PULMONARY MICROCIRCULATORY HEMODYNAMICS

肺微循环血流动力学

• 批准号: 3350552
• 负责人: WILTZ WALKER WAGNER
• 金额: $ 17.48万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3350552
• 关键词: blood pressure; capillary bed; densitometry; dogs; dyes; erythrocytes; exercise; fluoresceins; fluorescence microscopy; hemodynamics; isolation perfusion; mathematical model; microcirculation; neural information processing; oxygen transport; pulmonary artery; pulmonary circulation; radiotracer; respiratory airway pressure; respiratory function; respiratory gas transport; vascular endothelium permeability; vascular resistance; videotape /videodisc

Only a small portion of available pulmonary gas exchange surface area is required to oxygenate blood completely during rest. However, when demands for oxygen become high, gas exchange capacity can be taxed. This challenge occurs in normal individuals during exercise or in diseased lungs at Test in which enough gas exchange units have been destroyed so that the flow load on the remaining normal units is very high. In both cases, the normally functioning gas exchange units must utilize all of their reserves to oxygenate blood effectively as flow increases. Understanding the mechanisms by which the normal pulmonary microcirculation responds to high flow, therefore, is physiologically important in both health and disease. Our working hypothesis is that there are three components of gas exchange reserve: (1) capillary recruitment which adds directly to surface area, (2) distension of capillaries which expands their cross sectional shape and permits more red cells to traverse the capillary bed per unit time, and (3) decreased capillary transit time which forces more red cells per unit time through the capillaries. Detailed information about these aspects of gas exchange reserve at the alveolar level are sparse, because of the technical difficulty in making direct measurements. During the last 25 years, we have developed the in vivo videomicroscopy techniques necessary for directly studying capillary recruitment, transit time, and distension. In this application we propose investigations of the mechanisms that control intra-alveolar capillary recruitment and transit times by applying our videomicroscopy technique not only to intact animals but also to an isolated, perfused lobe model in which flow and pressure are rigorously controlled and capillary pressures are measured exactly by the double occlusion technique. These preparations permit a wide range of novel experiments to investigate pulmonary capillary perfusion at the alveolar and capillary segmental level. Our first aim is to determine the factors that control pulmonary capillary recruitment in single alveolar walls by altering pressure and flow independently and observing the effect on: (a) the temporal stability of perfusion patterns, (b) the distribution of capillary segment opening pressures and resistances, and (c) the effects of microtheologic alterations by changing hematocrit, white blood cell count, and red cell deformability using fixed or sickled cells. Our second aim is to determine the interactive effects of vascular pressure and flow on the distribution f capillary transit times for red blood cells in single capillary nets. By independently altering pulmonary blood flow, transmural pressure, pressure waveform, and hematocrit, we can determine the effect of these variables on the distribution of transit times. These studies will provide important information on the transit of the fastest red cells, the ones most likely to leave the capillaries in a desaturated state during high flow, and on how recruitment and distension interact to keep transit times from becoming too short for complete red cell oxygenation.

只有一小部分可用肺气体交换 休息时需要表面积使血液完全充氧。 然而，当对氧气的需求变高时，气体交换能力可以 被征税。这一挑战发生在普通人的锻炼或 在检测到足够的气体交换单元的病变肺中 因此剩余的正常单元上的流量负荷非常大 很高。在这两种情况下，正常运行的气体交换装置必须 利用他们所有的储备来有效地为血液充氧 增加。了解正常肺组织的发病机制 因此，微循环对高流量的反应是生理上的。 对健康和疾病都很重要。我们的工作假设是 天然气交换储备库有三个组成部分：(1)毛细管 直接增加表面积的招募，(2)扩张 毛细血管，扩大其横截面形状，并允许更多 单位时间内红细胞穿过毛细血管床，(3)减少 毛细血管通过时间迫使更多的红细胞在单位时间内通过 毛细血管。关于气体的这些方面的详细信息 肺泡水平的外汇储备稀少，因为 直接测量的技术困难。在过去25年中 多年来，我们已经开发出了必要的活体视频显微镜技术 用于直接研究毛细管补充、渡越时间和 膨胀。在本申请中，我们建议调查 控制肺泡内毛细血管募集和转运的机制 将我们的视频显微镜技术不仅应用于完整的 动物，也是一个孤立的，灌流的叶模型，在其中流动和 严格控制压力，测量毛细管压力 完全是通过双遮挡技术。这些准备工作允许 广泛的新颖实验来研究肺毛细血管 肺泡和毛细血管节段水平的血流灌注。我们的首要目标是 是确定控制肺毛细血管复张的因素 在单个肺泡壁中，通过独立改变压力和流量 观察对以下方面的影响：(A)灌流的时间稳定性 (B)毛细管段开口压力的分布和 阻力，以及(C)微神学改变的影响 改变红细胞压积、白细胞计数和红细胞变形性 使用固定的或镰状的牢房。我们的第二个目标是确定 血管压力和流量对血流分布的交互影响 红细胞在单个毛细管网中的毛细血管通过时间。通过 独立改变肺血流量，跨壁压， 压力波形和红细胞压积，我们可以确定这些影响 关于运输时间分布的变量。这些研究将 提供有关最快的红血球转运的重要信息， 最有可能使毛细血管处于饱和状态的血管 在高流量期间，以及招聘和扩张如何相互作用以保持 转运时间不会变得太短，无法使红细胞完全充氧。