Pulmonary Microcirculatory Hemodynamics

描述（由申请人提供）：新的证据表明，在动脉和毛细血管中，肺循环具有意想不到的调节形式。我们实验室的肺微血管视频显微镜显示，并非所有的毛细血管都持续灌注；相反，血流在毛细血管之间不断地转换。即使在血管压力和流量恒定的情况下，这种转换也会继续。这种转换不是随机的：它遵循一种微妙的、重复的模式，这种模式在本质上是分形的，取决于每个肺泡网络的独特特征。这导致相邻肺泡之间的灌注模式是独立的，从而形成一个强大的系统，其中一个网络的故障不会影响到相邻的肺泡。具体目标确定导致单个毛细血管网络中毛细血管间流动转换的机制。这种切换可能是微粒流体流经复杂但被动的毛细血管网络的结果，也可能是由主动毛细血管舒缩引起的。为了区分这些原因，我们将使用我们开发的软件分析灌注模式，以及分形数学来确定灌注模式的重复程度。我们的第一个假设是毛细血管是被动的；血液在毛细血管之间流动的转换是高度灵活的红细胞穿过构成网络的数十个毛细血管连接处的结果。第二个假设是毛细血管是活跃的；血流在毛细血管间的转换是由毛细血管腔径的主动变化决定的。我们将通过创造一个被动状态来测试这些假设，在被动状态下，毛细血管的管腔直径是固定的，从而阻止毛细血管改变其管腔的能力。不变的交换表明网络是被动的。改变开关将是毛细血管舒缩的直接证据。在专项目标2中，我们将研究支配肺动脉的交感神经的功能。刺激星状交感神经节使肺动脉壁变硬，从而增加肺动脉收缩压。我们假设当增强的收缩压波到达毛细血管床时，气体交换表面积会通过毛细血管的聚集而增加。我们的试验数据有力地表明这个假设是正确的。我们将通过研究交感刺激时毛细血管灌注的变化来完成对这一假设的广泛检验。这些实验的成功完成将取代目前认为肺循环作用不大的观点，取而代之的是一种新的观点，即这些血管具有强大而微妙的控制能力。经过几十年的技术发展，我们终于有条件进行这些实验。

DESCRIPTION (provided by applicant): New evidence suggests that the pulmonary circulation has unexpected forms of regulation, both in the arteries and within capillaries. Videomicroscopy of the pulmonary microvasculature in our laboratory shows that not all capillaries are continually perfused; rather the blood flow continually switches among the capillaries. The switching continues even when vascular pressures and flows are constant. The switching is not random: it follows a subtle, repeating pattern that is fractal in nature and depends on the unique characteristics of each alveolar network. This results in perfusion patterns that are independent among neighboring alveoli, creating a robust system in which failure of one network does not affect the neighbors. Specific Aim 1. To determine the mechanisms that cause the switching of flow among capillaries in individual capillary networks. The switching could be the result of a particulate fluid flowing through a complex but passive capillary network, or it could be caused by active capillary vasomotion. To differentiate between these causes, we will analyze the perfusion patterns using software we have developed, as well as fractal mathematics to determine the level of repetition of the perfusion patterns. Our first hypothesis is that the capillaries are passive; the switching of blood flow among the capillaries is the result of highly flexible red blood cells traversing dozens of capillary junctions that comprise the network. The second hypothesis is that the capillaries are active; switching of blood flow among the capillaries is determined by active changes of capillary lumenal diameter. We will test these hypotheses by creating a passive state in which the capillary lumenal, diameters are fixed, thereby blocking the ability of the capillaries to alter their lumens. Unaltered switching would show that the network was passive. Altered switching would be direct evidence for capillary vasomotion. In Specific Aim 2 we will investigate the function of the sympathetic nerves that innervate the pulmonary arteries. Stimulation of the stellate sympathetic ganglion stiffens the pulmonary arterial walls, which increases pulmonary arterial systolic pressure. We hypothesize that when the enhanced systolic pressure wave reaches the capillary bed, the gas exchange surface area will increase through the recruitment of capillaries. Our pilot data strongly suggests this hypothesis is correct. We will complete an extensive test of this hypothesis by studying the changes in capillary perfusion during sympathetic stimulation. Successful completion of these experiments will replace the current idea, that the pulmonary circulation does not do very much, with a new concept that these vessels are capable of potent yet subtle control. After decades of technical development, we are at last in a position to conduct these experiments.