REGIONAL CONTROLLERS OF PULMONARY GAS EXCHANGE

肺通气量区域分布的对应关系 (VA)而灌注（Q）是肺有效功能的核心 无论是健康还是疾病。尽管有大量的工作致力于 研究肺内Q分布的局部控制， 当地VA的重要控制在很大程度上被忽视了。初步 使用PET的研究表明，局部VA的分布是 与Q紧密结合，可能是一个更有效， 比以前认识到的重要机制。 该项目的主要目标是在动物模型中进行研究 （羊），被动和主动因素控制的机制， 正常和病理性非- 使用正电子发射断层扫描（PET）检查均匀的肺部。我们的目标 研究内容包括：1）评估被动机制的局部贡献， 例如重力和结构，以及主动控制器，例如支气管 和血管平滑肌在确定VA的局部分布中的作用， 正常肺的VA /Q。2)为了表征时间依赖性， 这些机制运作的长度尺度。（三）阐明 VA和Q的局部控制优化气体交换的机制 肺，特别是体循环和支气管循环的作用 博士 新的PET成像方法将被用于非侵入性地测量 局部气体交换相关变量与现代图像技术 处理将被应用于表征空间异质性的 衍生功能图像。我们的PET成像方法的独特功能 同时评估Q和VA和质量传输现象， 邻近血气界面的远端气隙将提供 到目前为止仍然难以捉摸的基本生理现象。 除了从中获得有价值的生理信息外， 项目，其结果将有直接的临床应用，如在 高原肺栓塞低氧血症的处理 水肿最后，该项目将产生实验和分析工具 这将是理解，开发和测试新的 优化气体交换的方法，如吸入NO和液体通气。

The correspondence between regional distribution of pulmonary ventilation (VA) and perfusion (Q) is central to the efficient function of the lungs in both health and disease. In spite of a vast amount of work devoted to studying the local control of intrapulmonary Q distribution, the equally important control of local VA has been largely overlooked. Preliminary studies using PET have suggested that the distribution of local VA is intimately coupled to that of Q and could be a far more effective and important mechanism than previously appreciated. The primary objective of this project is to study, in an animal model (sheep), the mechanisms by which passive and active factors control the topographic distribution of gas exchange in normal and pathologically non- uniform lungs using positron emission tomography (PET). The aims of our research are: 1) to assess the local contributions of passive mechanisms, such as gravity and structure, and, active controllers, such as bronchial and vascular smooth muscle in determining the local distributions of VA, Q, and VA /Q in normal lungs. 2) To characterize the time dependence and length scale at which these mechanisms operate. And 3) to elucidate the mechanisms by which local control of VA and Q optimize gas exchange in the lung and specifically, the role of the systemic and bronchial circulation pH. Novel PET imaging methods will be used to measure non-invasively the relevant variables of local gas exchange and modern techniques of image processing will be applied to characterize the spatial heterogeneity of the derived functional images. The unique features of our PET imaging method to assess simultaneously Q and VA and the mass transport phenomena in distal airspaces adjacent to the blood gas interface will give insights into basic physiological phenomena that until now have remained elusive. Aside from the valuable physiological information to be derived from this project, the results will have direct clinical applications such as in the management of hypoxemia during pulmonary embolism high altitude pulmonary edema. Finally, this project will yield experimental and analytical tools that will be crucial for understanding, developing and testing of novel methods to optimize gas exchange such as inhaled NO and liquid ventilation.