Nitric Oxide: Lessons Learned and Areas of Success

  • W. M. Zapol
  • R. Jenney
Conference paper


Pulmonary hypertension with severe hypoxemia complicates the care of patients with diseases such as acute respiratory distress syndrome (ARDS), pulmonary embolism, chronic respiratory failure, chronic pulmonary hypertension, and after cardiopulmonary bypass. Pulmonary hypertension is also common in newborn patients with prematurity, meconium aspiration, pneumonia, sepsis, and congenital diaphragmatic hernias and in infants and children with many forms of congenital heart disease. Currently available intravenous vasodilator therapies often cause untoward effects when used to reduce pulmonary hypertension. For example, systemic vasodilatation and hypotension occur with all vasodilators infused at dosages sufficient to decrease pulmonary hypertension. In addition, intravenous infusions of systemic vasodilators often increase the venous admixture due to right to left shunting of venous blood. It is extremely desirable to identify a vasodilator that selectively relaxes constricted pulmonary arteries, and does not cause systemic dilatation or increased pulmonary venous admixture.


Nitric Oxide Nitric Oxide Pulmonary Hypertension Acute Respiratory Distress Syndrome Pulmonary Artery Pressure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE (1987) Endothelium-derived relaxing factor produced and released from artery and vein is NO. Proc Natl Acad Sci USA 84: 9265–9269PubMedCrossRefGoogle Scholar
  2. 2.
    Ignarro LJ (1990) Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol 41: 485–490CrossRefGoogle Scholar
  3. 3.
    Gerlach H, Rossaint R, Pappert D (1994) Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx. Lancet 343: 518–519PubMedCrossRefGoogle Scholar
  4. 4.
    Dinh Xuan AT, Higenbottam TW, Clelland C et al (1991) Impairment of endothelium-dependent pulmonary artery relaxation in chronic obstructive lung disease. N Engl J Med 324: 1539–1547PubMedCrossRefGoogle Scholar
  5. 5.
    Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT et al (1991) Inhaled nitric oxide as a cause of selective pulmonary vasodilation in pulmonary hypertension. Lancet 338: 1173–1174PubMedCrossRefGoogle Scholar
  6. 6.
    Frostell C, Fratacci M-D, Wain JC et al (1991) Inhaled nitric oxide: A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction. Circulation 83: 2038–2047PubMedGoogle Scholar
  7. 7.
    Roberts JD Jr, Chen T-Y, Kawai N et al (1993) Inhaled nitric oxide reverses pulmonary vasoconstriction in the hypoxic and acidotic newborn lamb. Circulation Research 72: 246–254PubMedGoogle Scholar
  8. 8.
    Rossaint R, Falke KJ, Lopez F et al (1993) Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 328: 399–405PubMedCrossRefGoogle Scholar
  9. 9.
    Gerlach H, Pappert D, Lewandowski K et al (1993) Long term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome. Intensive Care Medicine 19: 443–449PubMedCrossRefGoogle Scholar
  10. 10.
    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: A350Google Scholar
  11. 11.
    Dellinger RP, Zimmerman JL, Taylor RW et al (1998) Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: Results of a randomized phase II trial. Crit Care Med 26: 15–23PubMedCrossRefGoogle Scholar
  12. 12.
    Wysocki M, Delclaux C, Roupie E et al (1994) Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome. Inten Care Med 20: 254–259CrossRefGoogle Scholar
  13. 13.
    Roberts JD, Polaner DM, Lang P, Zapol WM (1992) Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 818–819PubMedCrossRefGoogle Scholar
  14. 14.
    Kinsella JP, Shaffer E, Neish SR, Abman SH (1992) Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 8819–8820CrossRefGoogle Scholar
  15. 15.
    Roberts JD Jr, Lang P, Bigatello L et al (1993) Inhaled nitric oxide in congenital heart disease. Circulation 87: 447–453PubMedGoogle Scholar
  16. 16.
    Roberts JD Jr, Fineman JR, Morin FC et al (1997) Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. N Engl J Med 336(9): 605–610PubMedCrossRefGoogle Scholar
  17. 17.
    The Neonatal Inhaled Nitric Oxide Study Group (1997) Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 336(9): 597–604CrossRefGoogle Scholar
  18. 18.
    Garg UC, Hassid A (1989) Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. Journal of Clinical Investigation 83: 1774–1777PubMedCrossRefGoogle Scholar
  19. 19.
    Roberts JD, Roberts CT, Jones RC, Zapol WM (1995) Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy, and growth retardation in the hypoxic newborn rat. Circ Res 76: 215–222PubMedGoogle Scholar
  20. 20.
    Kouyoumdjian C, Adnot S, Levame M et al (1994) Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats. Journal of Clinical Investigation 94: 578–584PubMedCrossRefGoogle Scholar
  21. 21.
    Clark RH, Kueser TJ, Walker MW et al for the Clinical Inhaled Nitric Oxide Research Group (2000) Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med 342: 469–474PubMedCrossRefGoogle Scholar
  22. 22.
    Steudel W, Hurford WE, Zapol WM (1999) Inhaled Nitric Oxide: Basic Biology and Clinical Applications. Anesthesiology 91: 1090–1121PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia, Milano 2001

Authors and Affiliations

  • W. M. Zapol
  • R. Jenney

There are no affiliations available

Personalised recommendations