The Effect of Stimulatory Compounds on Baseline and Impaired Mucociliary Clearance in the Guinea Pig

Abstract

Mucociliary clearance (MCC) is an important mechanism for clearing the lung of foreign matter and is impaired in diseases such as COPD. Smoking reduces MCC in humans and may contribute to the disease, whereas agents such as β2-adrenergic agonists, hypertonic saline and mannitol are known to increase MCC rate. We have developed a model which can be used to identify compounds with potential to increase or rectify defective MCC. Methods Guinea pigs were exposed to air or tobacco smoke (TS) for 4 days and 24hrs after the last exposure the trachea was exposed and fluorescent beads applied via a small cut near the carina. After a set time, the distance traveled by the beads was visualised and measured. Isotonic saline, hypertonic saline (7%), mannitol (16%) or Formoterol (1.7µg/kg) were dosed i.n. 1hr prior to bead administration. All data are given as mean±SD. Results Administration of mannitol increased (+62%, p<0.001) MCC rate compared to air-exposed controls (5.44±0.93 vs 3.36±0.65mm/min). Hypertonic saline had no effect (3.91±0.96 vs 3.36±0.65mm/min). Formoterol, at a known bronchodilator dose, also reproducibly increased (+65%) MCC rate (5.56±1.69 vs 3.34±1.17mm/min). Exposure to TS caused a marked decrease (-36%) in MCC rate (3.88±1.03 vs 2.49±0.72mm/min, p<0.001). The TS-induced reduction in MCC rate was reproducible over 5 separate studies. Formoterol significantly increased MCC rate (+60%) in the TS-exposed animals (3.71±0.54 vs 2.49±0.72mm/min, p<0.05) to within air exposed, vehicle control group levels. This model demonstrates that MCC rate can be reproducibly measured in the guinea pig trachea. The baseline rate can be enhanced by Formoterol and mannitol, impaired by TS-exposure and subsequently restored to baseline rate by Formoterol. Funded by Argenta