title: Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats.
abstract: We examined the effects of elastase-induced emphysema on lung volumes, pulmonary mechanics, and airway responses to inhaled methacholine (MCh) of nine male Brown Norway rats. Measurements were made before and weekly for 4 wk after elastase in five rats. In four rats measurements were made before and at 3 wk after elastase; in these same animals the effects of changes in end-expiratory lung volume on the airway responses to MCh were evaluated before and after elastase. Airway responses were determined from peak pulmonary resistance (RL) calculated after 30-s aerosolizations of saline and doubling concentrations of MCh from 1 to 64 mg/ml. Porcine pancreatic elastase (1 IU/g) was administered intratracheally. Before elastase RL rose from 0.20 +/- 0.02 cmH2O.ml-1.s (mean +/- SE; n = 9) to 0.57 +/- 0.06 after MCh (64 mg/ml). A plateau was observed in the concentration-response curve. Static compliance and the maximum increase in RL (delta RL64) were significantly correlated (r = 0.799, P less than 0.01). Three weeks after elastase the maximal airway response to MCh was enhanced and no plateau was observed; delta RL64 was 0.78 +/- 0.07 cmH2O.ml-1.s, significantly higher than control delta RL64 (0.36 +/- 0.7, P less than 0.05). Before elastase, increase of end-expiratory lung volume to functional residual capacity + 1.56 ml (+/- 0.08 ml) significantly reduced RL at 64 mg MCh/ml from 0.62 +/- 0.05 cmH2O.ml-1.s to 0.50 +/- 0.03, P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Bellofiore
authors.forename: D H
authors.initials: DH
authors.lastname: Eidelman
authors.forename: P T
authors.initials: PT
authors.lastname: Macklem
authors.forename: J G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D004646:Emphysema / Q000503:physiopathology*; D008170:Lung Compliance / Q000187:drug effects; D008176:Lung Volume Measurements; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology
chemical_list: D008688:Methacholine Compounds; D016210:Methacholine Chloride; D010196:Pancreatic Elastase