title: Comparison of relaxant effects of propofol on methacholine-induced bronchoconstriction in dogs with and without vagotomy.
abstract: Propofol has been suggested to have in vivo airway relaxant effects, although the mechanism is still unclear. In this study, we determined whether propofol could antagonize methacholine-induced bronchoconstriction and determined whether vagotomy modifies this relaxant effect. Fourteen mongrel dogs anaesthetized with pentobarbital and pancuronium were assigned to a control group (n=7) and a vagotomy group (n=7). The trachea was intubated with a special endotracheal tube that had a second lumen for insertion of the bronchoscope. Bronchial cross-sectional area, which was monitored continuously through the bronchoscope, was measured with image analysis software. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1) + 5.0 microg kg(-1) min(-1)) until the end of the experiment. Thirty minutes after the start of methacholine infusion, propofol 0, 0.2, 2.0 and 20 mg kg(-1) was administered. Changes in bronchial cross-sectional area were expressed as percentages of the basal area. Plasma concentrations of propofol and catecholamine were measured by high-performance liquid chromatography. Maximal inhibition (bronchoconstriction = 0%, baseline = 100%) and IC50 (concentration producing 50% inhibition of maximal effect) produced by propofol was obtained from each concentration-response curve using a curve-fitting program. Methacholine decreased bronchial cross-sectional area to 49.3% (95% confidence interval 38.5-60.1%) and 45.3% (34.8-55.7%) of the baseline value. Propofol 20 mg kg(-1) significantly reversed this effect: bronchial cross-sectional area was reduced to 77.8% (66.2-89.6%) and 75.9% (64.0-87.9) in the control and vagotomy groups respectively. The two groups did not differ significantly in the maximal inhibitory effect of propofol [control group, 61.1% (46.3-75.9%), vagotomy group, 64.2% (40.1-88.3%)] or pIC50 [control group 5.03 (4.55-5.51), vagotomy group 4.86 (4.49-5.24)]. Therefore, the relaxant effects of propofol on methacholine-induced bronchoconstriction may not be mediated centrally. Propofol may relax airway smooth muscles directly or through the peripheral vagal pathway.
authors.affiliation: Department of Anesthesiology, University of Hirosaki School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kabara
authors.forename: K
authors.initials: K
authors.lastname: Hirota
authors.forename: E
authors.initials: E
authors.lastname: Hashiba
authors.forename: H
authors.initials: H
authors.lastname: Yoshioka
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Matsuki
mesh_terms: D018686:Anesthetics, Intravenous / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology; D016085:Bronchoconstrictor Agents / Q000037:antagonists & inhibitors; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D016210:Methacholine Chloride / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000097:blood; D015742:Propofol / Q000097:blood / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D018686:Anesthetics, Intravenous; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009638:Norepinephrine; D015742:Propofol; D004837:Epinephrine