Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages
Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages
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DOI：
10.1006/taap.1997.8206
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发表时间：
1997-08-01
影响因子：
3.8
通讯作者：
Morgan, KT
中科院分区：
文献类型：
--
作者：
Kimbell, JS;Godo, MN;Morgan, KT
来自实验室动物实验的数据通常用于设定人类暴露于吸入材料的安全水平的指南，F344大鼠已被广泛用于实验室实验，以确定暴露于鼻道中吸入材料的影响。许多吸入的物质在大鼠鼻道的嗅觉（后部）区域诱导毒性反应。主要气流路径的位置已被认为在确定某些嗅觉损伤位置模式中起主导作用。由于鼻气流模式在物种之间显著不同，因此需要方法来评估这些差异可能显著影响将动物中局部剂量的影响外推至人类中潜在疾病结果的条件。气流和吸入气体摄取的计算流体动力学模型已用于预测前F344大鼠鼻通道中气道壁的剂量（Kimbell等人，毒理学.应用药理学，一九九三年; 121，253-263），为了确定鼻气流模式在影响嗅觉病变分布中的作用，将该模型扩展到包括嗅觉区域。使用F344大鼠鼻通道的连续步骤组织切片来构建计算机模型。整个大鼠鼻通道的吸气气流的模拟与先前报道的实验数据一致，存在于前鼻中的五个主要模拟气流中的四个（背侧、中间、腹侧和腹侧内侧流）一起流动以在鼻咽管腹侧离开，绕过筛窦凹。当从矢状面观察时，剩余的背内侧流分裂，以Z形模式向内侧和外侧流过嗅觉上皮内衬的筛下窝。在筛窦隐窝中的模拟流动比鼻通道的前部和腹侧部分中的流动慢一个数量级以上。当鼻前庭被重塑为向上翻时，预测背内侧流中的流量会略高，并且随着吸气气流速率的增加，更多的流量被分配给背内侧流，这表明大鼠可以通过改变鼻前庭的形状和增加吸气气流速度来分配更多的气流。本研究首次描述了F344大鼠鼻复杂嗅区的气流，该模型将用于评估气流模式在确定异源性诱导的嗅粘膜病变分布中的作用。这些信息，结合模型的处置在气道衬里，将提供全面的剂量学模型外推动物对人类的反应数据。(C)北京：科学出版社.
Data from laboratory animal experiments are often used in setting guidelines for safe levels of human exposure to inhaled materials, The F344 rat has been used extensively in laboratory experiments to determine effects of exposure to inhaled materials in the nasal passages. Many inhaled materials induce toxic responses in the olfactory (posterior) region of the rat nasal passages. The location of major airflow routes has been proposed as playing a dominant role in determining some olfactory lesion location patterns. Since nasal airflow patterns differ significantly among species, methods are needed to assess conditions under which these differences may significantly affect extrapolation of the effects of local dose in animals to potential disease outcome in humans, A computational fluid dynamics model of airflow and inhaled gas uptake has been used to predict dose to airway walls in the anterior F344 rat nasal passages (Kimbell et al., Toxicol. Appl. Pharmacol., 1993; 121, 253-263), To determine the role of nasal airflow patterns in affecting olfactory lesion distribution, this model was extended to include the olfactory region. Serial-step histological sections of the nasal passages of a F344 rat were used to construct the computer model. Simulations of inspiratory airflow throughout the rat nasal passages were consistent with previously reported experimental data, Four of the five major simulated flow streams present in the anterior nose (dorsal lateral, middle, ventral lateral, and ventral medial streams) flowed together to exit ventrally at the nasopharyngeal duct, bypassing the ethmoid recesses. The remaining dorsal medial stream split to flow both medially and laterally through the olfactory-epithelium-lined ethmoid recesses in a Z-shaped pattern when viewed sagitally. Simulated flow in the ethmoid recesses was more than an order of magnitude slower than flow in the anterior and ventral parts of the nasal passages. Somewhat higher volumes of flow were predicted in the dorsal medial stream when the nasal vestibule was reshaped to be upturned, and more flow was allocated to the dorsal medial stream with increased inspiratory airflow rate, suggesting that rats may be able to allocate more airflow to this stream by both modifying the shape of the nasal vestibule and increasing inhaled air velocity during sniffing, The present study provides the first description of flow in the complex olfactory region of the nose of the F344 rat, This model will be used to evaluate the role of airflow patterns in determining the distribution of xenobiotically induced olfactory mucosal lesions. This information, combined with models of disposition in the airway lining, will provide comprehensive dosimetry models for extrapolating animal response data to humans. (C) 1997 Academic Press.