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Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation
Author(s) -
Cairncross Alvenia,
Noble Peter B.,
McFawn Peter K.
Publication year - 2018
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.13271
Subject(s) - bronchodilation , medicine , dynamic hyperinflation , contraction (grammar) , copd , hyperinflation , lung volumes , acetylcholine , cardiology , lung , anesthesia , bronchodilator , asthma , monetary policy , economics , monetary economics
Background and objective Lung hyperinflation and reduced bronchodilation to deep inspiration (DI) are features of chronic obstructive pulmonary disease (COPD). Hyperinflation might impair the ability of a DI to stretch airway smooth muscle (ASM), as the bronchi operate at a stiff region of the pressure–volume curve. Methods Bronchial segments from pig lungs were mounted in an organ bath and equilibrated at either 5 cm H 2 O (control) or 20 cm H 2 O (hyperinflated) transmural pressure (P tm ). Cumulative dose–response curves to acetylcholine (ACh) were performed to determine maximal response (E max ) and sensitivity under static conditions (fixed P tm ) or during simulated breathing (Δ10 cm H 2 O P tm at 0.25 Hz). The effect of hyperinflation on ASM contraction was further examined in bronchial rings contracted at a short ASM length (reference length, L ref ) or stretched by an additional 30% (length 1.3 times the L ref , 1.3L ref ). Results Oscillatory loads halved E max from 61.0 ± 3.8 to 29.7 ± 4.4 cm H 2 O ( P < 0.0001) in control bronchial segments, but only from 40.0 ± 2.5 to 31.2 ± 2.4 cm H 2 O ( P < 0.05) in hyperinflated segments. The percentage reduction in active pressure with oscillation was less in hyperinflated compared with control segments ( P < 0.01). Sensitivity was not altered by oscillation in either hyperinflated or control segments; however, hyperinflated segments were more sensitive ( P < 0.05). The effect of inflation on sensitivity was confirmed using bronchial rings where stretched rings were more sensitive than unstretched rings ( P < 0.01). Conclusion Hyperinflated bronchi exhibit reduced bronchodilation to breathing and increased sensitivity to bronchoconstrictor stimuli. Findings suggest that hyperinflation may directly alter airway function by reducing the protective effects of DI and initiating contraction at low doses of contractile stimuli.