title: Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips.
abstract: Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways; (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways; (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway.
authors.affiliation: Department of Mathematics, University of Auckland, New Zealand.
authors.forename: Jackson
authors.initials: J
authors.lastname: Dowie
authors.affiliation: School of Veterinary and Life Sciences, Murdoch University, Australia; School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Ansell
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia; Centre for Neonatal Research and Education, The University of Western Australia, Australia.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Noble
authors.affiliation: Department of Mathematics, University of Auckland, New Zealand. Electronic address: g.donovan@auckland.ac.nz.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Donovan
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008955:Models, Cardiovascular; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000033:anatomy & histology / Q000502:physiology*; D009929:Organ Size; D012119:Respiration
keywords: Airway smooth muscle; Bronchi; Hyperresponsiveness; Length adaptation