MUCOLYTIC TREATMENT WITH N-ACETYLCYSTEINE L-LYSINATE METERED-DOSE INHALER IN DOGS - AIRWAY EPITHELIAL FUNCTION CHANGES

N-acetylcysteine L-lysinate Nacystelyn(R) (L-NAC) is a newly synthesiz ed mucolytic agent, of which the action in vivo has not been well defi ned. In six healthy mongrel dogs, the theological properties of mucus, its mucociliary and cough clearability, and the transepithelial poten tial difference (PD) of the tracheobronchial epithelium were evaluated after placebo and L-NAC metered dose inhaler (MDI) aerosols. The prin cipal index of mucus rigidity, log G, decreased at all airway sites w ith L-NAC administration, ie. the mucus became less rigid and more def ormable (the overall change in G was 0.29 log units, i.e. ca. twofold decrease). The viscoelasticity-derived mucus transportability paramet ers, mucociliary (MCI) and cough (CCI) clearability indices, increased with L-NAC MDI, particularly CCI, which pre diets the effect of mucus theology on cough clearability. PD increased significantly with L-NAC administration at all measurement sites, which appears to be a novel effect for a direct acting mucolytic agent. Tracheal mucus linear velo city (TMV) increased after L-NAC compared with placebo, as did the nor malized frog palate transport rate (NFPTR). The increase in NFPTR was greater than that predicted from the mucus rheological properties alon e, suggesting that L-NAC still resident in the collected mucus stimula ted the frog palate cilia. The index of mucus flux, the collection rat e in mg min(-1), was higher with L-NAC compared with placebo. From our results, we conclude that L-NAC shows potential benefit in terms of i mproving mucus theological properties and clearability. It may act, in part, by stimulating the fresh secretion of mucus of lower viscoelast icity. The stimulation of mucociliary clearance could be related to io n flux changes, as indicated by the increase in PD.