PULMONARY MICROCIRCULATORY HEMODYNAMICS

肺循环是一个简单的血管床：低阻力，高阻力， 流动，主要是被动电路，然而，能够平衡 通过缺氧性血管收缩将灌注转换为通气。 相对于 然而，实际气体交换血管的血流动力学存在许多问题， 未开发的领域以及争议领域。 在本提案中，我们 将研究气体灌注的基本方式， 通过直接研究肺血管的变化， 微循环使用在体内视频显微镜，一种方法，我们有 在过去的三十年里发展起来的。 根据试点数据， 每个概念，我们将测试以下工作假设的各个方面： (1)个体肺泡内毛细血管之间的恒定流量转换 墙壁是由主动和被动组件造成的，（2）“非肌肉” 毛细血管前小动脉和毛细血管后小静脉能够 收缩，（3）小肌肉动脉阻抗由 交感神经刺激 我们开发了新方法来测试 这些想法包括毛细血管统计分析软件， 灌注模式，图像增强系统，用于精确测量 微血管直径，高输出激光光源，和非- 红细胞的创伤性荧光标记。 利用这些 技术，我们将探讨我们的发现，灌注模式的 肺毛细血管在单个肺泡壁内恒定流动， 即使当上游血管压力和流量保持恒定时。 实验旨在研究毛细血管灌注是否 模式改变是由收缩调节的，或者是被动的， 微粒流体穿过极其复杂的毛细管 网络 我们将调查长期模式波动是否 都是分形的 进一步的研究将确定在多大程度上 不同的灌注模式是白细胞 暂时滞留在肺毛细血管中 我们的试点研究还 证明了单个腺泡的灌注是相当重要的， 异质性表明通气-灌注平衡可能 是腺泡所必需的 因此，小动脉和小静脉， 可能在通气-灌注平衡中起积极作用。 我们确实 初步研究显示毛细血管前小动脉和毛细血管后小动脉 小静脉能够收缩血管，这表明 在腺泡功能区内微调流量调节的可能性 肺的单位。 最后，我们将研究交感神经的作用 刺激肌性肺动脉并记录结果 气体交换血管灌注的改变。 任何明显 血流改变可能是生理学意义上的， 部分神经系统对肺灌注的影响至今仍是个谜。 我们认为这些对肺微循环的研究 提供了一个独特的机会， 调节气体交换容器的灌注。

The pulmonary circulation is a simple vascular bed: a low resistance, high flow, largely passive circuit which, nevertheless, is capable of balancing perfusion to ventilation by hypoxic vasoconstriction. With regard to the hemodynamics of the actual gas exchange vessels, however, there are many unexplored areas as well as areas of controversy. In this proposal, we will investigate the fundamental ways in which perfusion of the gas exchange vessels is regulated by directly studying the pulmonary microcirculation using in vivo video microscopy, a method we have developed during the last three decades. Based on pilot data supporting each concept, we will test aspects of the following working hypotheses: (1) the constant flow switching between capillaries in individual alveolar walls is caused by both active and passive components, (2) "non-muscular" precapillary arterioles and post-capillary venules are capable of constriction, (3) small muscular arterial impedance is regulated by sympathetic nerve stimulation. We have developed new methods to test these ideas including software for statistical analysis of capillary perfusion patterns, an image enhancing system for accurate measurement of microvascular diameters, a high-output laser light source, and the non- traumatic fluorescent labeling of red blood cells. Utilizing these techniques, we will explore our finding that the perfusion pattern of the pulmonary capillaries is in constant flux within a single alveolar wall, even when upstream vascular pressures and flows are held constant. Experiments are designed to investigate whether the capillary perfusion pattern alterations are regulated by constriction or are the passive result of a particulate fluid crossing an extremely complex capillary network. We will investigate whether the long-term pattern fluctuations are fractal in nature. Additional studies will determine to what extent the variable perfusion pattern is the result of leukocytes being transiently trapped in the pulmonary capillaries. Our pilot studies also demonstrate that the perfusion of a single acinus is considerably heterogeneous suggesting that ventilation-perfusion balance may be necessary within an acinus. Small arterioles and venules, therefore, might have an active role in ventilation-perfusion balance. Indeed our preliminary work shows both precapillary arterioles and post-capillary venules to be capable of vasoconstriction, suggesting the unsuspected possibility of finely-tuned flow regulation within the acinar functional unit of the lung. Finally, we will study the effects of sympathetic nerve stimulation on muscular pulmonary arteries and record the resultant alterations in perfusion of the gas exchange vessels. Any demonstrable flow alterations could be of physiologic import, for the function of this part of the nervous system on pulmonary perfusion has remained enigmatic. We believe these proposed investigations of the pulmonary microcirculation offer a unique opportunity for exploring the fundamental ways in which perfusion of the gas exchange vessels is regulated.