VASCULAR CELL INTERACTIONS AND FLOW IN VIVO

该项目的重点是终端微血管网络的作用， 确定血细胞（红细胞、RBC和 白细胞，WBC）和在确定血液流动分布中的作用。 微脉管系统我们认为血流和血细胞的异质性 行为是当地生物物理现象及其 生物学成果。一般目标1集中在RBC的决定因素 分布目的1.1检验红细胞分布到 通过毛细血管的流量是RBC表面与体积比的函数。 在项目3中，将确定改性RBC的流动特性， 毛细血管急性和慢性;细胞机械性能将是 在体外测量和RBC流量和速度和毛细血管几何形状， vivo.目的1.2检验分叉几何形状有助于 红细胞分布的不对称性，使用灌注的红细胞悬液 通过微通道系统模拟末端小动脉 分叉几何第二章探讨了 内皮细胞（EC）细胞骨架与流动的重新排列，以及几何形状 （曲率）的EC生长表面。目标2.1检验假设， 内皮细胞对流动的细胞骨架反应在生长于不同的细胞上是不同的， 曲面与平面相比。F-肌动蛋白分布将在 不同来源的内皮细胞在不同的流动和曲率下生长。焦 还将测量粘附分布。目标2.2检验假设 体内EC可以响应细胞骨架的流动变化， 重新调整局部灌注的小动脉将用于混合 微血管和染色F-肌动蛋白，在不同流量的血管活性物质， 刺激。目标3阐述了WBC-EC的基本机制 体内的相互作用。目的3.1检验了以下假设： 白细胞在小静脉中的分布是由于白细胞的优选流动通道。 WBC流量变量将与微静脉相关进行定量 结构，在不同的流量，或没有选定的粘附分子。 粘附分子的局部小静脉异质性将通过以下方式定量： P-选择素和ICAM-1的分布，并通过使用WBC停止 项目1开发的时间分析。目标3.2测试他们的假设， EC-WBC相互作用可由于EC中的流动相关变化而改变。 在项目2中，我们将测量体内EC体积变化和WBC流量 组织缺血前后，并用阿米洛利预防EC 变化在微通道中，我们将探索EC的潜在机制 体积对流量的反应，以及对WBC-EC相互作用的影响。

This project focuses on the role of the terminal microvascular network in determining the variable behavior of blood cells (erythrocytes, RBC and leukocytes, WBC) and in determining blood flow distributions in the microvasculature. We view the heterogeneity in blood flow and blood cell behavior as a predictable result of local biophysical phenomena and their biological outcomes. Gen. Aim 1 centers on determinants of RBC distribution. Aim 1.1 tests the hypothesis that RBC distribution into, and flow through, capillaries is a function of RBC surface to volume ration. With Project 3, flow properties of modified RBCs will be determined in capillaries both acute and chronically; cell mechanical properties will be measured in vitro and RBC flux and velocity and capillary geometry in vivo. Aim 1.2 tests the hypothesis that bifurcation geometry contributes to asymmetries in distribution of RBCs, using RBC suspensions perfused through microchannel systems constructed to mimic terminal arteriolar bifurcation geometry. Gen. Aim 2 explores the relationship between endothelial cell (EC) cytoskeletal realignment with flow, and the geometry (curvature) of the EC growth surface. Aim 2.1 tests the hypothesis that the cytoskeletal responses of ECs to flow is different in cells growing on curved compared to flat surfaces. F-actin distribution will be measured in ECs of different origins grown under varying flow and curvature. Focal adhesion distribution will also be measured. Aim 2.2 tests the hypothesis that ECs in vivo can respond to flow changes with cytoskeletal realignment. Local perfusion of arterioles will be used to mix microvessels and stain F-actin, under differing flow of vasoactive stimuli. Gen. Aim 3 addresses the mechanisms underlying WBC-EC interactions in vivo. Aim 3.1 tests the hypothesis that heterogeneity in WBC distribution among venules is due to preferred flow channels for WBCs. WBC flow variables will be quantitated in related to the venular architecture, at differing flows, or without selected adhesion molecules. Local venular heterogeneity in adhesion molecules will be quantitated from the distribution of P-selectin and ICAM-1, and also by using a WBC stopped time analysis developed by Project 1. Aim 3.2 tests they hypothesis that EC-WBC interactions can be changed due to flow related changes in ECs. With Project 2 we will measure EC volume changes and WBC flows in vivo before and after tissue ischemia, and with amiloride to prevent EC changes. In microchannels we will explore that mechanism underlying the EC volume response to flow, and effects on WBC-EC interactions.