The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138±0.004 (mean±SE) to 0.125±0.002 cmH2O/ml s (P < 0.05). When an intravenous infusion of methacholine (3.5-12 ,ug/kg-min) was used to increase RL from 0.143±0.008 to 0.474±0.041 cmH2O/ml. s (P < 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0±2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (< 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453±0.022 to 0.287±0.022 cmH2O/ml s, which lasted for over 15 min in guinea pigs bronchoconstricted with methacholine. Our results indicate that low levels ofinhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs. (J. Clin. Invest. 1992. 90:421428.)

During a study on the modulatory effect of inhaled nitric oxide (NO) on the airway, we observed an increased bleeding tendency. Therefore, we studied bleeding time and blood rheology in rabbits during inhalation of 3, 30 and 300 parts per million (ppm) NO. The rabbits were intubated during neurolept anaesthesia and were ventilated mechanically. The bleeding time was significantly increased after 15 min of inhalation of 30 ppm NO, from 51 +/- 5 to 72 +/- 7 s (mean +/- SEM, P < 0.001, n = 7). However, there were no changes in haematocrit, whole blood or plasma viscosity, erythrocyte aggregation tendency, or erythrocyte deformability. Inhalation of 3 ppm NO increased bleeding time from 46 +/- 11 to 59 +/- 8 s (n.s., n = 4) and 300 ppm NO from 48 +/- 12 to 78 +/- 17 s (P < 0.05, n = 4). In another group of rabbits mean arterial pressure (MAP) was monitored using NO inhalation. A non-significant decrease was seen with 3 ppm and 30 ppm NO, from 63 +/- 2 to 59 +/- 3 mmHg (n = 6) and from 65 +/- 2 to 61 +/- 1 mmHg (n = 6) respectively. Inhalation with 300 ppm NO decreased MAP from 62 +/- 3 to 55 +/- 2 mmHg (P < 0.05, n = 6). We conclude from these data that inhalation of NO, 30 ppm or more exerts systemic effects.

This first placebo-controlled study indicates that inhaled NO does not influence either bleeding time, platelet activity or skin perfusion. Thus, it is unlikely that treatment of critically ill patients with inhaled NO will aggravate haemostatic disturbances, which has previously been feared, by influencing platelet function.

The effect on gas exchange of increasing concentrations of nitric oxide (0-60 parts per million) added to the inspired gases of nine ventilator-dependent infants (median postnatal age = 4 weeks; range 2-16 weeks) with chronic lung disease and pathological oxygenation index values was studied by means of arterial or transcutaneous PO2/PCO2. A significant improvement of oxygenation, indicated by a reduction of oxygenation index, was found (p < 0.014). The optimal nitric oxide concentration and the individual response varied between patients. PO2 returned to baseline values after the discontinuation of nitric oxide in all patients except one. No effect on PCO2 could be identified. Methaemoglobin values only increased marginally during the nitrous oxide exposition (pre-nitric oxide: 0.56% +/- 0.27; post-nitric oxide: 0.78 +/- 0.08; p = ns). Systemic blood pressure and heart rate were unaffected in all patients. Before inhaled nitric oxide can be considered for prolonged use in this patient category further studies regarding long-term efficacy and safety are needed.

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