PULMONARY MICROCIRCULATORY HEMODYNAMICS

肺循环是一个简单的血管床：低阻力，高阻力 流量，很大程度上是无源电路，但能够平衡 通过低氧血管收缩由灌流到通气机。关于 然而，实际的气体交换血管的血液动力学有很多 未开发的领域以及有争议的领域。在这项提案中，我们 将研究气体灌流的基本方式 交换血管通过直接研究肺组织来调节 微循环使用活体视频显微镜，我们有一种方法 在过去的三十年里发展起来的。基于试点数据支持 在每个概念中，我们将测试以下工作假设的各个方面： (1)单个肺泡毛细血管之间的恒流转换 墙既有主动成分也有被动成分，(2)“非肌肉性” 毛细血管前小动脉和毛细血管后小静脉能够 收缩，(3)小肌肉动脉阻抗受 交感神经刺激。我们已经开发了新的方法来测试 这些想法包括毛细管统计分析软件 血流灌注模式，一种图像增强系统，用于准确测量 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，我们将探索我们的发现，血流灌注模式 肺毛细血管在单个肺泡壁内恒定流动， 即使上游血管压力和流量保持不变。 实验旨在调查毛细血管灌流是否 模式转换是由收缩来调节的，或者是被动的 微粒流体穿过极其复杂的毛细管的结果 网络。我们将调查长期模式的波动是否 在本质上是分形的。其他研究将确定在多大程度上 不同的灌流模式是由于白细胞 暂时滞留在肺毛细血管内。我们的初步研究也 表明单个腺泡的灌注量相当大 异质性提示呼吸-灌流平衡可能是 在腺泡内是必需的。因此，小动脉和小静脉， 可能在通气性-灌注性平衡中起积极作用。事实上，我们的 初步工作显示毛细血管前小动脉和毛细血管后小动脉 小静脉有收缩血管的能力，这表明 腺泡功能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。 对肌性肺动脉的刺激并记录其结果 气体交换血管的灌注改变。任何明显的证据 血流改变可能具有生理意义，因为这一功能 神经系统的一部分对肺血流的影响一直是个谜。 我们相信这些关于肺微循环的研究建议 提供了一个独特的机会，探索以下基本方式 调节气体交换容器的灌流。

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.