CORONARY COLLATERAL FUNCTION

长期目标是阐明冠状动脉粥样硬化的机制， 侧支的生长和功能，并更好地描述反馈 控制清醒动物的冠状动脉血流。具体目标 （1）为了验证缺血不需要缺血的假设， 增加电导或逆转新开发的 侧枝。(2)为了在改进的动物模型中测试以下假设， 另一些人认为，通过侧支的慢性灌注产生内皮细胞， 受体血管功能障碍，（3）评估 冠状动脉和侧支血管内皮源性一氧化氮（EDNO） 血流调节，和（4）表征乙酰肝素的表达 在侧枝生长期间硫酸化蛋白聚糖。小马将被雇用 因为马科动物和人类在冠状动脉解剖学上有相似之处。 研究将在清醒动物中长期进行 （1）气动袖带封堵器，用于刺激 通过间歇性冠状动脉闭塞法进行侧支生长。（二） 多普勒流量探头、声测微晶体和微压计， 测量冠状动脉血流速度、心肌壁功能，以及 左心室压力，和（3）左心房中的导管，左 用于注射微球的冠状动脉和冠状前静脉， 研究心肌代谢，测量冠状动脉压力， 给冠状循环注射药物。该动物模型 提供了一种方法，用于创建连续或不连续的 血行新络，研究 非侵入性的侧支回退。涉及各种模式的协议 连续和间断侧支灌注，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，逐步减少冠状动脉 动脉压和心肌组织的分子生物学研究 将被雇用。 这项研究可以提供以下方面的新信息：（1） 血流依赖性机制在冠状动脉侧支生长中的作用， EDNO在反馈控制中的生理重要性 冠状动脉血流和反应性充血，和（3）分子 调节抵押品的增长。最终，这项研究可能会导致 减少术前和术后血管内膜下缺血的新策略 心肌梗塞冠心病。它还可以提供更好的 了解运动作为冠心病风险的生理基础 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.