Lining fluid flow and surfactant transport during the unsteady opening of pulmonary airways and alveoli

肺气道和肺泡不稳定开放期间的内衬流体流动和表面活性剂输送

• 批准号: 9978605
• 负责人: Donald Gaver
• 金额: $ 28.69万
• 依托单位: Tulane University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9978605&HistoricalAwards=false
• 关键词: Lining; fluid; flow; surfactant; transport

9978605GaverAt birth, a newborn infant's lungs are liquid-filled and must be inflated from a collapsed state to initiate breathing. For healthy infants, a modest inspiratory effort introduces air into the lung so that the atmosphere can directly communicate with alveoli, the primary site of gas-exchange with blood. Gestationally mature lungs release surfactant that decreases the effort necessary to inflate the lung. However, premature infants may lack adequate surfactant, increasing the surface tension. Surfactant insufficiency coupled with the extremely small size of the lung results in a large inspiratory effort necessary to inflate the premature lung, leading to airway atelectasis (extensive collapse of portions of the lung), deranged pulmonary mechanical responses, poor ventilation/perfusion relationships and insufficient alveolar ventilation. These premature airways could be opened by high pressure from a mechanical ventilator, however this damages the sensitive epithelial cells that line the airway walls, resulting in respiratory distress syndrome (RDS). Surfactant replacement therapy (SRT), initiated in the late 1980's, has dramatically reduced the number of fatalities associated with this disease. Refinements in exogenous surfactant composition continue to improve the outcome of RDS infants. Nevertheless, RDS remains the fourth leading cause of death of premature infants in the United States.The goal of the proposed research is to develop integrated models of pulmonary mechanical behavior coupled to surfactant physicochemical interactions. We intend to take advantage of our understanding of surfactant physicochemical properties and fluid-structure interactions to identify surfactant properties that may protect the lung from RDS. Additionally, we will attempt to use the large disparity between surfactant adsorption and desorption rates and the creation of surfactant multi-layers to specify ventilation parameters that will actively enhance surfactant concentration and thus optimize the opening of pulmonary airways. We anticipate that these models will allow us to predict surfactant properties and ventilation scenarios that will be useful in improving the outcome of infants afflicted with RDS.

9978605 Gaver出生时，新生儿的肺部充满液体，必须从塌陷状态充气才能开始呼吸。 对于健康的婴儿，适度的吸气努力将空气引入肺部，使得大气可以直接与肺泡连通，肺泡是与血液进行气体交换的主要部位。 妊娠期成熟的肺释放表面活性物质，减少肺膨胀所需的努力。 然而，早产儿可能缺乏足够的表面活性剂，增加了表面张力。 表面活性剂不足加上肺的极小尺寸导致使过早的肺膨胀所需的大的吸气努力，导致气道肺不张（肺的部分的广泛塌陷）、紊乱的肺机械响应、不良的通气/灌注关系和不充分的肺泡通气。 这些过早的气道可以通过机械呼吸机的高压打开，但是这会损害气道壁的敏感上皮细胞，导致呼吸窘迫综合征（RDS）。 表面活性剂替代疗法（SRT），开始于20世纪80年代后期，已大大减少了与这种疾病相关的死亡人数。 外源性表面活性剂成分的改进继续改善RDS婴儿的结局。 尽管如此，RDS仍然是美国早产儿死亡的第四大原因，本研究的目的是建立肺机械行为与表面活性剂物理化学相互作用的综合模型。 我们打算利用我们对表面活性剂的物理化学性质和流体-结构相互作用的理解来确定可能保护肺免受RDS的表面活性剂性质。 此外，我们将尝试使用表面活性剂吸附和解吸速率之间的巨大差异以及表面活性剂多层的创建来指定通气参数，这些参数将积极提高表面活性剂浓度，从而优化肺气道的开放。 我们预计，这些模型将使我们能够预测表面活性剂的性质和通气情况，这将有助于改善患有RDS的婴儿的结果。