Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
J Appl Physiol (1985). 2013 Aug 15;115(4):436-45. doi: 10.1152/japplphysiol.00009.2013. Epub 2013 May 30.
Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5-10 cmH2O) imposed 4.9 ± 2.0% strain and resulted in 11.6 ± 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5-30 cmH2O) achieved 62.9 ± 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm = 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.
由于呼吸而施加在气道平滑肌上的脉动力量被认为可以调节体内的高反应性。然而,最近的动物和人体离体气道研究表明,典型的呼吸大小的跨壁压(Ptm)围绕固定平均值的振荡在减轻气道收缩方面效果不佳。为了帮助理解这种差异,我们假设能够产生与在气道平滑肌条带研究中观察到的相同程度的支气管扩张的 Ptm 振荡需要施加大于体内预期发生的应变。首先,我们将越来越大的 Ptm 振荡幅度施加到一个从模拟正常功能残气量为 5cmH2O 的 Ptm 静态收缩的气道上。潮汐样振荡(5-10cmH2O)施加 4.9±2.0%应变,导致 11.6±4.8%恢复,而模拟每次呼吸深吸气的 Ptm 振荡(5-30cmH2O)实现了 62.9±12.1%的恢复。然后,我们从 Ptm = 1cmH2O 开始应用相同的 Ptm 振荡,导致每个振荡幅度的应变增加约一倍。当施加极端应变时,我们观察到完全恢复。将两个数据集结合起来,我们发现应变与恢复结果之间存在线性关系。最后,我们比较了收缩前和收缩后 Ptm 振荡对狭窄的影响,以及仅在收缩后施加 Ptm 振荡的影响,发现这两种加载条件对狭窄的影响相似。我们的结论是,虽然施加到气道壁上的足够大的应变能够产生显著的支气管扩张,但实现这些应变所需的 Ptm 振荡预计不会在体内发生。