Dowie Jackson, Ansell Thomas K, Noble Peter B, Donovan Graham M
Department of Mathematics, University of Auckland, New Zealand.
School of Veterinary and Life Sciences, Murdoch University, Australia; School of Anatomy, Physiology and Human Biology, The University of Western Australia, Australia.
Respir Physiol Neurobiol. 2016 Jan;220:25-32. doi: 10.1016/j.resp.2015.09.006. Epub 2015 Sep 12.
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.
长度适应性是在气道平滑肌(ASM)中观察到的一种现象,随着时间的推移,长度-张力曲线会发生偏移。长度适应性有可能在哮喘的气道收缩和气道高反应性中发挥重要作用。安塞尔等人在2015年(《应用生理学杂志》2014年,10.1152/japplphysiol.00724.2014)的最新研究结果对这一作用提出了质疑,他们使用完整的气道标本而非气道平滑肌条来测试长度适应性。通过这种技术,他们在完整气道中未发现长度适应性的证据。在此,我们试图通过构建一个完整气道的最小数学模型来解决这一明显的差异,该模型包括遵循经典长度-张力曲线并经历长度适应性变化的气道平滑肌。这使我们能够表明:(1)在大的、有软骨的完整气道中不应预期有长度适应性的证据;(2)即使在顺应性高的外周气道中,或在大气道压力-容积曲线的更顺应性区域,长度适应性的影响也将是适度的,并且在完整气道中充其量只能勉强检测到;(3)控制完整气道中长度适应性表现的关键参数是气道顺应性和松弛时间尺度。这种数学模拟的结果表明,在分离的气道平滑肌水平观察到的长度适应性可能不会在正常完整气道中明显表现出来。