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.

Effects of propofol on bronchoconstriction and bradycardia induced by vagal nerve stimulation

“…Hence, baroreflex‐mediated sympathetic nervous system stimulation may attenuate VNS‐induced bronchoconstriction via increased circulating catecholamines. However, as we have previously reported that propofol significantly decreased plasma catecholamine levels during histamine‐ (5) and methacholine‐induced (6) hypotension we feel that propofol‐mediated activation of the sympathetic nervous system is unlikely and therefore this is also unlikely to explain the observed bronchodilation.…”

“…Brown et al also demonstrated in sheep that propofol attenuates neurally mediated bronchoconstriction with a minimal direct effect on airway smooth muscle contraction (17). However, using the same bronchoscopic method, we have demonstrated that propofol attenuated methacholine‐induced bronchoconstriction in dogs both with and without vagotomy (6). In that study, methacholine produced an approximate 50% decrease in BCA and 20 mg/kg propofol attenuated this effect to only 25%.…”

“…P revious clinical investigations have suggested that propofol possesses bronchoprotective properties (1–4). Using a bronchoscopic method, we have also demonstrated that propofol reduces basal airway tone and histamine‐ (5) and methacholine‐induced (6) bronchoconstriction in dogs (7). However, the mechanism(s) underlying this spasmolytic effect are poorly understood.…”

Propofol Preferentially Relaxes Neurokinin Receptor-2-induced Airway Smooth Muscle Contraction in Guinea Pig Trachea

“…Calcium sensitivity in permeabilized canine tracheal smooth muscle cells in the absence or presence of muscarinic receptor activation was not effected by propofol even at concentrations of 270 μM. 35 In dogs propofol attenuated methacholine bronchoconstriction, 36 the neural component of histamine-induced bronchoconstriction 2 and vagal nerve-induced bronchoconstriction 4 only at concentrations of 20mg/kg propofol (typical human induction dose is 2-3 mg/kg). Taken together, these studies have demonstrated that at clinically relevant concentrations, propofol does not have significant effects on cholinergic modulation of airway smooth muscle.…”

Guideline-oriented perioperative management of patients with bronchial asthma and chronic obstructive pulmonary disease

“…The mechanism involves direct or vagally mediated relaxation of airway smooth muscle [136][137][138][139][140]. Barbiturates, as compared to propofol, produce weaker inhibition of airway contraction [141,142], and when used alone, may actually induce airway smooth muscle contraction [9].…”