Regional Lung Blood Flow and Inhalation of Nitric Oxide
It did not take long after it was discovered that nitric oxide is produced in the vascular wall of endothelial cells and that it has a powerful vasodilatory effect until efforts were made to modify the pulmonary vascular tone by either inhaling NO or blocking its endogenous production by means of an NO synthase inhibitor. Thus, lambs were exposed either to hypoxic gas or to a thromboxane analogue in order to constrict the vessels and subsequent inhalation of 5–80 parts per million (ppm) of NO was shown to relax the pulmonary vessels in a dose-dependent manner [1, 2]. In similar experiments, healthy humans exposed to hypoxic gas (12% O2) did also respond with pulmonary vasorelaxation back to baseline on inhalation of NO in doses of 5–40 ppm . The inhalation of NO, however, did not affect systemic arterial pressure, neither in the lambs nor in the human volunteers. This can be explained by the avid binding of NO to haemoglobin (met-haemoglobin) which does not exert an NO vasoactive effect. In similar experiments in patients with acute respiratory failure, inhalation of NO could also lower pulmonary artery pressure in the presence of pulmonary hypertension . Moreover, in these patients an improvement in arterial oxygenation was also seen which may be due to a redistribution of lung blood flow to ventilated regions from non-ventilated shunt areas. This is because inhaled NO will only exert its dilatory effect in those lung regions reached by NO. This is different from the effect of a systemically administered vasodilator, for example, sodium nitroprusside, nitroglycerine or prostacycline. These will dilate vessels both in ventilated and non-ventilated lung regions, usually with a more powerful relaxant effect in the non-ventilated shunt regions because their preceding hypoxic vasoconstriction. Moreover, a systemic hypotension may also develop. Thus, for the first time it seemed as if a drug exerted its effect only on pulmonary circulation and ventilated lung regions. Subsequent studies on nebulisation of the airways using prostacycline has also been shown to exert its effect solely where it has been deposited in the lung; similar to inhaled NO . In neonates with the persistent pulmonary hypertension a dramatic fall in the pulmonary artery pressure and increasing PaO2 was observed NO inhalation , raising high expectations on the usefulness of NO as a life saving drug in adult and in neonatal ARDS.
KeywordsNitric Oxide Acute Respiratory Distress Syndrome Pulmonary Artery Pressure Congenital Diaphragmatic Hernia Hypoxic Pulmonary Vasoconstriction
Unable to display preview. Download preview PDF.
- 5.Walmrath D, Schneider T, Schermuly R et al (1996) Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome. Am J Respir Crit Care Med Mar 153 (3): 991–996Google Scholar
- 18.Wilson WC, Kapelanski DP, Benumof JL et al (1997) Inhaled nitric oxide (40 ppm) during one-lung ventilation, in the lateral decubitus position, does not decrease pulmonary vascular resistance or improve oxygenation in normal patients. J Cardiothorac Vasc Anesth 11 (2): 172–176PubMedCrossRefGoogle Scholar
- 19.Hartigan P, Formanek V, Sheman S et al (1996) Inhaled NO fails to improve gas exchange during one-lung ventilation (abstr). Anesthesiology 85: A1165Google Scholar
- 20.Booth J, Powrosnyk A, Oduru A et al (1995) Effect of nitric oxide on arterial oxygenation and pulmonary shunt during one-lung ventilation (abstr). Anesthesiology 83:Al201Google Scholar
- 21.Hambraeus Jonzon K, Bindslev L, Frostell C, Hedenstierna G (1998) Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide. Eur Respir J 11: 565–570Google Scholar