Inhalation of nitric oxide

Lundin S, Mang H, Smithies M, Stenqvist O, Frostell C. Inhalation of nitric oxide in acute lung injury results of a European multicentre study. The European Study Group of Inhaled Nitric Oxide. Intensive Care Med 1999 25(9) 911-19. 

Hitman, M., Frostell, C.G., Hedenstrom and Hendenstiema, G. (1993). Inhalation of nitric oxide modulates adult bronchial tone. Am. Rev. Respir. Dis. 148, 1474—1478. 

Blomqvist, H., Wickerts, C.-J., Andreen, M., Ullberg, U., Ortqvist, A., and Frostell, C. (1993). Enhanced pneumonia resolution by inhalation of nitric oxide Acta Anaesthesiol. Scand. 37, 110-114. 

Putensen, C., Rasanen, J., and Lopez, F. (1994). VA/Q distributions improve during inhalation of nitric oxide in pigs with methacholine-induced bronchoconstriction. Anesthesiology 81(Supp. 3A), A1441 (abstr.). 

Nitric oxide also produces vasodilation in vascular smooth muscle. As indicated earlier, hypertension may be perpetuated by a defect in the production of nitric oxide by the vascular endothelium. In follows that providing nitric oxide directly or administering precursors for nitric oxide production may help reduce vascular resistance and decrease arterial pressure in specific hypertensive syndromes.6 To date, inhaled nitric oxide has been used to treat acute pulmonary hypertension associated with respiratory distress syndrome in new-... 

The inhaling of small quantities of nitric oxide can help premature babies (or babies with holes in the heart) to breathe and prevent serious lung disorders. 

Nitric oxide, a precursor of nitrogen dioxide, occurs naturally in the human body, where it acts as endothelial derived relaxing factor (EDRF), a neurotransmitter, and in unidentified ways in the nose, sinuses, and lower airways. Up to 15 ppm can be found normally in the nose and sinuses (DuBois et al. 1998). The substrate is 1-arginine, and the enzymes consist of different forms of nitric oxide synthase, which turn arginine into citrulline. Inhaled nitric oxide gas is used at concentrations of up to 50 ppm to decrease pulmonary arterial pressure. Nitric oxide reacts in tissues to form nitrites and nitrates. 

Sir Humphry Davy in 1800 showed the toxicity of NO during experiments on the effectiveness of inhaled gases for relief of asthma in his work on nitrous oxide. The paradoxical actions of nitric oxide may come down to the particular concentration and duration of production and also on the availability of molecular targets and reactions with other available substrates [101]. 

Saleh D, Ernst P, Lim S, Barnes PJ, Giad A. Increased formation of the potent oxidant peroxynitrite in the airways of asthmatic patients is associated with induction of nitric oxide synthase effect of inhaled glucocorticoid. FASEB J 12 (1998) 929-937. 

There have been several case reports that high doses of nitric oxide (40-80 ppm) reduce pulmonary vascular resistance and increase pulmonary capillary wedge pressure in some patients with left ventricular dysfunction. The acute increase in left ventricular filling pressure that ensues can cause or exacerbate pulmonary edema. The author concluded that in patients with severe left ventricular dysfunction (pulmonary capillary wedge pressure over 25 mmHg) it would be prudent to avoid the use of inhaled nitric oxide. 

One of the biochemical adverse effects of nitric oxide is inactivation of vitamin B12, with subsequent potentiation of folate deficiency (19). This effect is mediated by irreversible oxidation of the cobalt residue in vitamin B12 to its Co++ and Co forms. This leads to a reduction in methionine synthetase activity, with downstream effects on DNA synthesis. Previous studies have identified five patients with unsuspected vitamin B12 deficiency who developed subacute combined degeneration of the spinal cord following inhalation anesthesia with nitrous oxide... 

In a retrospective case-control study, 12 children with severe pulmonary hypertension were treated with inhaled nitric oxide followed by prostacyclin 10 ng/kg/minute for 24 hours before gradual withdrawal of nitric oxide the 12 matched controls did not receive prostacyclin (27). Only one of the patients developed rebound hypertension, indicated by arterial desaturation (a 5% or greater fall in Sa02 within 4 hours of withdrawal), while eight of 12 controls developed the rebound effect. 

Ashutosh K, Phadke K, Jackson JF, Steele D. Use of nitric oxide inhalation in chronic obstructive pulmonary disease. Thorax 2000 55(2) 109-13. 

Combes X, Mazmanian M, Gourlain H, Herve P. Effect of 48 hours of nitric oxide inhalation on pulmonary vasoreactivity in rats. Am J Respir Crit Care Med 1997 156(2 Pt l) 473-7. 

A small-scale but important use of ammonium nitrate is for the preparation of inhalation grade nitrous oxide for use as an anaesthetic. This is achieved by heating pure ammonium nitrate to about 200-250°C (Eq. 11.53), which gives nitrous oxide virtually free of nitric oxide or... 

This work was supported in part by grant 9073 from the Swedish Medical Research Council and by grant HL-42397 from the U.S. National Heart, Lung and Blood Institute. C.G.F. and W.M.Z. are part-time consultants to industry on the development of therapeutic inhaled NO. The Massachusetts General Hospital has obtained a patent on the respiratory uses of nitric oxide. 

Bigatello, L. M., Hurford, W. E., Kacmarek, R. M., Roberts, J. D., and Zapol, W. M. (1994). Prolonged inhalation of low levels of nitric oxide in patients with severe ARDS Effects on pulmonary hemodynamics and oxygenation. Anesthesiology 80, 761-770. 

Gerlach, H., Rossaint, R., Pappert, D., and Falke, K. J. (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, 499-502. 

Lundin, S., Westfelt, U., Stenqvist, O., Blomqvist, H., Linkh, A., Berggren, L., and Frostell, C. G. (1994). Dose-response of nitric oxide inhalation in early acute lung injury. Br. J. Anaesth. 72(Suppl), A106 (abstr.). 

Young, J. D., Dyar, O., Xiong, L., and Howell, S. (1994). Methaemoglobin production in normal adults inhaling low concentrations of nitric oxide. Intens. Care Med. 20,581-584. 

FIGURE 10 Effects of nitric oxide (NO) inhalation on pulmonary artery (PA) pressure (PAp) and trapulmonary shunt fraction (Qs/Qt) in one patient during the first 36 hr after lung transplantation. PAp and Qs/Qt improved with NO and deteriorated during reductions in the NO dose. [Reproduced with permission from Adatia et al. (77).]... 

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