Engineering Ventilation Waveforms to Reduce Atelectrauma

设计通气波形以减少肺损伤

• 批准号: 7417877
• 负责人: DONALD P. GAVER
• 金额: $ 34.89万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7417877
• 关键词: Address; Adult; Adult Respiratory Distress Syndrome; Air; Alveolus; Asthma; Atelectasis; Behavior; Biological; Biological Models; Blood capillaries; Cells; Closure; Computer Simulation; Coupled; Couples; Cultured Cells; Disease; Engineering; Environmental air flow; Epithelial; Epithelial Cells; Epithelium; Excision; Experimental Models; Fingers; Frequencies; Gases; Goals; Infant Mortality; Laboratories; Lead; Liquid substance; Lung; Mechanical Stress; Mechanics; Modeling; Modification; Newborn Respiratory Distress Syndrome; Obstruction; Perfusion; Property; Protocols documentation; Pulmonary Surfactants; Pulsatile Flow; Range; Recruitment Activity; Replacement Therapy; Research Personnel; Response to stimulus physiology; Role; Rupture; Staging; Stimulus; Stress; Stretching; Structure; Surface Tension; System; Testing; Tissues; Tube; Ventilator; Ventilator-induced lung injury; airway epithelium; atelectrauma; capillary; cell injury; design; fluid flow; improved; insight; interfacial; lung injury; migration; mortality; pressure; programs; research study; response; surfactant; surfactant deficiency

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.

描述（由申请人提供）：该项目的目标是确定有前途的低容量通气波形，该波形将打开闭塞的肺气道，同时对敏感上皮组织的损害最小。这个问题具有重要的生理意义，因为粘性液体闭塞导致的肺气道阻塞发生在多种疾病中，包括呼吸窘迫综合征(RDS)、急性呼吸窘迫综合征(ARDS)和哮喘。气道关闭因气体输送减少而导致通气-灌注不匹配，从而导致死亡率增加。在 RDS 和潜在的 ARDS 中，由于表面活性剂缺乏，内层液体表面张力升高，从而增加了打开闭塞气道所需的压力。拟议的研究将检验这样的假设：脉动通气波形可通过最大化表面活性剂转运和优化生物物理反应来减少对气道上皮施加的破坏性机械应力，从而最大限度地减少对气道上皮细胞的损伤。每个具体目标都将计算模拟与实验室实验相结合，以阐明手指空气通过作为模型系统的圆柱形管迁移过程中机械应力、传输特性、表面活性剂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：测试上皮细胞因气道重新开放期间扫过细胞的瞬时压力梯度而受伤的预测，并确定稳定和脉动流的刺激/响应行为。具体目标#2：研究与界面流动波形相结合的表面活性剂生物物理特性可以保护上皮的预测，并使用从这些研究中得出的原理来预测通气波形的特性，该特性将招募阻塞的气道，同时对气道上皮的损害最小。该项目的成功完成将有助于更好地了解通气对肺损伤的作用。根据本研究得出的原理改进的通气方案可以降低患有呼吸窘迫综合征或哮喘的婴儿和成人的死亡率。