Effect of N-acetylcysteine on gas exchange after methacholine challenge and isoprenaline inhalation in the dog

Abstract

N-acetylcysteine (NAC) has antioxidant and possibly mucolytic properties. To determine whether NAC could be of benefit in acute bronchoconstriction induced by methacholine, 12 of 24 anaesthetized dogs (group 1) received NAC i.v. (loading dose 150 mg·kg-1, then 20 mg·kg-1·hr-1). The other 12 (group 2) received diluent. Nebulized methacholine (1 %) was then inhaled until arterial oxygen tension (PaO2) fell to a mean of 5.5 kPa, after which isoprenaline 0.5 % inhaled in six dogs of each group to reverse bronchoconstriction. Over the next 3 h we measured total lung resistance, functional residual capacity (FRC), haemodynamic variables, and pulmonary gas exchange for respiratory and inert gases. After metacholine challenge, lung resistance increased and then fell similarly for both groups, but PaO2 was higher in the NAC group (by 0.6-1.9 kPa) throughout the observation period. The ventilation-perfusion distribution measured by inert gas elimination also showed less abnormality in the NAC treated dogs over this time. Mucus was visible during post-mortem in the large airways in about half of the dogs in both groups, with no significant differences between them. These results show that NAC produces a measurable improvement in gas exchange following methacholine challenge (both with and without subsequent isoprenaline therapy) by mechanisms that remain to be determined.