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肺腺泡树三维空间填充模型中的呼吸流现象和重力沉积

Respiratory flow phenomena and gravitational deposition in a three-dimensional space-filling model of the pulmonary acinar tree.

作者信息

Sznitman Josué, Heimsch Thomas, Wildhaber Johannes H, Tsuda Akira, Rösgen Thomas

机构信息

Institute of Fluid Dynamics, ETH Zurich, CH-8092 Zurich, Switzerland.

出版信息

J Biomech Eng. 2009 Mar;131(3):031010. doi: 10.1115/1.3049481.

Abstract

The inhalation of micron-sized aerosols into the lung's acinar region may be recognized as a possible health risk or a therapeutic tool. In an effort to develop a deeper understanding of the mechanisms responsible for acinar deposition, we have numerically simulated the transport of nondiffusing fine inhaled particles (1 mum and 3 microm in diameter) in two acinar models of varying complexity: (i) a simple alveolated duct and (ii) a space-filling asymmetrical acinar branching tree following the description of lung structure by Fung (1988, "A Model of the Lung Structure and Its Validation," J. Appl. Physiol., 64, pp. 2132-2141). Detailed particle trajectories and deposition efficiencies, as well as acinar flow structures, were investigated under different orientations of gravity, for tidal breathing motion in an average human adult. Trajectories and deposition efficiencies inside the alveolated duct are strongly related to gravity orientation. While the motion of larger particles (3 microm) is relatively insensitive to convective flows compared with the role of gravitational sedimentation, finer 1 microm aerosols may exhibit, in contrast, complex kinematics influenced by the coupling between (i) flow reversal due to oscillatory breathing, (ii) local alveolar flow structure, and (iii) streamline crossing due to gravity. These combined mechanisms may lead to twisting and undulating trajectories in the alveolus over multiple breathing cycles. The extension of our study to a space-filling acinar tree was well suited to investigate the influence of bulk kinematic interaction on aerosol transport between ductal and alveolar flows. We found the existence of intricate trajectories of fine 1 microm aerosols spanning over the entire acinar airway network, which cannot be captured by simple alveolar models. In contrast, heavier 3 microm aerosols yield trajectories characteristic of gravitational sedimentation, analogous to those observed in the simple alveolated duct. For both particle sizes, however, particle inhalation yields highly nonuniform deposition. While larger particles deposit within a single inhalation phase, finer 1 microm particles exhibit much longer residence times spanning multiple breathing cycles. With the ongoing development of more realistic models of the pulmonary acinus, we aim to capture some of the complex mechanisms leading to deposition of inhaled aerosols. Such models may lead to a better understanding toward the optimization of pulmonary drug delivery to target specific regions of the lung.

摘要

将微米级气溶胶吸入肺部腺泡区域可能被视为一种潜在的健康风险或一种治疗手段。为了更深入地了解导致腺泡沉积的机制,我们对直径为1微米和3微米的非扩散性细吸入颗粒在两种不同复杂程度的腺泡模型中的传输进行了数值模拟:(i)一个简单的肺泡化管道;(ii)一个按照冯(1988年,《肺结构模型及其验证》,《应用生理学杂志》,第64卷,第2132 - 2141页)对肺结构的描述构建的空间填充不对称腺泡分支树。针对平均成年人体的潮式呼吸运动,研究了在不同重力方向下详细的颗粒轨迹、沉积效率以及腺泡流动结构。肺泡化管道内的轨迹和沉积效率与重力方向密切相关。虽然与重力沉降作用相比,较大颗粒(3微米)的运动对对流流动相对不敏感,但相比之下,更细的1微米气溶胶可能表现出复杂的运动学,这受到以下因素耦合的影响:(i)振荡呼吸导致的流动逆转;(ii)局部肺泡流动结构;(iii)重力引起的流线交叉。这些综合机制可能导致在多个呼吸周期中肺泡内的轨迹扭曲和起伏。我们将研究扩展到空间填充腺泡树,非常适合研究整体运动相互作用对导管和肺泡流之间气溶胶传输的影响。我们发现存在跨越整个腺泡气道网络的1微米细气溶胶的复杂轨迹,这是简单肺泡模型无法捕捉到的。相比之下,较重的3微米气溶胶产生的轨迹具有重力沉降特征,类似于在简单肺泡化管道中观察到的轨迹。然而,对于这两种粒径的颗粒,吸入颗粒都会产生高度不均匀的沉积。较大颗粒在单次吸入阶段就会沉积,而更细的1微米颗粒则表现出跨越多个呼吸周期的长得多的停留时间。随着更逼真的肺腺泡模型不断发展,我们旨在捕捉一些导致吸入气溶胶沉积的复杂机制。这样的模型可能有助于更好地理解如何优化肺部药物输送以靶向肺部特定区域。

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