title: Effect of the route and mode of agonist delivery on functional behaviour of the airways.
abstract: There is evidence that the mode of smooth muscle agonist delivery affects the changes induced in lung mechanical properties. The object of this investigation was to study modifications in airway behaviour associated with different modes of agonist delivery. Tracheal (Ptr) and alveolar pressure (PA) and flow (V) were measured in open-chested, mechanically ventilated (f = 1 Hz, VT = 10 ml/kg, PEEP = 4 cm H2O) rats under baseline conditions and during administration of repeated intravenous (i.v.) bolus, i.v. continuous infusion and aerosols of methacholine (MCh). We calculated lung elastance (EL) and lung resistance (RL) by fitting the equation of motion to changes in Ptr and V. We assessed the patency of the airway pathways and local dynamic hyperinflation by comparing Ptr vs PA. Comparison of the three different modes of MCh delivery showed a difference in the functional behaviour of the airways. In the aerosol group a larger incidence of highly constricted airways was observed. Conversely, the i.v. groups showed a larger incidence of regional dynamic hyperinflation. In the bolus group a different time course in the development of dynamic hyperinflation was observed for different pathways within the same animal. For consecutive challenges a given pathway tended to behave in the same manner, suggesting the response was characteristic for that pathway. In this study we have shown that, even though different airway pathways show different intrinsic reactivity, the mode of agonist delivery plays a role in determining functional airway behaviour.
authors.affiliation: Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, Quebec, Canada.
authors.forename: F G
authors.initials: FG
authors.lastname: Salerno
authors.forename: M S
authors.initials: MS
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004333:Drug Administration Routes; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage*; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011312:Pressure; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D015656:Respiratory Mechanics / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000502:physiology
chemical_list: D018721:Muscarinic Agonists; D016210:Methacholine Chloride