Donovan Graham M
Department of Mathematics, University of Auckland, Auckland, New Zealand.
Biophys J. 2016 Nov 15;111(10):2327-2335. doi: 10.1016/j.bpj.2016.10.007.
Airway closure has important implications for lung disease, especially asthma; in particular, the prospect of bistability between open and closed (or effectively closed) airway states has been thought to play a prominent role in airway closure associated with the formation of clustered ventilation defects in asthma. However, many existing analyses of closure consider only static airway equilibria; here we construct, to our knowledge, a new model wherein airway narrowing and closure dynamics are modulated by coupling the airway to cross-bridge models of airway smooth muscle dynamics and force generation. Using this model, we show that important qualitative features of airway pressure-radius hysteresis loops are highly dependent on both airway smooth muscle dynamics, and the length-tension relationship. Furthermore, we show that two recent experimental results from intact bronchial segments are both expressions of the same phenomenon: that a monotonically increasing length-tension relationship, with sharply higher tension at longer lengths, is needed to drive the observed changes in low-compliance regions of the baseline pressure-radius curve. We also explore the potential implications of this finding for airway closure in coupled airway models.
气道关闭对肺部疾病,尤其是哮喘具有重要影响;特别是,气道开放与关闭(或有效关闭)状态之间的双稳态前景被认为在与哮喘中簇状通气缺陷形成相关的气道关闭中起着重要作用。然而,许多现有的关闭分析仅考虑静态气道平衡;在此,据我们所知,我们构建了一个新模型,其中气道变窄和关闭动力学通过将气道与气道平滑肌动力学和力产生的横桥模型耦合来调节。使用该模型,我们表明气道压力-半径滞后环的重要定性特征高度依赖于气道平滑肌动力学和长度-张力关系。此外,我们表明来自完整支气管节段的两个近期实验结果都是同一现象的表现:即需要单调增加的长度-张力关系,在更长长度处具有明显更高的张力,以驱动基线压力-半径曲线低顺应性区域中观察到的变化。我们还探讨了这一发现对耦合气道模型中气道关闭的潜在影响。
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