CORONARY VASCULAR PERMEABILITY & ENDOTHELIAL DYSFUNCTION

营养物质向组织的输送依赖于血液的流动和扩散 将营养物质从血管间隙输送到间质。而当 大量先前的研究已经检验了调节心肌细胞的因素 血流灌注方面，关于血管的研究相对较少 冠状动脉血管床的通透性。此外，最近它还 显而易见，内皮细胞对血管张力的调节可能是 在几种常见疾病状态下出现异常。是不是另一个 血管内皮的重要功能，调节血管通透性， 在这些疾病状态下是否也不正常尚不清楚。 我已经开发了一种技术，可以自由地检查完好无损的 心跳加速。在该奖项的五年期间，这项技术 将被用来研究冠状动脉的通透性 血管内皮细胞功能障碍的几种不同状态。这些 条件包括缺血和随后的再灌注，压力诱导 左心室肥厚、冠状动脉粥样硬化和冠状动脉 依赖成熟络脉的血管床。这其中的每一个 各种情况与血管内皮细胞异常调节有关 血管平滑肌张力。这些研究，除了允许我 为了开发新的研究技术，将调查 内皮调节冠脉血管通透性(因此 心肌营养素输送)，以及冠脉通透性如何变化 当内皮细胞功能失调时。

Delivery of nutrients to tissues is dependent upon blood flow and diffusion of nutrients from the vascular space to the interstitium. While substantial previous research has examined factors that regulate myocardial perfusion, there has been relatively little investigation of vascular permeability of the coronary vascular bed. Furthermore, it has recently become apparent that endothelial regulation of vascular tone may be abnormal in several commonly encountered disease states. Whether another important function of the endothelium, regulation of vascular permeability, is also abnormal in these disease states is not known. I have developed a technique for examining permeability of intact, freely beating hearts. During the five year period of this award, this technique will be employed to investigate the permeability of the coronary vasculature in several different states of endothelial dysfunction. These conditions include ischemia with subsequent reperfusion, pressure induced left ventricular hypertrophy, coronary atherosclerosis, and coronary vascular beds which are dependent upon mature collaterals. Each of these conditions have been associated with abnormal endothelial modulation of vascular smooth muscle tone. These studies, in addition to permitting me to develop new research techniques, will investigate the role of the endothelium in regulating coronary vascular permeability (and hence myocardial nutrient delivery), as well as how coronary permeability changes when the endothelium becomes dysfunctional.