DYNAMICS OF FLOW-DEPENDENT ARTERIAL PERMEABILITY

血流相关的动脉渗透性的动力学

• 批准号: 2226643
• 负责人: MORTON H FRIEDMAN
• 金额: $ 24.92万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226643
• 关键词: albumins; aorta; artery; atherosclerosis; atherosclerotic plaque; biological transport; hemodynamics; hypercholesterolemia; macromolecule; miniature swine; telemetry; vascular endothelium permeability

The overall objective of this research is to understand the factors affecting the uptake of macromolecules by the arterial wall, and particularly the mediation of this uptake by local hemodynamics. The interest in macromolecular transport is prompted by its importance in the genesis and development of atherosclerosis. The mediation of arterial uptake by hemodynamic factors is of particular interest because the distribution of atherosclerotic lesions suggests that hemodynamic factors may be involved in the localization of the disease; furthermore, there is evidence that hemodynamic stresses can influence local arterial permeability. A primary hypothesis of this research is that an important fraction of the transendothelial flux occurs during increases in permeability that occur in response to changes in flow; accordingly, particular emphasis is placed on the dynamic response of the barrier function of the vessel wall to changes in the hemodynamic environment. The research objectives are addressed through a unique combination of animal experiments and in vitro flow simulations. In a series of baseline experiments, the spatial variation of albumin, permeability in the terminal aorta and iliac-femoral arteries of normally behaving minipigs will be obtained, using Evans Blue dye as the primary marker. A novel telemetry device will be implanted in the pigs to obtain phasic flow data in these segments. The distribution of wall shear rates in the regions of interest will be obtained from laser Doppler anemometry in compliant flow- through replicas of the vessels, extending from the celiac orifice into the femoral arteries; the telemetry data will be used to prescribe the experimental flow wave. The relation between hemodynamic stress and albumin uptake in these normal animals will be assessed. The techniques employed in the baseline studies will next be used to define the time course of the change in permeability Induced by altered flow. The flow changes will be produced experimentally by stenoses or reversible arteriovenous shunts. The relation between the permeability response (e.g., amplitude, time constants), and the local wall shear and change in shear, will be examined. The effects of hypercholesterolemia on vascular permeability and its dynamic response to changes in flow will be examined as well.

本研究的总体目标是了解影响因素 影响动脉壁对大分子的摄取，以及 特别是局部血流动力学对这种吸收的调节。 这 人们对大分子运输的兴趣是由于它在运输中的重要性 动脉粥样硬化的发生和发展。 动脉的中介作用 血流动力学因素的摄取特别令人感兴趣，因为 动脉粥样硬化病变的分布表明血流动力学因素 可能参与疾病的定位；此外，还有 有证据表明血流动力学压力可以影响局部动脉 渗透性。 这项研究的一个主要假设是，一个重要的 跨内皮通量的一部分发生在 随流量变化而发生的渗透率；因此， 特别强调屏障的动态响应 血管壁的功能对血流动力学环境变化的影响。 研究目标是通过独特的组合来实现的 动物实验和体外流动模拟。 在一系列基线中 实验，白蛋白的空间变化，通透性 正常行为小型猪的终末主动脉和髂股动脉 将使用伊文思蓝染料作为主要标记来获得。 一本小说 遥测装置将被植入猪体内以获得相流数据 在这些细分市场中。 壁面剪切率在以下区域的分布 兴趣将从激光多普勒风速仪中获得顺应流- 通过血管的复制品，从腹腔孔延伸到 股动脉；遥测数据将用于规定 实验流波。 血流动力学应激与血流动力学压力之间的关系 将评估这些正常动物的白蛋白摄取情况。 基线研究中采用的技术接下来将用于 定义由改变引起的渗透率变化的时间过程 流动。 流量变化将通过狭窄或 可逆性动静脉分流术。 渗透率之间的关系 响应（例如振幅、时间常数）以及局部壁剪切和 将检查剪切力的变化。 高胆固醇血症对身体的影响 血管通透性及其对流量变化的动态响应将是 也进行了检查。