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Effects of inhaled nitric oxide on methacholine-induced bronchoconstriction: a concentration response study in
M Högman1, S Z Wei, C Frostell
1Dept of Clinical Physiology, University Hospital, Uppsala, Sweden.
Abstract:
Inhaled nitric oxide (NO), at a concentration of 80 ppm, counters the increase in respiratory resistance (Rrs) induced by methacholine, but fails to prevent a reduction in lung compliance (Crs) in a rabbit model. This study reports the effects of 3, 30 and 300 ppm of inhaled NO. New Zealand White rabbits were intubated and mechanically ventilated with 30% oxygen during neurolept anaesthesia. Methacholine (3 mg.ml-1) was nebulized, with or without NO inhalation. Inhalation of 3 and 30 ppm NO had no effect on the induced bronchoconstriction, whereas 300 ppm fully blocked the increase in Rrs. The decrease in Crs due to methacholine was not countered by 3, 30 or 300 ppm NO. On the contrary, inhalation of 300 ppm NO in itself decreased Crs from 5.0 +/- 0.1 to 4.3 +/- 0.1 ml.cmH2O-1. Also, mean arterial pressure (60 +/- 7 to 54 +/- 5 mmHg), alveolar-arterial oxygen tension gradient (0.8 +/- 0.8 to 2.3 +/- 1.8 kPa) and methaemoglobin (0.5 +/- 0.2 to 1.5 +/- 0.5%) changed significantly on inhalation of NO 300 ppm prior to methacholine challenge. We conclude that 3 and 30 ppm NO inhalation does not alter methacholine-induced bronchoconstriction. Inhalation of 300 ppm NO blocks an increase in resistance but fails to counter the reduction in compliance due to methacholine. This suggests that the bronchodilating effects of NO in rabbits in vitro are confined to the large airways.
Insights
Inhaled nitric oxide (NO) at 300 ppm blocked methacholine-induced respiratory resistance increases in rabbits but did not affect lung compliance. Higher NO concentrations also reduced compliance and altered physiological parameters.
Area of Science:
- Pulmonary Physiology
- Pharmacology
Background:
- Inhaled nitric oxide (NO) is known to affect respiratory mechanics.
- Previous studies indicated NO's efficacy at 80 ppm in mitigating methacholine-induced respiratory resistance (Rrs).
- However, its effect on lung compliance (Crs) and varying concentrations remained unclear.
Purpose of the Study:
- To investigate the dose-dependent effects of inhaled nitric oxide (NO) on methacholine-induced bronchoconstriction and changes in lung mechanics in rabbits.
- To determine the impact of different NO concentrations on respiratory resistance (Rrs) and lung compliance (Crs).
Main Methods:
- New Zealand White rabbits were mechanically ventilated under anesthesia.
- Methacholine challenge was administered with or without varying concentrations of inhaled NO (3, 30, and 300 ppm).
- Respiratory resistance (Rrs), lung compliance (Crs), mean arterial pressure, alveolar-arterial oxygen tension gradient, and methaemoglobin levels were measured.
Main Results:
- Inhaled NO at 3 and 30 ppm did not affect methacholine-induced bronchoconstriction.
- 300 ppm of inhaled NO fully prevented the increase in respiratory resistance (Rrs) but did not counteract the reduction in lung compliance (Crs).
- 300 ppm NO alone decreased Crs and significantly altered mean arterial pressure, alveolar-arterial oxygen tension gradient, and methaemoglobin levels.
Conclusions:
- Low concentrations (3 and 30 ppm) of inhaled NO are ineffective against methacholine-induced bronchoconstriction in rabbits.
- A high concentration (300 ppm) of inhaled NO demonstrates bronchodilating effects on large airways but exacerbates decreases in lung compliance.
- These findings suggest that the bronchodilating effects of NO in rabbits are primarily limited to larger airways and high doses can induce adverse physiological changes.