title: Airway Bistability Is Modulated by Smooth Muscle Dynamics and Length-Tension Characteristics.
abstract: 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.
authors.affiliation: Department of Mathematics, University of Auckland, Auckland, New Zealand. Electronic address: g.donovan@auckland.ac.nz.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Donovan
mesh_terms: D008954:Models, Biological; D009130:Muscle, Smooth / Q000502:physiology*; D011312:Pressure; D012143:Respiratory Physiological Phenomena