ALVEOLAR SURFACE FORCES EFFECTS ON LUNG FUNCTION

描述（改编自申请人的摘要）：本提案侧重于 组织力和表面力的相互作用， 肺中的气液界面，以及这些如何决定 导致正常功能或功能障碍的微结构环境 实质力学、气体交换、肺毛细血管力学，以及 表面活性剂替代疗法。 这些问题尤其重要， 建立病理生理学的基本机制， 新生儿和成人呼吸窘迫的差异，以及为什么这些 差异导致表面活性剂替代的显著不同的功效 疗法 肺毛细血管顺应性对血流的影响是非常重要的 在肺中的分布，以及运输和隔离 白细胞是炎症的普遍成分。 实验将 在麻醉绵羊和离体肺中进行，表面张力 生理盐水灌洗引起的变化，用恒定表面张力冲洗 油和体内给予油酸。 结果将确立 急性肺损伤影响的方式：肺泡的几何形状和 肺泡管、实质稳定性、区域不均匀性导致 气体交换差和毛细机械。 该提案利用了 扩散光散射（DLS）的新技术，其中 肺表面积与体积比、毛细血管血容量和毛细血管 可以评估氧合。 DLS是独一无二的，因为它可以应用于 在体内和不固定的切除制备物中;它是肺的“窗口” 力学和气体交换迄今为止无法用于研究在这两个健康 和疾病

DESCRIPTION (Adapted from the applicant's abstract): This proposal focuses on the interplay of tissue forces and surface forces arising at the air-liquid interface in the lung, and how these determine the microstructural environment leading to normal function or dysfunction of parenchymal mechanics, gas exchange, pulmonary capillary mechanics, and surfactant replacement therapy. These questions are especially important in establishing the fundamental mechanisms underlying the pathophysiologic differences in respiratory distress of newborns and adults, and why these differences lead to strikingly different efficacy of surfactant replacement therapy. Pulmonary capillary compliance is important to blood flow distribution in the lung, and to the transit and sequestration of leukocytes, a ubiquitous component of inflammation. Experiments will be done in anesthetized sheep and in excised lungs with surface tension alterations caused by saline lavage, rinses with constant surface tension oils, and oleic acid administration in vivo. The results will establish the manner in which acute lung injury influences: the geometry of alveoli and alveolar ducts, parenchymal stability, regional inhomogeneities resulting in poor gas exchange, and capillary mechanics. This proposal utilizes the novel technology of diffuse light scattering (DLS), wherein changes in pulmonary surface to volume ratio, capillary blood volume, and capillary oxygenation can be assessed. DLS is unique insofar as it can be applied in vivo and in unfixed excised preparations; it is a "window" on pulmonary mechanics and gas exchange heretofore unavailable for studies in both health and disease.