CORONARY MICROVESSEL PERMEABILITY

在心脏内部，运动训练增加了冠状动脉的渗透性- 表面积产品，交换容量的指数，由未知 机制等目前对毛细交换屏障的看法是， 从一个静态的边界发展到一个动态的结构 在气体、水和溶质运动的瞬间调节中， 血液和组织的区别 由于表面积不占 观察到培训引起的交换容量增加，该项目 专注于微血管渗透性，并应用专门的 该实验室的技术来测量微血管运输。 从 这些测量结果表明了冠状动脉微血管 将阐明对运动训练的适应。 主 假设运动训练增加了冠状动脉微血管 渗透性（目标1和2）。 此外，这些研究旨在 确定培训效果是局部的还是系统的（目标3）， 运动训练改变了血管屏障的动态状态（目的 4），和/或个体血管的变化是否同样有助于 完整心脏的综合反应（目的5）。 电阻 从心脏和肠系膜分离的动脉和小静脉 ad运动训练的猪，已知大小的荧光探针的溶质通量 和变化将作为灌注压的函数来测量。 从 这些测量的传输系数扩散溶质 渗透率（Pd）和溶剂阻力系数（Lp（1-σ））将是 计算了 将评估微血管的渗透性反应 在基础条件下，然后用内皮细胞灌注- 依赖性和非依赖性血管扩张剂。 渗透率/表面积 产品也将被测量，首先，在整个心脏从久坐不动， 运动训练的猪，第二，在阻力动脉和小静脉 从这些相同的心脏中分离出来。 了解决定 控制单个微血管和完整心脏中的渗透性将 为阐明观察到的运动训练诱导的 增加冠状动脉交换能力。 理解的关键 运动训练是否能补偿或逆转 也依赖于一种机械的方法来研究 通过训练观察到的变化。

Within the heart, exercise training increases coronary permeability- surface area product, an index of exchange capacity, by unknown mechanisms. The current view of the capillary exchange barrier has progressed from one of a static boundary to a dynamic structure involved in moment-to-moment regulation of gas, water, and solute movements between blood and tissue. Since surface area does not account for the observed training-induced increase of exchange capacity, this project focuses on microvessel permeability and applies the specialized techniques of this laboratory to measure microvessel transport. From these measurements the mechanisms responsible for coronary microvessel adaptation to exercise training will be elucidated. The primary hypothesis is that exercise training increases coronary microvessel permeability (Aims 1 & 2). Further, the studies are designed to determine whether training effects are local or systemic (Aim 3), whether exercise training alters the dynamic status of the vascular barrier (Aim 4), and/or whether changes in individual vessels contribute equally to the integrated responses of intact hearts (Aims 5). In resistance arteries and venules isolated from the heart and mesentery of sedentary ad exercise trained pigs, solute flux of fluorescent probes of known size and change, will be measured as a function of perfusion pressure. From these measurements the transport coefficients diffusive solute permeability (Pd) and solvent drag coefficient (Lp(1-sigma)) will be calculated. Permeability responses of the microvessels will be assessed under basal conditions and then following perfusion with endothelium- dependent and -independent vasodilators. Permeability/surface area product will also be measured, first, in whole hearts from sedentary and exercise trained pigs and, second, in resistance arteries and venules isolated from these same hearts. Knowledge of mechanisms that dictate control of permeability in individual microvessels and intact hearts will provide a basis for elucidating observed exercise training-induced increases in coronary exchange capacity. The key to understanding whether exercise training compensates for or reverses dysfunction caused by coronary disease also rests on a mechanistic approach to studying changes observed with training.