Inhalation of Nitric Oxide in Severe ARDS

  • R. Rossaint
  • H. Gerlach
  • D. Pappert
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine 1994 book series (YEARBOOK, volume 1994)

Abstract

In 1980, Furchgott and Zawadski [1] reported the dependency of the relaxing effect of acetylcholine on the intact vascular endothelium. The authors postulated that the vasodilation must be mediated by an unstable humoral factor, later known as the endothelium-derived relaxing factor (EDRF). In 1987, two independent research groups published results which implied that nitric oxide (NO) accounts for the vasodilatatory action of EDRF [2, 3]. The generation of endogenous NO is a result of oxidation of one of the two terminal guanidino nitrogen atoms of L-arginine within the endothelial cells. Subsequent division of the oxidized L-arginine into NO and citrulline occurs [3, 4]. This process is calcium- and calmodulin-dependent, and is catalyzed by an enzyme termed “intrinsic” or “constitutive” NO synthase [5–7]; pulsatile flow characteristics [8] and shear stress [9] stimulate the generation of NO by this NO synthase. Due to the lipophilic characteristic of the formed NO, it rapidly diffuses from the vascular endothelium to vascular smooth muscles. In smooth muscle cells NO binds to the soluble guanulate cyclase, enhances the conversion of magnesium guanosine triphosphate into cyclic guanosine monophosphate (cGMP), and, thus, exerts a relaxing effect by the induction of dephosphorylation of myosin light chain filaments [10]. Whereas normal blood pressure homeostasis is dependent on this basal NO synthesis [11, 12], inappropriate vasodilation or shock may occur due to cytokine- or endotoxin-induced overproduction of NO [13–15] which then is produced by an isoform of the NO synthase, the “inducible” NO synthase.

Keywords

Syringe Interferon Prostaglandin Cytosol Acetylcholine 

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References

  1. 1.
    Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373–376PubMedCrossRefGoogle Scholar
  2. 2.
    Ignarro LJ; Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265–9269PubMedCrossRefGoogle Scholar
  3. 3.
    Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526PubMedCrossRefGoogle Scholar
  4. 4.
    Palmer RM, Rees DD, Ashton DS, Moncada S (1988) L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153: 1251–1256PubMedCrossRefGoogle Scholar
  5. 5.
    Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109–142PubMedGoogle Scholar
  6. 6.
    Mayer B, Schmidt K, Humbert R, Bohme E (1989) Biosynthesis of endothelium-derived relaxing factor: A cytosolic enzyme in porcine aortic endothelial cells Ca2 + dependently converts L-arginine into an activator of soluble guanylyl cyclase. Biochem Biophys Res Commun 164: 678–685PubMedCrossRefGoogle Scholar
  7. 7.
    Mulsch A, Bassenge E, Busse R (1989) Nitric oxide synthesis in endothelial cytosol: Evidence for a calcium-dependent and a calcium-independent mechanism. Naunyn-Schmiedeberg’s Arch Pharmacol 340: 767–770Google Scholar
  8. 8.
    Pohl U, Holtz J, Busse R, Bassenge E (1986) Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8: 37–44PubMedGoogle Scholar
  9. 9.
    Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 250: H1145 - H1149PubMedGoogle Scholar
  10. 10.
    Brenner BM, Troy JL, Ballermann BJ (1989) Endothelium-dependent vascular responses. Mediators and mechanisms. J Clin Invest 84: 1373–1378PubMedCrossRefGoogle Scholar
  11. 11.
    Rees DD, Palmer RMJ, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86: 3375–3378PubMedCrossRefGoogle Scholar
  12. 12.
    Vallance P, Collier J, Moncada S (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 2: 997–1000PubMedCrossRefGoogle Scholar
  13. 13.
    Kilbourn RG, Griffith OW (1992) Overproduction of nitric oxide in cytokine-mediated and septic shock. J Natl Cancer Inst 84: 827–831PubMedCrossRefGoogle Scholar
  14. 14.
    Ochoa JB, Curti B, Peitzman AB, et al (1992) Increased circulating nitrogen oxides after human tumor immunotherapy: Correlation with toxic hemodynamic changes. J Natl Cancer Inst 84: 864–867PubMedCrossRefGoogle Scholar
  15. 15.
    Hibbs JBJ, Westenfelder C, Taintor R et al (1992) Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest 89: 867–877PubMedCrossRefGoogle Scholar
  16. 16.
    Tomashefski JFJ, Davies P, Boggis C, Greene R, Zapol WM, Reid LM (1983) The pulmonary vascular lesions of the adult respiratory distress syndrome. Am J Pathol 112: 112–126PubMedGoogle Scholar
  17. 17.
    von Euler US, Liljestrand G (1946) Observations on the pulmonary arterial blood pressure in the cat. Acta Physiol Scand 12: 301–320CrossRefGoogle Scholar
  18. 18.
    Mitaka C, Hirata Y, Nagura T, Tsunoda Y, Amaha K (1993) Circulating endothelin-1 concentrations in acute respiratory failure. Chest 104: 476–480PubMedCrossRefGoogle Scholar
  19. 19.
    Erdmann AJ, Vaughan TRJ, Brigham KL, Woolverton WC, Staub NC (1975) Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep. Circ Res 37: 271–284PubMedGoogle Scholar
  20. 20.
    Gottlieb SS, Wood LD, Hansen DE, Long GR (1987) The effect of nitroprusside on pulmonary edema, oxygen exchange, and blood flow in hydrochloric acid aspiration. Anesthesiology 67: 203–210PubMedCrossRefGoogle Scholar
  21. 21.
    Sibbald WJ, Driedger AA, Myers ML, Short AI, Wells GA (1983) Biventricular function in the adult respiratory distress syndrome. Chest 84: 126–134PubMedCrossRefGoogle Scholar
  22. 22.
    Vlahakes GJ, Turley K, Hoffmann JI (1981) The pathophysiology of failure in acute right ventricular hypertension: Hemodynamic and biochemical correlations. Circulation 63: 87–95PubMedCrossRefGoogle Scholar
  23. 23.
    Radermacher P, Santak B, Becker H, Falke KJ (1989) Prostaglandin El and nitroglycerin reduce pulmonary capillary pressure but worsen ventilation-perfusion distributions in patients with adult respiratory distress syndrome. Anesthesiology 70: 601–606PubMedCrossRefGoogle Scholar
  24. 24.
    Zapol WM, Snider MT, Rie MA, Frikker M, Quinn DA (1985) Pulmonary circulation during adult respiratory distress syndrome. In: Zapol WM, Falke KJ (eds) Acute respiratory failure. Dekker, New York, pp 241–273Google Scholar
  25. 25.
    Hascheck WM, Reiser KM, Klein-Szanto AJ, et al (1983) Potentiation of butylated hydroxytoluene-induced acute lung damage by oxygen. Cell kinetics and collagen metabolism. Am Rev Respir Dis 127: 28–34Google Scholar
  26. 26.
    Kolobow T, Moretti MP, Fumagalli R, et al (1987) Severe impairment in lung function induced by high peak airway pressure during mechanical ventilation. An experimental study. Am Rev Respir Dis 135: 312–315PubMedGoogle Scholar
  27. 27.
    Higenbottam T, Pepke-Zaba J, Scott J, Woolman P, Coutts C, Wallwork J (1988) Inhaled “endothelium derived-relaxing factor” (EDRF) in primary hypertension. Am Rev Respir Dis 137: A107 (Abst)Google Scholar
  28. 28.
    Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM (1991) Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83: 2038–2047PubMedGoogle Scholar
  29. 29.
    Fratacci MD, Frostell CG, Chen TY, Wain JCJ, Robinson DR, Zapol WM (1991) Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 75: 990–999PubMedCrossRefGoogle Scholar
  30. 30.
    Pison U, Lopez FA, Heidelmeyer CF, Rossaint R, Falke K (1993) Inhaled nitric oxide selectively reverses hypoxic pulmonary vasoconstriction without impairing pulmonary gas exchange. J Appl Physiol 74: 1287–1292PubMedCrossRefGoogle Scholar
  31. 31.
    Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, Zapol WM (1993) Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation. Anesthesiology 78: 427–435PubMedCrossRefGoogle Scholar
  32. 32.
    Girard C, Lehot JJ, Pannetier JC, Filley S, French P, Estanove S (1992) Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension. Anesthesiology 77: 880–883PubMedCrossRefGoogle Scholar
  33. 33.
    Adnot S, Kouyoumdjian C, Defouilloy C, et al (1993) Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension. Am Rev Respir Dis 148: 310–316PubMedCrossRefGoogle Scholar
  34. 34.
    Roberts JD, Polander DM, Lang P, Zapol WM (1992) Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 818–819PubMedCrossRefGoogle Scholar
  35. 35.
    Kinsella JP, Neish SR, Shaffer E, Abman SH (1992) Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 819–820PubMedCrossRefGoogle Scholar
  36. 36.
    Levin DL, Heymann MA, Kitterman JA, Gregory GA, Phibbs RH, Rudolph AM (1976) Persistent pulmonary hypertension of the newborn infant. J Pediatr 89: 626–630PubMedCrossRefGoogle Scholar
  37. 37.
    Berner M, Beghetti M, Ricou B, Rouge JC, Pretre R, Friedli B (1993) Relief of severe pulmonary hypertension after closure of a large ventricular septic defect using low dose inhaled nitric oxide. Intensive Care Med 19: 75–77PubMedCrossRefGoogle Scholar
  38. 38.
    Sellden H, Winberg P, Gustafsson LE, Lundell B, Böök K, Frostell CG (1993) Inhalation of nitric oxide-reduced pulmonary hypertension after cardiac surgery in a 3.2-kg infant. Anesthesiology 78: 577–580PubMedCrossRefGoogle Scholar
  39. 39.
    Falke K, Rossaint R, Pison U, et al (1991) Inhaled nitric oxide selectively reduces pulmonary hypertension in severe ARDS and improves gas exchange as well as right heart ejection fraction: A case report. Am Rev Respir Dis 143 (Suppl): A248 (Abst)Google Scholar
  40. 40.
    Rossaint R, Falke KJ, Lopez F, Slama K, Pison U, Zapol WM (1993) Inhaled nitric oxide in adult respiratory distress syndrome. N Engl J Med 328: 399–405PubMedCrossRefGoogle Scholar
  41. 41.
    Wagner PD, Saltzman HA, West JB (1974) Measurement of continuous distributions of ventilation-perfusion ratios: Theory. J Appl Physiol 36: 588–599PubMedGoogle Scholar
  42. 42.
    Gerlach H, Rossaint R, Pappert D, Falke KJ (1993) Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome. Eur J Clin Invest 23: 499–502PubMedCrossRefGoogle Scholar
  43. 43.
    Slama K, Rossaint R, Keitel M, Lewandowski K, Steudel W, Falke K (1992) Effects of inhaled nitric oxide and IV prostacyclin on right ventricular function in patients with severe ARDS. Intensive Care Med (Suppl 2) 18: A110 (Abst)Google Scholar
  44. 44.
    Wysocki M, Vignon P, Roupie E, et al (1993) Improvement in right ventricular function with inhaled nitric oxide in patients with the adult respiratory distress syndrome (ARDS) and permissive hypercapnia. Am Rev Respir Dis 147: A350 (Abst)Google Scholar
  45. 45.
    Grover R, Smithies M, Bihari D (1993) A dose profile of the physiological effects of inhaled nitric oxide in acute lung injury. Am Rev Respir Dis 147: A350 (Abst)Google Scholar
  46. 46.
    Assreuy J, Cunha FQ, Liew FY, Moncada S (1993) Feedback inhibition of nitric oxide synthase activity by nitric oxide. Br J Pharmacol 108: 833–837PubMedGoogle Scholar
  47. 47.
    Rogers NE, Ignarro LJ (1992) Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. Biochem Biophys Res Commun 189: 242–249PubMedCrossRefGoogle Scholar
  48. 48.
    Payen D, Gatecel C, Guinard N (1992) Inhalation of low dose of NO and IV L-arginine in ARDS: Effect on pulmonary hemodynamic and gas exchange. Intensive Care Med 18 (Suppl 2 ) S66 (Abst)Google Scholar
  49. 49.
    Rovira I, Chen TY, Greene E, Zapol WM (1992) Combining inhaled nitric oxide (NO) and IV nitric oxide synthase (NOS) inhibition in an ovine lavage model of ARDS. Intensive Care Med 18 (Suppl 2 ) S67 (Abst)CrossRefGoogle Scholar
  50. 50.
    Austin AT (1967) The chemistry of the higher oxides of nitrogen as related to the manufacture, storage and administration of nitrous oxide. Br J Anaesth 39: 345–350PubMedCrossRefGoogle Scholar
  51. 51.
    Thomas HV, Mueller PK, Lyman RL (1968) Lipid peroxydation of lung lipids in rat exposed to nitrogen dioxyde. Science 159: 532–534PubMedCrossRefGoogle Scholar
  52. 52.
    Clutton-Brock J (1967) Two cases of poisoning by contamination of nitrous oxide with higher oxides of nitrogen during anaesthesia. Br J Anaesth 39: 388–392PubMedCrossRefGoogle Scholar
  53. 53.
    Greenbaum R, Bay J, Hargreaves MD, et al (1967) Effects of higher oxides of nitrogen on the anaesthetized dog. Br J Anaesth 39: 393–404PubMedCrossRefGoogle Scholar
  54. 54.
    Rasmussen TR, Kjaergaard SK, Tarp U, Pedersen OF (1992) Delayed effects of NO2 exposure on alveolar permeability and glutathione peroxidase in healthy humans. Am Rev Respir Dis 146: 654–659PubMedGoogle Scholar
  55. 55.
    Archer S (1993) Measurement of nitric oxide in biological models. FASEB J 7: 349–360PubMedGoogle Scholar
  56. 56.
    Karupiah G, Xie Q, Buller ML, Nathan C, Duarte C, MacMicking JD (1993) Inhibition of viral replication by interferon-y-induced nitric oxide synthase. Science 261: 1445–1448PubMedCrossRefGoogle Scholar
  57. 57.
    Nathan C (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J 6: 3051–3064PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • R. Rossaint
  • H. Gerlach
  • D. Pappert

There are no affiliations available

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