Engineering Ventilation Waveforms to Reduce Atelectrauma

描述(由申请人提供)：该项目的目标是确定有希望的低通气量波形，以最大限度地减少对敏感上皮组织的损害，打开闭塞的肺通道。这一问题在生理学上意义重大，因为粘性液体阻塞导致的肺呼吸道阻塞可发生在多种疾病中，包括呼吸窘迫综合征(RDS)、急性呼吸窘迫综合征(ARDS)和哮喘。由于气体输送减少，呼吸道关闭会导致呼吸-灌流不匹配，从而导致死亡。在RDS和潜在的ARDS中，由于表面活性物质缺乏，衬里液体表面张力升高，这增加了打开阻塞的呼吸道所需的压力。拟议的研究将检验这样一个假设，即脉动通风波形可以通过最大化表面活性物质的运输和优化生物物理反应来减少对呼吸道上皮细胞的损害，从而减少施加在呼吸道上皮细胞上的破坏性机械应力。每个特定的目标都将计算模拟与实验室实验相结合，以阐明作为模型系统的空气手指通过圆柱管迁移过程中机械应力、传输特性、表面活性生物物理反应和细胞损伤之间的相互作用。该项目的具体目标是：具体目标1：测试在呼吸道重新开放过程中横扫细胞的瞬时压力梯度会损伤上皮细胞的预测，并确定稳定和脉动流动的刺激/反应行为。具体目标#2：研究表面活性物质生物物理特性与界面流动波形结合可以保护上皮的预测，并使用这些研究得出的原理来预测通风波形的特性，该特性将在对呼吸道上皮损伤最小的情况下招募阻塞的气道。该项目的成功完成将使人们更好地了解呼吸机在肺损伤中的作用。根据这项研究得出的原则改进的通风方案可能会降低患有呼吸窘迫综合征或哮喘的婴儿和成年人的死亡率。

DESCRIPTION (provided by applicant): The goal of this project is to identify promising low-volume ventilation waveforms that will open occluded pulmonary airways with minimal damage to sensitive epithelial tissue. This problem is physiologically significant because the obstruction of pulmonary airways by a viscous liquid occlusion occurs in a variety of diseases including respiratory distress syndrome (RDS), acute respiratory distress syndrome (ARDS) and asthma. Airway closure contributes to mortality through ventilation-perfusion mismatch from reduced gas transport. In RDS and potentially ARDS, the lining fluid surface tension is elevated due to surfactant deficiency, which increases the pressure necessary to open the occluded airways. The proposed studies will test the hypothesis that pulsatile ventilation waveforms can be used to minimize damage to airway epithelial cells by maximizing surfactant transport and optimizing biophysical responses to reduce the damaging mechanical stress imparted on airway epithelium. Each specific aim couples computational simulations to laboratory experiments to elucidate the interactions between mechanical stresses, transport properties, surfactant biophysical responses and cell damage during the migration of a finger of air through a cylindrical tube as the model system. The specific aims of the project are: Specific Aim #1: Test the prediction that epithelial cells are wounded by the transient pressure gradient that sweeps across the cells during airway reopening and determine the stimulus/response behavior for steady and pulsatile flows. Specific Aim #2: Investigate the prediction that surfactant biophysical properties coupled to interfacial flow waveforms can protect the epithelium, and use the principles derived from these studies to predict properties of ventilation waveforms that will recruit an obstructed airway with minimal damage to the airway epithelium. Successful completion of this project will lead to improved understanding of the role of ventilation on lung injury. Improved ventilation protocols resulting from the principles derived from this study could lead to reduced mortality of infants and adults suffering from respiratory distress syndrome or asthma.