Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human
Comparative Computational Modeling of Airflows and Vapor Dosimetry in the Respiratory Tracts of Rat, Monkey, and Human
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DOI：
10.1093/toxsci/kfs168
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发表时间：
2012-08-01
影响因子：
3.8
通讯作者：
Einstein, Daniel R.
中科院分区：
文献类型：
--
作者：
Corley, Richard A.;Kabilan, Senthil;Einstein, Daniel R.
计算流体动力学（CFD）模型可用于预测呼吸道中空气传播物质的特定部位剂量，并阐明解剖学、生理学和呼吸模式中物种差异的重要性。我们改进了成像和模型开发方法，使大鼠、猴子和人类的CFD模型现在涵盖了从鼻子或嘴巴到肺部的气道。在大鼠、猴和人模型中分别包括总共1272、2172和135个肺气道，代表17 +/- 7、19 +/- 9或9 +/- 2代气道。一个CFD/生理为基础的药代动力学模型先前开发的丙烯醛适应这些解剖学正确的扩展气道模型。模型参数从文献中获得或直接测量。在稳态吸入条件下确定气流和丙烯醛摄取模式，以提供与先前数据和仅经鼻模拟的直接比较。结果证实，区域吸收是敏感的气道几何形状，气流速度，丙烯醛浓度，空气：组织分配系数，组织厚度，和最大代谢率。预计大鼠的鼻提取效率最高，其次是猴，然后是人。对于人类的鼻和口呼吸模式，预测较低的气管支气管组织的摄取率高于大鼠或猴。这些扩展的气道模型提供了一个独特的基础，比较材料运输和特定部位的组织吸收在一个显着更大的范围内进行气道在大鼠，猴子，和人类比以前的CFD模型。
Computational fluid dynamics (CFD) models are useful for predicting site-specific dosimetry of airborne materials in the respiratory tract and elucidating the importance of species differences in anatomy, physiology, and breathing patterns. We improved the imaging and model development methods to the point where CFD models for the rat, monkey, and human now encompass airways from the nose or mouth to the lung. A total of 1272, 2172, and 135 pulmonary airways representing 17 +/- 7, 19 +/- 9, or 9 +/- 2 airway generations were included in the rat, monkey and human models, respectively. A CFD/physiologically based pharmacokinetic model previously developed for acrolein was adapted for these anatomically correct extended airway models. Model parameters were obtained from the literature or measured directly. Airflow and acrolein uptake patterns were determined under steady-state inhalation conditions to provide direct comparisons with prior data and nasal-only simulations. Results confirmed that regional uptake was sensitive to airway geometry, airflow rates, acrolein concentrations, air:tissue partition coefficients, tissue thickness, and the maximum rate of metabolism. Nasal extraction efficiencies were predicted to be greatest in the rat, followed by the monkey, and then the human. For both nasal and oral breathing modes in humans, higher uptake rates were predicted for lower tracheobronchial tissues than either the rat or monkey. These extended airway models provide a unique foundation for comparing material transport and site-specific tissue uptake across a significantly greater range of conducting airways in the rat, monkey, and human than prior CFD models.