CORONARY COLLATERAL FUNCTION

长期目标是阐明冠心病的发病机制。 附带增长和功能，并更好地描述反馈 清醒动物冠脉血流的控制。具体目标 是：(1)检验不需要缺血的假设 新开发的电导增加或逆转回归 抵押品。(2)在改进的动物模型中检验假说 其他人则认为通过络脉的慢性灌流会产生内皮细胞 受者血管系统功能障碍，(3)评估其重要性 冠状动脉及侧支循环中内皮源性一氧化氮(EDNO)的变化 血流调节，以及(4)表征肝素的表达 侧枝生长期间的硫酸盐蛋白多糖。小马将被雇佣 因为马科动物和人类在冠状解剖上有相似之处。 这些研究将在有意识的动物身上长期进行 配备有：(1)用于刺激的气动袖口封闭器 间歇性冠脉闭塞法的侧枝生长。(2) 多普勒流探头、声波测微仪晶体和显微压力计 测量冠脉血流速度、心肌壁功能和 左心室压力；(3)左心房导管，左 冠状动脉和冠状动脉前静脉注射微球， 研究心肌代谢，测量冠状动脉压力，以及 将物质注入冠状循环。这个动物模型 提供了一种创建连续或不连续期间的方法 血液流经新发展的络脉及其研究 非侵入性的侧支回归。涉及各种模式的协议 连续和不连续侧支循环灌流，异丙肾上腺素 压力测试，冠状动脉内给药，包括 环氧合酶和EDNO抑制剂在冠状动脉病变中的逐步减少 动脉压与心肌组织的分子生物学研究 将会被雇佣。这项研究可以为以下方面提供新的信息 血流依赖机制在冠脉侧支生长和冠状动脉病变中的作用 功能，(2)EDNO在反馈控制中的生理重要性 冠脉血流和反应性充血，以及(3)分子 对抵押品增长的监管。最终，这项研究可能会导致 减少心内膜下缺血治疗前后的新策略 心梗、冠心病。它还可以提供更好的 了解运动作为冠状动脉风险的生理学基础 折减系数。

The long term objectives are to elucidate mechanisms of coronary collateral growth and function, and to better characterize feedback control of coronary blood flow in the conscious animal. The specific aims are: (1) to test the hypothesis that ischemia is not required for increasing conductance or reversing regression of newly developed collaterals. (2) to test in an improved animal model the hypothesis of others that chronic perfusion through collaterals produces endothelial dysfunction in the recipient vasculature, (3) to evaluate the importance of endothelial derived nitric oxide (EDNO) in coronary and collateral blood flow regulation, and (4) to characterize the expression of heparan sulfate proteoglycans during collateral growth. Ponies will be employed because of similarities between equidae and humans in coronary anatomy. The studies will be performed in conscious animals chronically instrumented with: (1) a pneumatic cuff occluder for stimulating collateral growth by an intermittent coronary occlusion method. (2) Doppler flow probe, sonomicrometry crystals, and micromanometer for measuring coronary blood flow velocity, myocardial wall function, and left ventricular pressure, and (3) catheters in the left atrium, left coronary artery, and anterior coronary vein for injecting microspheres, studying myocardial metabolism, measuring coronary artery pressure, and administering substances into the coronary circulation. This animal model provides a means for creating periods of continuous or discontinuous blood flow through newly developed collaterals and for studying collateral regression non-invasively. Protocols involving various modes of continuous and discontinuous collateral perfusion, isoproterenol stress testing, intracoronary administration of drugs, including cyclooxygenase and EDNO inhibitors, stepwise reductions in coronary artery pressure and molecular biological studies on myocardial tissues will be employed. This research could provide new information on (1) the role of flow-dependent mechanisms in coronary collateral growth and function, (2) the physiological importance of EDNO in feedback control of coronary blood flow and reactive hyperemia, and (3) molecular regulation of collateral growth. Ultimately, this research could lead to new strategies for reducing subendocardial ischemia in pre-and post infarction coronary heart disease. It could also provide a better understanding of the physiological basis for exercise as a coronary risk reduction factor.