Canadian Journal of Anesthesia

, Volume 50, Issue 8, pp 839–846

Inhaled nitric oxide in 2003: a review of its mechanisms of action

Neuroanesthesia and Intensive Care



To review the pulmonary and systemic effects of endogenous nitric oxide and inhaled nitric oxide administered to patients.


A systematic search for experimental data, human case reports, and randomized clinical trials since 1980, the year of discovery of endothelium-derived relaxing factor.

Principal findings

Nitric oxide has pulmonary and systemic effects. Inhaled nitric oxide not only causes selective pulmonary vasodilation but also results in pulmonary vasoconstriction of the vessels perfusing non-ventilated alveolae. The systemic effects of inhaled nitric oxide, which include modulation of the distribution of systemic blood flow, increase in renal output, interaction with coagulation, fibrinolysis and platelet functions, alteration of the inflammatory response, are described and the mechanisms of nitric oxide transport are explained. The possible toxicity of inhaled nitric oxide is also discussed.


The multiple effects of inhaled nitric oxide support its role as a pulmonary and extra-pulmonary medication.

L’inhalation de monoxyde d’azote en 2003: une revue de ses mécanismes et de son action



Revoir les effets pulmonaires et généraux de l’oxyde nitrique (NO) endogène et du NO inhalé, administré aux patients.


Une recherche systématique de données expérimentales, d’études de cas humains et d’essais cliniques randomisés réalisés depuis 1980, année de la découverte de ce facteur relaxant d’origine endothéliale, dénomination qui lui fût attribuée à l;époque.

Constatations principales

Le monoxyde d’azote a des effets pulmonaires et généraux. Le monoxyde d’azote inhalé ne cause pas seulement une vasodilatation pulmonaire sélective, mais il provoque aussi une vasoconstriction pulmonaire des vaisseaux perfusant les alvéoles non ventilées. Les effets généraux de monoxyde d’azote, y compris la modulation de la distribution du débit sanguin, l’augmentation du débit rénal, l’interaction avec la coagulation, la capacité fonctionnelle de la fibrinolyse et des plaquettes, la modification de la réponse inflammatoire, sont décrits et les mécanismes du transport de monoxyde d’azote sont expliqués. On discute également de la toxicité de monoxyde d’azote inhalé.


Les multiples effets de l’oxyde nitrique inhalé expliquent l’intérêt qu’il présente comme médication pulmonaire et extrapulmonaire.


  1. 1.
    Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987; 84: 9265–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002–12.PubMedCrossRefGoogle Scholar
  5. 5.
    Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994; 78: 915–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Tiefenbacher CP. Tetrahydrobiopterin: a critical cofactor for eNOS and a strategy in the treatment of endothelial dysfunction? Am J Physiol Heart Circ Physiol 2001; 280: H2484–8.PubMedGoogle Scholar
  7. 7.
    Blaise G. The endothelium at rest.In: Spiess (Ed.). The Relationship Between Coagulation, Inflammation, and Endothelium — A Pyramid Towards Outcome. Baltimore: Lippincott Williams & Wilkins; 2000: 31–78.Google Scholar
  8. 8.
    Kolesnikov YA, Pan YX, Babey AM, Jain S, Wilson R, Pasternak GW. Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: evidence for opposing NO actions on morphine analgesia and tolerance. Proc Natl Acad Sci USA 1997; 94: 8220–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Liu HW, Anand A, Bloch K, Christiani D, Kradin R. Expression of inducible nitric oxide synthase by macrophages in rat lung. Am J Respir Crit Care Med 1997; 156: 223–8.PubMedGoogle Scholar
  10. 10.
    Nussler AK, Billiar TR. Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 1993; 54: 171–8.PubMedGoogle Scholar
  11. 11.
    Guo FH, De Raeve HR, Rice TW, Stuehr DJ, Thunnissen FB, Erzurum SC. Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. Proc Natl Acad Sci USA 1995; 92: 7809–13.PubMedCrossRefGoogle Scholar
  12. 12.
    Belvisi MG, Stretton CD, Yacoub M, Barnes PJ. Nitric oxide is the endogenous neurotransmitter of bronchodilator nerves in humans. Eur J Pharmacol 1992; 210: 221–2.PubMedCrossRefGoogle Scholar
  13. 13.
    Lundberg JO, Lundberg JM, Settergren G, Alving K, Weitzberg E. Nitric oxide, produced in the upper airways, may act in an ‘aerocrine’ fashion to enhance pulmonary oxygen uptake in humans. Acta Physiol Scand 1995; 155: 467–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Chambers DC, Carpenter DA, Ayres JG. Exchange dynamics of nitric oxide in the human nose. J Appl Physiol 2001; 91: 1924–30.PubMedGoogle Scholar
  15. 15.
    Dillon WC, Hampl V, Shultz PJ, Rubins JB, Archer SL. Origins of breath nitric oxide in humans. Chest 1996; 110: 930–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Hogman M, Frostell CG, Hedenstrom H, Hedenstierna G. Inhalation of nitric oxide modulates adult human bronchial tone. Am Rev Respir Dis 1993; 148: 1474–8.PubMedGoogle Scholar
  17. 17.
    Lundberg JO, Settergren G, Gelinder S, Lundberg JM, Alving K, Weitzberg E. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans. Acta Physiol Scand 1996; 158: 343–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Francoe M, Troncy E, Blaise G. Inhaled nitric oxide: technical aspects of administration and monitoring. Crit Care Med 1998; 26: 782–96.PubMedCrossRefGoogle Scholar
  19. 19.
    Subhedar NV, Jauhari P, Natarajan R. Cost of inhaled nitric oxide therapy in neonates. Lancet 2002; 359: 1781–2.PubMedCrossRefGoogle Scholar
  20. 20.
    Lucas KA, Pitari GM, Kazerounian S, et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 2000; 52: 375–414.PubMedGoogle Scholar
  21. 21.
    Hanafy KA, Krumenacker JS, Murad F. NO, nitrotyrosine, and cyclic GMP in signal transduction. Med Sci Monit 2001; 7: 801–19.PubMedGoogle Scholar
  22. 22.
    Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovasc Res 1999; 43: 542–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Frostell C, Fratacci MD, Wain JC, Jones R, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 1991; 83: 2038–47.PubMedGoogle Scholar
  24. 24.
    Van Obbergh LJ, Charbonneau M, Blaise G. Combination of inhaled nitric oxide with i.v. nitroglycerin or with a prostacyclin analogue in the treatment of experimental pulmonary hypertension. Br J Anaesth 1996; 77: 227–31.PubMedGoogle Scholar
  25. 25.
    Alam MS, Akaike T, Okamoto S, et al. Role of nitric oxide in host defense in murine salmonellosis as a function of its antibacterial and antiapoptotic activities. Infect Immun 2002; 70: 3130–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Jain B, Rubinstein I, Robbins RA, Leise KL, Sisson JH. Modulation of airway epithelial cell ciliary beat frequency by nitric oxide. Biochem Biophys Res Commun 1993; 191: 83–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Ramnarine SI, Khawaja AM, Barnes PJ, Rogers DF. Nitric oxide inhibition of basal and neurogenic mucus secretion in ferret trachea in vitro. Br J Pharmacol 1996; 118: 998–1002.PubMedGoogle Scholar
  28. 28.
    Nagaki M, Shimura MN, Irokawa T, Sasaki T, Shirato K. Nitric oxide regulation of glycoconjugate secretion from feline and human airways in vitro. Respir Physiol 1995; 102: 89–95.PubMedCrossRefGoogle Scholar
  29. 29.
    Higenbottam T, Siddons T, Demoncheaux E. A therapeutic role for chronic inhaled nitric oxide? Lancet 2000; 356: 446–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Fratacci MD, Frostell CG, Chen TY, Wain JC Jr, Robinson DR, Zapol WM. Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep. Anesthesiology 1991; 75: 990–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Malmros C, Blomquist S, Dahm P, Martensson L, Thorne J. Nitric oxide inhalation decreases pulmonary platelet and neutrophil sequestration during extracorporeal circulation in the pig. Crit Care Med 1996; 24: 845–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Adrie C, Bloch KD, Moreno PR, et al. Inhaled nitric oxide increases coronary artery patency after thrombolysis. Circulation 1996; 94: 1919–26.PubMedGoogle Scholar
  33. 33.
    Russo G, Leopold JA, Loscalzo J. Vasoactive substances: nitric oxide and endothelial dysfunction in atherosclerosis. Vascul Pharmacol 2002; 38: 259–69.PubMedCrossRefGoogle Scholar
  34. 34.
    Jugdutt BI. Nitric oxide and cardioprotection during ischemia-reperfusion. Heart Fail Rev 2002; 7: 391–405.PubMedCrossRefGoogle Scholar
  35. 35.
    Leopold JA, Loscalzo J. New developments in nitrosovasodilator therapy. Vasc Med 1997; 2: 190–202.PubMedGoogle Scholar
  36. 36.
    Bloomfield GL, Holloway S, Ridings PC, et al. Pretreatment with inhaled nitric oxide inhibits neutrophil migration and oxidative activity resulting in attenuated sepsis-induced acute lung injury. Crit Care Med 1997; 25: 584–93.PubMedCrossRefGoogle Scholar
  37. 37.
    Chollet-Martin S, Gatecel C, Kermarrec N, Gougerot-Pocidalo MA, Payen DM. Alveolar neutrophil functions and cytokine levels in patients with the adult respiratory distress syndrome during nitric oxide inhalation. Am J Respir Crit Care Med 1996; 153: 985–90.PubMedGoogle Scholar
  38. 38.
    Rubbo H, Radi R, Anselmi D, et al. Nitric oxide reaction with lipid peroxyl radicals spares α-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/α-tocopherol than α-tocopherol/ascorbate. J Biol Chem 2000; 275: 10812–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Baldus S, Castro L, Eiserich JP, Freeman BA. Is NO news bad news in acute respiratory distress syndrome? Am J Respir Crit Care Med 2001; 163: 308–10.PubMedGoogle Scholar
  40. 40.
    Sittipunt C, Steinberg KP, Ruzinski JT, et al. Nitric oxide and nitrotyrosine in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2001; 163: 503–10.PubMedGoogle Scholar
  41. 41.
    Colasanti M, Persichini T. Nitric oxide: an inhibitor of NF-κB/Rel system in glial cells. Brain Res Bull 2000; 52: 155–61.PubMedCrossRefGoogle Scholar
  42. 42.
    Laroux FS, Pavlick KP, Hines IN, et al. Role of nitric oxide in inflammation. Acta Physiol Scand 2001; 173: 113–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Khan BV, Harrison DG, Olbrych MT, Alexander RW, Medford RM. Nitric oxide regulates vascular cell adhesion molecule 1 gene expression and redox-sensitive transcriptional events in human vascular endothelial cells. Proc Natl Acad Sci USA 1996; 93: 9114–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Kupatt C, Weber C, Wolf DA, Becker BF, Smith TW, Kelly RA. Nitric oxide attenuates reoxygenationinduced ICAM-1 expression in coronary microvascular endothelium: role of NFκB. J Mol Cell Cardiol 1997; 29: 2599–609.PubMedCrossRefGoogle Scholar
  45. 45.
    Shin WS, Hong YH, Peng HB, De Caterina R, Libby P, Liao JK. Nitric oxide attenuates vascular smooth muscle cell activation by interferon-γ. The role of constitutive NF-κB activity. J Biol Chem 1996; 271: 11317–24.PubMedCrossRefGoogle Scholar
  46. 46.
    Spiecker M, Peng HB, Liao JK. Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IκBα. J Biol Chem 1997; 272: 30969–74.PubMedCrossRefGoogle Scholar
  47. 47.
    Spiecker M, Darius H, Kaboth K, Hubner F, Liao JK. Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants. J Leukoc Biol 1998; 63: 732–9.PubMedGoogle Scholar
  48. 48.
    Perkins DJ, Kniss DA. Blockade of nitric oxide formation down-regulates cyclooxygenase-2 and decreases PGE2 biosynthesis in macrophages. J Leukoc Biol 1999; 65: 792–9.PubMedGoogle Scholar
  49. 49.
    Sheffler LA, Wink DA, Melillo G, Cox GW. Exogenous nitric oxide regulates IFN-γ plus lipopolysaccharideinduced nitric oxide synthase expression in mouse macrophages. J Immunol 1995; 155: 886–94.PubMedGoogle Scholar
  50. 50.
    Hubert BP, Blaise GA. Inhaled NO given perioperatively improves oxygenation and decreases pulmonary arterial resistance following cardiopulmonary bypass in a pig model. Anesthesiology 2001; 95: A-366 (abstract).Google Scholar
  51. 51.
    Hubert BP, Radomski M, Blaise GA. Does inhaled nitric oxide (inhNO) affect matrix-metalloproteinase (MMP) concentration in bronchoalveolar lavage fluid (BAL) after cardiopulmonary bypass (CPB)? Anesthesiology 2001; 95: A-440 (abstract).Google Scholar
  52. 52.
    Friese RS, Fullerton DA, McIntyre RC Jr, et al. NO prevents neutrophil-mediated pulmonary vasomotor dysfunction in acute lung injury. J Surg Res 1996; 63: 23–8.PubMedCrossRefGoogle Scholar
  53. 53.
    Neviere R, Guery B, Mordon S, et al. Inhaled NO reduces leukocyte-endothelial cell interactions and myocardial dysfunction in endotoxemic rats. Am J Physiol Heart Circ Physiol 2000; 278: H1783–90.PubMedGoogle Scholar
  54. 54.
    Miller OI, Tang SF, Keech A, Pigott NB, Beller E, Celermajer DS. Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study. Lancet 2000; 356: 1464–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Gross SS. Vascular biology. Targeted delivery of nitric oxide. Nature 2001; 409: 577–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Pawloski JR, Hess DT, Stamler JS. Export by red blood cells of nitric oxide bioactivity. Nature 2001; 409: 622–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Ramachandran N, Root P, Jiang XM, Hogg PJ, Mutus B. Mechanism of transfer of NO from extracellular Snitrosothiols into the cytosol by cell-surface protein disulfide isomerase. Proc Natl Acad Sci USA 2001; 98: 9539–44.PubMedCrossRefGoogle Scholar
  58. 58.
    Modin A, Bjorne H, Herulf M, Alving K, Weitzberg E, Lundberg JO. Nitrite-derived nitric oxide: a possible mediator of ‘acidic-metabolic’ vasodilation. Acta Physiol Scand 2001; 171: 9–16.PubMedCrossRefGoogle Scholar
  59. 59.
    Cannon RO III, Schechter AN, Panza JA, et al. Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide delivery. J Clin Invest 2001; 108: 279–87.PubMedGoogle Scholar
  60. 60.
    Troncy E, Francoeur M, Salazkin I, et al. Extra-pulmonary effects of inhaled nitric oxide in swine with and without phenylephrine. Br J Anaesth 1997; 79: 631–40.PubMedGoogle Scholar
  61. 61.
    Wraight WM, Young JD. Renal effects of inhaled nitric oxide in humans. Br J Anaesth 2001; 86: 267–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Weinberger B, Laskin DL, Heck DE, Laskin JD. The toxicology of inhaled nitric oxide. Toxicol Sci 2001; 59: 5–16.PubMedCrossRefGoogle Scholar
  63. 63.
    Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am J Physiol 1996; 271: C1424–37.PubMedGoogle Scholar
  64. 64.
    Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995; 268: L699–722.PubMedGoogle Scholar
  65. 65.
    van der Vliet A, Eiserich JP, Shigenaga MK, Cross CE. Reactive nitrogen species and tyrosine nitration in the respiratory tract. Epiphenomena or a pathobiologic mechanism of disease? Am J Respir Crit Care Med 1999; 160: 1–9.PubMedGoogle Scholar
  66. 66.
    Haddad IY, Zhu S, Crow J, Barefield E, Gadilhe T, Matalon S. Inhibition of alveolar type II cell ATP and surfactant synthesis by nitric oxide. Am J Physiol 1996; 270: L898–906.PubMedGoogle Scholar
  67. 67.
    Knepler JL Jr, Taher LN, Gupta MP, et al. Peroxynitrite causes endothelial cell monolayer barrier dysfunction. Am J Physiol Cell Physiol 2001; 281: C1064–75.PubMedGoogle Scholar
  68. 68.
    Szabo C, Cuzzocrea S, Zingarelli B, O’Connor M, Salzman AL. Endothelial dysfunction in a rat model of endotoxic shock. Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 1997; 100: 723–35.PubMedCrossRefGoogle Scholar
  69. 69.
    Zouki C, Zhang SL, Chan JS, Filep JG. Peroxynitrite induces integrin-dependent adhesion of human neutrophils to endothelial cells via activation of the Raf-1/MEK/Erk pathway. FASEB J 2001; 15: 25–7.PubMedGoogle Scholar
  70. 70.
    Soriano FG, Pacher P, Mabley J, Liaudet L, Szabo C. Rapid reversal of the diabetic endothelial dysfunction by pharmacological inhibition of poly(ADP-ribose) polymerase. Circ Res 2001; 89: 684–91.PubMedCrossRefGoogle Scholar
  71. 71.
    Szabo C, Billiar TR. Novel roles of nitric oxide in hemorrhagic shock. Shock 1999; 12: 1–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Black SM, Heidersbach RS, McMullan DM, Bekker JM, Johengen MJ, Fineman JR. Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension. Am J Physiol 1999; 277: H1849–56.PubMedGoogle Scholar
  73. 73.
    Dotsch J, Demirakca S, Zepf K, Hanze J, Parida S, Rascher W. Recovery from withdrawal of inhaled nitric oxide and kinetics of nitric oxide-induced inhibition of nitric oxide synthase activity in vitro. Intensive Care Med 2000; 26: 330–5.PubMedCrossRefGoogle Scholar
  74. 74.
    McMullan DM, Bekker JM, Johengen MJ, et al. Inhaled nitric oxide-induced rebound pulmonary hypertension: role for endothelin-1. Am J Physiol Heart Circ Physiol 2001; 280: H777–85.PubMedGoogle Scholar
  75. 75.
    Wedgwood S, McMullan DM, Bekker JM, Fineman JR, Black SM. Role for endothelin-1-induced superoxide and peroxynitrite production in rebound pulmonary hypertension associated with inhaled nitric oxide therapy. Circ Res 2001; 89: 357–64.PubMedCrossRefGoogle Scholar
  76. 76.
    Sheehy AM, Burson MA, Black SM. Nitric oxide exposure inhibits endothelial NOS activity but not gene expression: a role for superoxide. Am J Physiol 1998; 274: L833–41.PubMedGoogle Scholar
  77. 77.
    Troncy E, Collet JP, Shapiro S, et al. Inhaled nitric oxide in acute respiratory distress syndrome. A pilot randomized controlled study. Am J Respir Crit Care Med 1998; 157: 1483–8.PubMedGoogle Scholar
  78. 78.
    Jacobs BR, Brilli RJ, Ballard ET, Passerini DJ, Smith DJ. Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury. Am J Respir Crit Care Med 1998; 158: 1536–42.PubMedGoogle Scholar
  79. 79.
    Brilli RJ, Krafte-Jacobs B, Smith DJ, Passerini D, Moore L, Ballard ET. Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension. Crit Care Med 1998; 26: 1390–6.PubMedCrossRefGoogle Scholar
  80. 80.
    Adrie C, Ichinose F, Holzmann A, Keefer L, Hurford WE, Zapol WM. Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension. J Appl Physiol 1998; 84: 435–41.PubMedGoogle Scholar
  81. 81.
    Meadow W, Rudinsky B, Bell A, Hipps R. Effects of nebulized nitroprusside on pulmonary and systemic hemodynamics during pulmonary hypertension in piglets. Pediatr Res 1998; 44: 181–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Schutte H, Grimminger F, Otterbein J, et al. Efficiency of aerosolized nitric oxide donor drugs to achieve sustained pulmonary vasodilation. J Pharmacol Exp Ther 1997; 282: 985–94.PubMedGoogle Scholar
  83. 83.
    Gong F, Shiraishi H, Kikuchi Y, et al. Inhalation of nebulized nitroglycerin in dogs with experimental pulmonary hypertension induced by U46619. Pediatr Int 2000; 42: 255–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Palhares DB, Figueiredo CS, Moura AJ. Endotracheal inhalatory sodium nitroprusside in severely hypoxic newborns. J Perinat Med 1998; 26: 219–24.PubMedCrossRefGoogle Scholar
  85. 85.
    Ichinose F, Adrie C, Hurford WE, Bloch KD, Zapol WM. Selective pulmonary vasodilation induced by aerosolized zaprinast. Anesthesiology 1998; 88: 410–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Ichinose F, Erana-Garcia J, Hromi J, et al. Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension. Crit Care Med 2001; 29: 1000–5.PubMedCrossRefGoogle Scholar
  87. 87.
    Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension. Comparison with inhaled nitric oxide. Circulation 2002; 105: 2398–403.PubMedCrossRefGoogle Scholar
  88. 88.
    Haraldsson A, Kieler-Jensen N, Ricksten SE. The additive pulmonary vasodilatory effects of inhaled prostacyclin and inhaled milrinone in postcardiac surgical patients with pulmonary hypertension. Anesth Analg 2001; 93: 1439–45.CrossRefGoogle Scholar
  89. 89.
    Haraldsson A, Kieler-Jensen N, Nathorst-Westfelt U, Bergh CH, Ricksten SE. Comparison of inhaled nitric oxide and inhaled aerosolized prostacyclin in the evaluation of heart transplant candidates with elevated pulmonary vascular resistance. Chest 1998; 114: 780–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Hoeper MM, Olschewski H, Ghofrani HA, et al. A comparison of the acute hemodynamic effects of inhaled nitric oxide and aerosolized iloprost in primary pulmonary hypertension. German PPH study group. J Am Coll Cardiol 2000; 35: 176–82.PubMedCrossRefGoogle Scholar
  91. 91.
    Hill LL, Pearl RG. Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension. J Appl Physiol 1999; 86: 1160–4.PubMedGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2003

Authors and Affiliations

  • Tianlong Wang
    • 1
  • Driss El Kebir
    • 1
  • Gilbert Blaise
    • 1
  1. 1.Department of Anesthesiologyl’Hôpital Notre-Dame du CHUM, Université de MontréalMontréalCanada
  2. 2.Laboratoire d’AnesthésiePavillon Deschamps, Local FS-1136, Hôpital Notre-Dame du CHUMMontréalCanada

Personalised recommendations