Influence of Inhaled Atropine on Lung Mucociliary Function in Humans

Abstract

The influence of aerosolized atropine sulfate on lung airway mucus clearance was investigated in healthy human subjects who were nonsmokers. Mucus transport was measured with radiolabeled insoluble particles inhaled by mouth and deposited onto mucosal surfaces; subsequent retention of radiolabel was quantitated over a 4- to 5-h period by a noninvasive, posteriorly aligned, gamma camera. Placebo and atropine clearance tests were matched in a given subject for initial and for final (24-h postinhalation) deposition pattern of labeled aerosol at the onset and conclusion, respectively, of tracheobronchial particle clearance. In seven subjects mucociliary function was delayed after inhalation of 0.025 mg/kg body weight atropine sulfate as compared with placebo (0.9% NaCl). On the basis of the area under the activity versus time curves, retention times during atropine exceeded placebo times by more than 30% (p less than 0.01). At 90 min postatropine inhalation, the Vmax50 exceeded baseline values by 21% (p less than 0.01). Urine retention was present in one subject and xerostomia was present in all subjects after atropine. These data suggest that a single dose of atropine sulfate delivered topically to the airway surfaces delays the continuous flow of airway mucus in healthy subjects and that basal autonomic tone is an inherent factor for optimal secretion and/or removal of tracheobronchial secretions.

<i>In Vitro</i> Evaluation of Nasal Mucociliary Clearance Using Excised Rat Nasal Septum

“…Effect of Various Drugs on Mucociliary Clearance For the validation of the system, the effects of drugs known to change MC were evaluated. Benzalkonium chloride (BZC), a preservative often used for nasal dosage forms, 21,22) propranolol (PPL) and atenolol (ATL), β-adrenergic antagonists, 23,24) salbutamol (SBM) and terbutaline (TBL), β-adrenergic agonists, [25][26][27] acetylcholine (ACH), a cholinergic agonist, 14,27,28) and atropine (ATRP), a cholinergic antagonist, 29) were employed to examine their effects on MC. Each drug was dissolved in HBSS at two different concentrations.…”

Effects of morphine on human nasal cilia beat frequency in vitro

“…Although low doses of lignocaine do not affect ciliary beat frequency in vitro [18], 2 % lignocaine has been shown lo cause ciliostasis in human nasal biopsy specimens [19]. Atropine is known to inhibit mucus transport rates in humans [20]; however, this appears to be caused by inhibition of mucus secretion and there is little direct evidence for a depressant effect on the cilia [21].…”

Importance of airway blood flow on particle clearance from the lung

“…Particle delivery and clearance measurements. The technique to measure the distribution of insoluble radioactive particles deposited in the lung and their subsequent clearance as a gauge of airway mucociliary transport by gammacamera imaging has been described previously (17). 99m Tclabeled sulfur colloid particles were generated as an aerosol by jet nebulizer and delivered through the tracheal tube during tidal breathing.…”

“…To verify the labeling procedures, 99m Tc-labeled sulfur colloid was sampled from the nebulizer reservoir postnebulization to assay for unbound 99m Tc by using silica gel media and thin-layer chromatography (6). This radiomarker has been shown to be stable throughout a 24-h postinhalation period in human subjects (17). To standardize the delivery and dose of aerosols, a dosimeter (Spira-Elektra-2; Respiratory Care Center, Hameenlinnan, Finland), which delivered aerosol only during the inspiratory cycle of a tidal breath, was attached to the nebulizer (Devilbiss no.…”