Comparative effects of salmeterol, albuterol, and ipratropium on normal and impaired mucociliary function in sheep.
OBJECTIVE
We measured tracheal mucus velocity (TMV), a marker of mucociliary clearance (MCC), in sheep before and for 12 h after treatment with salmeterol, albuterol, ipratropium, or vehicle to determine the effects on normal MCC. We also determined if these agents could reverse the depression in TMV caused by inhaled human neutrophil elastase (HNE), a model of abnormal MCC.


METHODS
Study 1: TMV was measured initially and then for 6 h after metered-dose inhaler treatment with salmeterol (42 microg), albuterol (180 microg), ipratropium bromide (36 microg), or vehicle. After 6 h, the sheep in the albuterol and ipratropium treatment arms were administered a second dose of drug, whereas the salmeterol and vehicle treatment arms received vehicle. TMV was measured for another 6 h. Study 2: Six sheep inhaled HNE aerosol, which significantly reduced TMV by 2 h. At this point, the sheep were treated with either salmeterol, albuterol, ipratropium, or vehicle, and the effects on TMV were measured for another 6 h. This experiment was repeated in four sheep using only salmeterol and albuterol, but the posttreatment measurements were extended to 12 h.


RESULTS
Study 1: Only salmeterol and albuterol increased TMV (p < 0.05) during the initial 6-h period. From 6 to 12 h only, the salmeterol-treated sheep had TMV that remained at or above the initial TMV for the entire time, although both albuterol and ipratropium showed enhancement of TMV compared to vehicle. Study 2: Salmeterol and albuterol reversed the HNE-induced depression in TMV to a similar degree over the 6-h time course. However, the protection afforded by salmeterol was more prolonged than that seen with albuterol if the posttreatment interval was extended to 12 h. Ipratropium and vehicle had no effect.


CONCLUSIONS
We conclude that salmeterol and albuterol can stimulate normal MCC and reverse HNE-induced mucociliary dysfunction and that salmeterol has a longer duration of action in these models of normal and abnormal MCC.
Sabater
Juan R
JR
Division of Pulmonary and Critical Care Medicine, Miller School of Medicine, University of Miami at Mount Sinai Medical Center, FL 33140, USA.
Lee
Troy A
TA
Abraham
William M
WM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D009241:Ipratropium / Q000494:pharmacology*; D009079:Mucociliary Clearance / Q000187:drug effects*; D000068299:Salmeterol Xinafoate; D012756:Sheep; D014132:Trachea / Q000502:physiology
D000318:Adrenergic beta-Agonists; D018680:Cholinergic Antagonists; D000068299:Salmeterol Xinafoate; D009241:Ipratropium; D000420:Albuterol