DYNAMICS OF FLOW-DEPENDENT ARTERIAL PERMEABILITY

本研究的总体目标是了解这些因素 影响动脉壁对大分子的摄取，和 特别是通过局部血液动力学调节这种摄取。 的 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 动脉介导 通过血液动力学因素的摄取是特别感兴趣的，因为 动脉粥样硬化病变的分布表明， 可能参与疾病的定位;此外， 血液动力学应力可影响局部动脉 磁导率 这项研究的一个主要假设是， 跨内皮流量的一部分发生在增加， 响应于流动变化而发生的渗透性;因此， 特别强调的是放在动态响应的障碍 血管壁对血液动力学环境变化的功能。 研究目标是通过一个独特的组合， 动物实验和体外流动模拟。 在一系列基线中， 实验中，白蛋白的空间变化，渗透性， 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物获得。 一种新型 将在猪体内植入遥测装置以获得相位流数据 在这些部分。 壁面剪切速率在不同区域的分布 将从激光多普勒风速仪中获得顺应流兴趣- 通过血管的复制品，从腹腔口延伸到 股动脉;遥测数据将用于规定 实验流波 血流动力学应激与 将评估这些正常动物的白蛋白摄取。 基线研究中采用的技术将用于 定义改变的渗透性引起的变化的时间过程 流 流量变化将通过狭窄或狭窄的实验产生， 可逆性动静脉分流 渗透率与 响应（例如，振幅，时间常数），以及局部壁面剪力和 将检查剪切力的变化。 高胆固醇血症对 血管渗透性及其对流量变化的动态响应将是 也检查了。

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.