ALVEOLAR SURFACE FORCES EFFECTS ON LUNG FUNCTION

描述(改编自申请人的摘要)：本提案重点 关于组织力和表面力的相互作用 肺内的气液界面，以及这些界面如何决定 导致人体功能正常或功能障碍的微结构环境 实质力学、气体交换、肺毛细血管力学和 表面活性物质替代疗法。这些问题在以下方面尤为重要 建立病理生理基础的基本机制 新生儿和成人呼吸窘迫的差异及其原因 差异导致表面活性物质替代的效果截然不同 心理治疗。肺毛细血管顺应性对血流很重要 在肺中的分布，并与转运和隔离有关 白血球，炎症的一种普遍成分。实验将是 在麻醉绵羊和具有表面张力的离体肺中完成 生理盐水冲洗引起的改变，用恒定的表面张力冲洗 油，以及体内的油酸给药。结果将确立 急性肺损伤的影响方式：肺泡和肺的几何形态 肺泡管，实质稳定性，区域不均匀导致 气体交换差，以及毛细管力学。这项建议利用了 漫反射光散射(DLS)新技术 肺表面体积比、毛细血管血容量和毛细血管 氧合作用可以被评估。DLS的独特之处在于它可以应用于 在体内和未固定的切除制剂中；它是肺 力学和气体交换到目前为止还不能用于这两个健康领域的研究 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.