LOCAL REGULATION OF MICROVASCULAR FUNCTION

微血管功能的局部调节

• 批准号: 2214692
• 负责人: BRIAN R DULING
• 金额: $ 29.66万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2214692
• 关键词: adenosine; arachidonate; arterioles; body fluid osmolarity; cell type; cytochrome P450; diabetic angiopathy; erythrocytes; fatty acid metabolism; hamsters; hypertension; microcirculation; oxygen transport; peripheral blood vessel; reactive hyperemia; sickle cell crisis; striated muscles; vascular resistance

The ultimate goal of this work is to understand the limits to and control of tissue oxygenation. Current views of the local control process are inadequate to account for certain integrative phenomena and for the capillary oxygen content. We will explore this problem in two lines of experimental investigation. First, structure- function relations in small arteries, arterioles and capillaries will be assessed in relation to regulation of total blood flow, heterogeneity of blood flow and intracapillary oxygen content. These experiments will be executed using techniques including: three dimensional reconstruction of the patterns of fluorescent red cells, in situ microvessel perfusion with artificial blood, and servo-null measurement of intravascular pressure, 3-dimensional reconstructions of the red cell flow patterns will be used in the formulation of a modular mathematical model of the red cell flow distribution in the microvascular tree. The importance of endothelial cell surface structures as determinants of capillary tube hematocrit will be determined using selective enzymatic attack on the endothelial cell surface glycoproteins. This work will be complemented by thin and thick section electron microscopy and 3- dimensional reconstructions of the vessel wall. The second line of investigation will employ microperfusion and microiontophoresis to induce and study propagated and flow-dependent vasomotor responses. These data will be employed in a description of the nature of longitudinal communication along the vascular axis. We will utilize selective damage and intracellular marking with lucifer yellow to ascertain the cell types responsible for the propagated responses. Enzymatic treatment will be used to explore the cellular basis for flow-dependent vasodilation. The experimental findings should provide a quantitative definition of the factors that limit tissue oxygenation. In addition, fundamental new information should be derived concerning the rules for longitudinal integration of vascular function.

这项工作的最终目标是了解和 控制组织氧合。 本地控制的当前视图 过程不足以说明某些综合现象 以及毛细血管氧含量。 我们将探索这个问题 在两行实验研究中。 首先，结构 - 小动脉，小动脉和毛细血管的功能关系 将根据总血流调节进行评估， 血流和毛细血管内氧含量的异质性。 这些实验将使用：包括： 荧光模式的三维重建 红细胞，原位微血管灌注，用人造血液灌注，并且 血管内压，3维的伺服无效测量 红细胞流量模式的重建将在 红细胞流的模块化数学模型的公式 微血管树中的分布。 重要性 内皮细胞表面结构作为毛细管的决定因素 管血细胞比容将使用选择性酶促攻击确定 在内皮细胞表面糖蛋白上。 这项工作将是 与薄截面电子显微镜和3-相辅相成 容器壁的尺寸重建。 第二行 调查将采用微灌注和微孔液压 诱导和研究繁殖和流动依赖性血管舒缩剂 回答。 这些数据将用于描述 沿血管轴纵向通信的性质。 我们 是否会使用选择性损害和细胞内标记 Lucifer黄色以确定负责的细胞类型 传播的响应。 酶促处理将用于探索 流量依赖性血管舒张的细胞基础。 这 实验发现应提供定量定义 限制组织氧合的因素。 此外， 基本的新信息应获得有关规则的 用于血管功能的纵向整合。