Dynamic airway constriction in rats: heterogeneity and response to deep inspiration.
Dynamic airway constriction in rats: heterogeneity and response to deep inspiration.
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大鼠动态气道收缩：异质性和对深吸气的反应。
DOI：
10.1152/ajplung.00050.2019
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Waters,ChristopherM
中科院分区：
文献类型：
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作者：
Phung,Thien-KhoiN;Sinclair,ScottE;Makena,Patrudu;Molthen,RobertC;Waters,ChristopherM
高反应性导致的气道狭窄严重限制了哮喘患者的气体交换。对人类和动物的成像研究表明，支气管收缩会导致整个肺部的片状通气缺陷，几个计算模型预测这些区域是由于较小气道的收缩。然而，这些成像方法在捕获小气道中的动态变化的能力方面通常是有限的，并且收缩的模式是异质的。为了直接研究气道狭窄的区域变化和对深吸气（DI）的反应，我们利用钽尘和大鼠肺的微焦点X射线成像来获得完整动物模型中气道的动态图像。使用flexiVent系统同时测量气道阻力。使用定制开发的软件跟踪气道直径的变化，直至第19代（~0.3-3 mm）。然后测量支气管收缩过程中对乙酰甲胆碱（MCh）激发的反应。与模型预测相反，我们观察到在较大气道中响应于MCh激发的显著更大的收缩百分比。尽管MCh的总呼吸阻力呈剂量依赖性增加，但气道直径的百分比变化与剂量增加相似。MCh后的单次DI导致阻力显著降低，但未导致气道直径显著增加。然而，多次DI确实导致气道直径显著增加。这些测量使我们能够直接量化支气管收缩期间气道的动态变化，并证明较大气道的收缩更大。
Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up togeneration 19(~0.3–3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.