title: Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.
abstract: We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, University of Chicago, Illinois 60637.
authors.forename: D W
authors.initials: DW
authors.lastname: Ray
authors.forename: C
authors.initials: C
authors.lastname: Hernandez
authors.forename: N
authors.initials: N
authors.lastname: Munoz
authors.forename: A R
authors.initials: AR
authors.lastname: Leff
authors.forename: J
authors.initials: J
authors.lastname: Solway
mesh_terms: D000403:Airway Resistance; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D001980:Bronchi / Q000503:physiopathology*; D003251:Constriction, Pathologic; D006168:Guinea Pigs; D007700:Kinetics; D008170:Lung Compliance; D008297:Male; D012119:Respiration; D014628:Vagotomy
chemical_list: D001285:Atropine