NON-G DETERMINANTS OF PULMONARY PERFUSION HETEROGENEITY

描述（申请人摘要）：肺循环通常是 被认为是一个很大程度上被动的回路，其中血流分布 很大程度上取决于重力引起的流体静力学梯度- a 这一观点主导了对《圣经》的解释和指导， 在过去的三十年里，与肺灌注相关的研究。 然而，在这方面， 最近的研究使用高分辨率和实验进行， 微重力表明肺灌注的不均匀性要大得多 比仅用重力所能解释的还要多。 在本提案中，我们将建立在 我们对灌注异质性的理解来阐明机制， 除了重力之外，它决定了肺中的血流分布。 需要血流分布的高分辨率测量， 在一系列尺度上研究灌注异质性的机制 从主肺动脉到肺泡毛细血管 为此，委员会建议， 我们已经建立了探索空间分布的方法， 在微观水平上，肺血流贯穿整个肺。 我们的具体目标是：1）获得局部肺动脉的测量值， 大鼠、家兔、犬和雪貂肺泡毛细血管水平的灌注 并确定是否存在流动均匀的单元。 2)量化 毛细血管容积、肺泡容积和 血管运动，并确定其对灌注异质性的贡献。 第三章 为了确定缺氧性肺血管收缩是否引起均匀或 急性和慢性全球性心脏病期间血流不均匀再分布 缺氧 4)为了确定肺灌注的新概念是否 通过研究肺组织的分布， 狒狒的血液流动 空间分析的统计方法 微球的分布将被用来表征区域 灌注分布 这些研究的一个不可或缺的结果将是 肺血流的新模型，调和以前的观察结果， 从这个项目中获得新的见解。 除了这些新的信息， 基本肺功能，肺灌注分布现在可以探索 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.