NON-G DETERMINANTS OF PULMONARY PERFUSION HETEROGENEITY

说明(申请人摘要)：肺循环一般为 被认为是一个很大程度上被动的循环，其中的血流分布 很大程度上是由重力引起的静力梯度决定的 在解释和指导方面占据主导地位的观点 近三十年来与肺血流灌注相关的研究。然而， 最近使用高分辨率进行的研究和在 微重力显示肺血流灌注的异质性要大得多。 仅靠重力是无法解释的。在这项提案中，我们将在 我们对灌注异质性的理解，以阐明其机制， 而不是重力，它们决定了肺内的血流分布。 需要高分辨率的血流分布测量来 在一系列尺度上研究血流灌注异质性的机制 从主肺动脉到肺泡毛细血管。为此， 我们已经建立了探索空间分布所需的方法 肺血流在显微镜水平上遍及整个肺。 我们的具体目标是：1)获得区域肺功能的测量结果 大鼠、兔、狗和雪貂肺泡毛细血管水平的血流灌注 并确定是否存在流动均匀的单元。2)量化 毛细血管体积、肺泡体积和 血管运动，并确定其对血流灌注异质性的贡献。3) 为了确定缺氧性肺血管收缩是否导致均匀或 全球急慢性流量的非均匀再分布 缺氧。4)确定肺灌注的新概念是否 通过研究肺组织的分布，异质性适用于人类 蜻蜓体内的血液流动。空间分析的统计方法 微球的分布将被用来表征区域 血流灌注分布。这些研究的一个完整结果将是 肺血流的新模型，符合先前的观察和 从这个项目中获得新的见解。除了关于以下方面的新信息 现在可以探索基本肺功能、肺血流灌注分布 在小动物疾病模型中。

DESCRIPTION (Applicant's abstract): The pulmonary circulation is generally regarded as a largely passive circuit in which blood flow distribution is largely determined by the hydrostatic gradient due to gravity - a perspective that has dominated both the interpretation and direction of studies related to pulmonary perfusion for the last three decades. However, recent studies using high resolution and experiments performed in microgravity have shown that pulmonary perfusion is much more heterogeneous than can be explained by gravity alone. In this proposal we will build on our understanding of perfusion heterogeneity to elucidate the mechanisms, other than gravity, that determine blood flow distribution in the lung. High resolution measurements of blood flow distribution are needed to investigate mechanisms of perfusion heterogeneity over a range of scales from the main pulmonary arteries to the alveolar capillaries. To this end, we have established methods needed to explore the spatial distribution of pulmonary blood flow throughout the entire lung at the microscopic level. Our Specific Aims are: 1) To obtain measurements of regional pulmonary perfusion at the alveolar capillary level in rats rabbits, dogs, and ferrets and determine if there is a unit in which flow is uniform. 2) To quantify the regional variability in capillary volume, alveolar volume, and vasomotion and determine their contribution to perfusion heterogeneity. 3) To determine if hypoxic pulmonary vasoconstriction causes uniform or heterogeneous redistribution of flow during acute and chronic global hypoxia. 4) To determine whether the new concepts of pulmonary perfusion heterogeneity apply to humans by studying the distribution of pulmonary blood flow in baboons. Statistical methods for analyzing spatial distributions of microspheres will be used to characterize regional perfusion distribution. An integral outgrowth of these studies will be a new model for pulmonary blood flow, reconciling previous observations and new insights from this project. In addition to this new information on basic lung function, pulmonary perfusion distributions can now be explored in small-animal disease models.