scholar 

  10. Rioux F, Petitclerc E, Audet R, Drapeau G, Fielding RM, Marceau F (1994) Recombinant human hemoglobin inhibits both constitutive and cytokine-induced nitric oxide-mediated relaxation of rabbit isolated aortic rings. J Cardiovasc Pharmacol 24: 229–237

    PubMed  CAS  Google Scholar 

  11. Freas W, Llave R, Sing M, Hart J, McQuillan P, Muldoon S (1995) Contractile effects of diaspirin cross-linked hemoglobin (DCLHb) on isolated porcine blood vessels. J Lab Clin Med 125: 762–767

    PubMed  CAS  Google Scholar 

  12. Sharma AC, Gulati A (1994) Effect of diaspirin cross-linked hemoglobin and norepinephrine on systemic hemodynamics and regional circulation in rats. J Lab Clin Med 123: 299–308

    PubMed  CAS  Google Scholar 

  13. Katsuyama SS, Cole DJ, Drummond JC, Bradley K (1994) Nitric oxide mediates the hypertensive response to a modified hemoglobin solution (DCLHb) in rats. Artif Cells Blood Substit Immobil Biotechnol 22: 1–7

    Article  PubMed  CAS  Google Scholar 

  14. Schultz SC, Grady B, Cole F, Hamilton I, Burhop K, Malcolm DS (1993) A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin. J Lab Clin Med 122: 301–308

    PubMed  CAS  Google Scholar 

  15. Malcolm DS, Hamilton IN Jr, Schultz SC, Cole F, Burhop K (1994) Characterization of the hemodynamic response to intravenous diaspirin cross-linked hemoglobin solution in rats. Artif Cells Blood Substit Immobil Biotechnol 22: 91–107

    Article  PubMed  CAS  Google Scholar 

  16. Kida Y, Iwata S, Gyoutoku Y, Aikou A, Yamakawa T, Nishi K (1991) Vascular responsiveness to various vasoactive substances after exchange transfusion with pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) solution in anesthetized rats. Artif Organs 15: 5–14

    Article  PubMed  CAS  Google Scholar 

  17. Hess JR, Macdonald VW, Brinkley WW (1993) Systemic and pulmonary hypertension after resuscitation with cell-free hemoglobin. J Appl Physiol 74: 1769–1778

    PubMed  CAS  Google Scholar 

  18. Macdonald VW, Motterlini R (1994) Vasoconstrictor effects in isolated rabbit heart perfused with bis(3,5-dibromosalicyl)fumarate cross-linked hemoglobin (alpha alpha Hb). Artif Cells Blood Substit Immobil Biotechnol 22: 565–575

    Article  PubMed  CAS  Google Scholar 

  19. Biessels PT, Hak JB, Sleeker WK, van Beek JH, Bakker JC (1992) Effects of modified hemoglobin solutions on the isolated rabbit heart. Biomateri Artif Cells Immobil Biotechnol 20: 693–696

    CAS  Google Scholar 

  20. Yamakawa T, Miyauchi Y, Nishi K (1990) Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma-free hemoglobin on cardiac function in isolated rat heart. Artif Organs 14: 208–217

    Article  PubMed  CAS  Google Scholar 

  21. Looker D, Abbott-Brown D, Cozart P, et al (1992) A human recombinant haemoglobin designed for use as a blood substitute. Nature 356: 258–260

    Article  PubMed  CAS  Google Scholar 

  22. Fedorov NA, Iarochkin VS, Koziner VB, Khachaturian AA, Rozenberg GI (1978) Support of respiration and hemodynamics by complete blood replacement with artificial oxygen carriers: Polyhemoglobinalbumin and polyhemoglobin. Doklady Akademii Nauk SSSR 243: 1324–1326

    PubMed  CAS  Google Scholar 

  23. Chatterjee R, Welty EV, Walder RY, Pruitt SL, Rogers PH, Arnone A (1986) Isolation and characterization of a new hemoglobin derivative cross-linked between the alpha chains (lysine 99 alpha 1-lysine 99 alpha 2). J Biol Chem 261: 9929–9937

    PubMed  CAS  Google Scholar 

  24. DeVenuto F (1983) Modified hemoglobin solution as a resuscitation fluid. Vox Sang 44: 129–142

    Article  PubMed  CAS  Google Scholar 

  25. Yabuki A, Yamaji K, Ohki H, Iwashita Y (1990) Characterization of a pyridoxalated hemoglobinpolyoxyethylene conjugate as a physiologic oxygen carrier. Transfusion 30: 516–520

    Article  PubMed  CAS  Google Scholar 

  26. Malchesky PS, Takahashi T, Iwasaki K, Harasaki H, Nose Y (1990) Conjugated human hemoglobin as a physiological oxygen carrier–pyridoxalated hemoglobin polyoxyethylene conjugate (PHP). Artif Organs 13: 442–450

    CAS  Google Scholar 

  27. Kilbourn RG, Belloni P (1990) Endothelial coll production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst 82: 772–776

    Article  PubMed  CAS  Google Scholar 

  28. Bone HG, Schenarts PJ, Booke M, et al (1997) Pyridoxalated hemoglobin polyoxethylene conjugate normalizes the hyperdynamic circulation in septic sheep. Crit Care Med (In press)

    Google Scholar 

  29. Aranow JS, Wang H, Zhuang J, Fink MP (1996) Effect of human hemoglobin on systemic and regional hemodynamics in a porcine model of endotoxemic shock. Crit Care Med 24: 807–814

    Article  PubMed  CAS  Google Scholar 

  30. Sugi K, Newald J, Traber LD, et al (1991) Cardiac dysfunction after acute endotoxin administration in conscious sheep. Am J Physiol 260: H1474 - H1481

    PubMed  CAS  Google Scholar 

  31. Noshima S, Noda H, Herndon DN, Traber LD, Traber DL (1993) Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep. J Appl Physiol 74: 1528–1533

    PubMed  CAS  Google Scholar 

  32. Brady AJ, Poole Wilson PA, Harding SE, Warren JB (1992) Nitric oxide production within cardiac myocytes reduces their contractility in endotoxemia. Am J Physiol 263: H1963 - H1966

    PubMed  CAS  Google Scholar 

  33. Schulz R, Nava E, Moncada S (1992) Induction and potential biological relevance of a Ca(2 +)independent nitric oxide synthase in the myocardium. Br J Pharmacol 105: 575–580

    Article  PubMed  CAS  Google Scholar 

  34. Barriere SL, Lowry SF (1995) An overview of mortality risk prediction in sepsis. Crit Care Med 23: 376–393

    Article  PubMed  CAS  Google Scholar 

  35. Booke M, Hinder F, McGuire R, Traber LD, Traber DL (1996) Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Crit Care Med 24: 835–844

    Article  PubMed  CAS  Google Scholar 

  36. Chernow B, Rainey TG, Lake CR (1982) Endogenous and exogenous catecholamines in critical care medicine. Crit Care Med 10: 409–416

    Article  PubMed  CAS  Google Scholar 

  37. Chernow B, Roth BL (1986) Pharmacologic manipulation of the peripheral vasculature in shock: Clinical and experimental approaches. Circ Shock 18: 141–155

    PubMed  CAS  Google Scholar 

  38. Nelson S, Stewart RH, Traber L, Traber D (1991) Endotoxin-induced alterations in contractility of isolated blood vessels from sheep. Am J Physiol 260: H1790 - H1794

    PubMed  CAS  Google Scholar 

  39. Landin L, Lorente JA, Renes E, Canas P, Jorge P, Liste D (1994) Inhibition of nitric oxide synthesis improves the vasoconstrictive effect of noradrenaline in sepsis. Chest 106: 250–256

    Article  PubMed  CAS  Google Scholar 

  40. Hwang TL, Lau YT, Huang SF, Chen MF, Liu MS (1994) Changes of alpha 1-adrenergic receptors in human liver during intraabdominal sepsis. Hepatology 20: 638–642

    Article  PubMed  CAS  Google Scholar 

  41. Jones SB, Romano FD (1990) Myocardial beta adrenergic receptor coupling to adenylate cyclase during developing septic shock. Circ Shock 30: 51–61

    PubMed  CAS  Google Scholar 

  42. Carcillo JA, Litten RZ, Roth BL (1989) Norepinephrine-induced phosphorylation of a 25 kD phosphoprotein in rat aorta is altered in intraperitoneal sepsis. Circ Shock 28: 257–265

    PubMed  CAS  Google Scholar 

  43. Kilbourn RG, Joly G, Cashon B, DeAngelo J, Bonaventura J (1994) Cell-free hemoglobin reverses the endotoxin-mediated hyporesponsivity of rat aortic rings to alpha-adrenergic agents. Biochem Biophys Res Comm 199: 155–162

    Article  PubMed  CAS  Google Scholar 

  44. Bone HG, Schenarts PJ, Fischer SR, McGuire R, Traber LD, Traber DL (1997) Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep without effecting regional perfusion or organ function. Am J Physiol (In’press)

    Google Scholar 

  45. Cocks TM, Malta E, King SJ, Woods RL, Angus JA (1991) Oxyhatmoglobin increases the production of endothelin-1 by endothelial cells in culture. Eur J Pharmacol 196: 177–182

    Article  PubMed  CAS  Google Scholar 

  46. Theissen JL, Loick HM, Curry BB, Traber LD, Herndon DN, Traber DL (1991) Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep. J Appl Physiol 70: 2120–2125

    PubMed  CAS  Google Scholar 

  47. Nelson DP, Samsel RW, Wood LD, Schumacker PT (1988) Pathological supply dependence of systemic and intestinal OZ uptake during endotoxemia. J Appl Physiol 64: 2410–2419

    PubMed  CAS  Google Scholar 

  48. Bersten A, Sibbald WJ (1989) Circulatory disturbances in multiple systems organ failure. Crit Care Clin 5: 233–254

    PubMed  CAS  Google Scholar 

  49. Faraci FM, Brian JE Jr (1994) Nitric oxide and the cerebral circulation. Stroke 25: 692–703

    Article  PubMed  CAS  Google Scholar 

  50. Pelligrino DA, Koenig HM, Albrecht RF (1993) Nitric oxide synthesis and regional cerebral blood flow responses to hypercapnia and hypoxia in the rat. J Cereb Blood Flow Metab 13: 80–87

    Article  PubMed  CAS  Google Scholar 

  51. Meyer J, Hinder F, Stothert J Jr, Traber LD, Herndon DN, Flynn JT (1994) Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition. J Appl Physiol 76: 2785–2793

    PubMed  CAS  Google Scholar 

  52. Faraci FM (1991) Role of endothelium-derived relaxing factor in cerebral circulation: Large arteries vs. microcirculation. Am J Physiol 261: H1038 - H1042

    PubMed  CAS  Google Scholar 

  53. Booke M, Hinder F, McGuire R, Traber LD, Traber DL (1995) Cerebral perfusion in ovine sepsis treated with nitric oxide inhibition versus catecholamine. Anesth Analg 80: S50 (Abst)

    Google Scholar 

  54. Ueno M, Lee TJ (1993) Endotoxin decreases the contractile responses of the porcine basilar artery to vasoactive substances. J Cereb Blood Flow Metab 13: 712–719

    Article  PubMed  CAS  Google Scholar 

  55. Fish RE, Lang CH, Spitzer JA (1986) Regional blood flow during continuous low-dose endotoxin infusion. Circ Shock 18: 267–275

    PubMed  CAS  Google Scholar 

  56. Raper RF, Sibbald WJ, Hobson J, Rutledge FS (1991) Effect of PGE1 on altered distribution of regional blood flows in hyperdynamic sepsis. Chest 100: 1703–1711

    Article  PubMed  CAS  Google Scholar 

  57. Ferguson JL, Spitzer JJ, Miller HI (1978) Effects of endotoxin on regional blood flow in the un-anesthetized guinea pig. J Surg Res 25: 236–243

    Article  PubMed  CAS  Google Scholar 

  58. Lang CH, Bagby GJ, Ferguson JL, Spitzer JJ (1984) Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis. Am J Physiol 246: R331 - R337

    PubMed  CAS  Google Scholar 

  59. Mourelatos MG, Enzer N, Ferguson JL, Rypins EB, Burhop KE, Law WR (1996) The effects of di-aspirin cross-linked hemoglobin in sepsis. Shock 5: 141–148

    Article  PubMed  CAS  Google Scholar 

  60. Walker JF, Cumming AD, Lindsay RM, Solez K, Linton AL (1986) The renal response produced by nonhypotensive sepsis in a large animal model. Am J Kid Dis 8: 88–97

    PubMed  CAS  Google Scholar 

  61. Lübbesmeyer HJ, Woodson L, Traber LD, Flynn JT, Herndon DN, Traber DL (1988) Immunoreactive atrial natriuretic factor is increased in ovine model of endotoxemia. Am J Physiol 254: R567 - R571

    PubMed  Google Scholar 

  62. Redl G, Woodson L, Traber LD, et al (1992) Mechanism of immunoreactive atrial natriuretic factor release in an ovine model of endotoxemia. Circ Shock 38: 34–41

    PubMed  CAS  Google Scholar 

  63. Hinder F, Booke M, Traber LD, et al (1996) Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide. Crit Care Med 24: 131–136

    Article  PubMed  CAS  Google Scholar 

  64. Lingnau W, McGuire R, Dehring DJ, et al (1996) Changes in regional hemodynamics after nitric oxide inhibition during ovine bacteremia. Am J Physiol 270: R207 - R216

    PubMed  CAS  Google Scholar 

  65. Booke M, Hinder F, McGuire R, Traber LD, Traber DL (1996) Nitric oxide synthase inhibition versus norepinephrine in ovine sepsis: Effects on regional blood flow. Shock 5: 362–370

    Article  PubMed  CAS  Google Scholar 

  66. Martin CM, Sibbald WJ (1994) Modulation of hemodynamics and organ blood flow by nitric oxide synthase inhibition is not altered in normotensive, septic rats. Am J Respir Crit Care Med 150: 1539–1544

    PubMed  CAS  Google Scholar 

  67. Badr KF, Kelley VE, Rennke HG, Brenner BM (1986) Roles for thromboxane A2 and leukotrienes in endotoxin-induced acute renal failure. Kidney Int 30: 474–480

    Article  PubMed  CAS  Google Scholar 

  68. Tempel GE, Cook JA, Wise WC, Halushka PV, Corral D (1986) Improvement in organ blood flow by inhibition of thromboxane synthetase during experimental endotoxic shock in the rat. J Cardiovasc Pharmacol 8: 514–519

    Article  PubMed  CAS  Google Scholar 

  69. Nicolson AG, Haites NE, McKay NG, Wilson HM, MacLeod AM, Benjamin N (1993) Induction of nitric oxide synthase in human mesangial cells. Biochem Biophys Res Commun 193: 1269–1274

    Article  PubMed  CAS  Google Scholar 

  70. Shultz PJ, Tayeh MA, Marletta MA, Raij L (1991) Synthesis and action of nitric oxide in rat glomerular mesangial cells. Am J Physiol 261: F600 - F606

    PubMed  CAS  Google Scholar 

  71. Kvietys PR, McLendon JM, Bulkley GB, Perry MA, Granger DN (1982) Pancreatic circulation: intrinsic regulation. Am J Physiol 242: G596 - G602

    PubMed  CAS  Google Scholar 

  72. Breslow MJ, Miller CF, Parker SD, Walman AT, Traystman RJ (1987) Effect of vasopressors on organ blood flow during endotoxin shock in pigs. Am J Physiol 252: H291 - H300

    PubMed  CAS  Google Scholar 

  73. Hersch M, Gnidec AA, Bersten AD, Troster M, Rutledge FS, Sibbald WJ (1990) Histologic and ultrastructural changes in nonpulmonary organs during early hyperdynamic sepsis. Surgery 107: 397–410

    PubMed  CAS  Google Scholar 

  74. Meyer J, Hinder F, Stothert J, et al (1994) Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition. J Appl Physiol 76: 2785–2793

    PubMed  CAS  Google Scholar 

  75. Eldridge J, Russell R, Christenson R, et al (1996) Liver function and morphology after resuscitation from severe hemorrhage shock with hemoglobin solutions or autologous blood. Grit Care Med 24: 663–671

    Article  CAS  Google Scholar 

  76. Crowley JP, Metzger J, Gray A, Pivacek LE, Cassidy G, Valeri CR (1993) Infusion of stroma-free cross-linked hemoglobin during acute Gram-negative bacteremia. Circ Shock 41: 144–149

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. S. R. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. G. Bone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. L. Traber
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Clinical Director) (Clinical Director)

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Fischer, S.R., Bone, H.G., Traber, D.L. (1997). Effects of Hemoglobin in Sepsis. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine 1997. Yearbook of Intensive Care and Emergency Medicine, vol 1997. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-13450-4_36

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-13450-4_36

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-13452-8

  • Online ISBN: 978-3-662-13450-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation