CORONARY MICROVASCULAR RESPONSES TO HUMORAL SUBSTANCES

冠状动脉微血管对体液物质的反应

• 批准号: 3355598
• 负责人: KATHRYN G LAMPING
• 金额: $ 13.99万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355598
• 关键词: acetylcholine; adrenergic receptor; angiotensin II; collateral circulation; dogs; endothelin; heart circulation; heart contraction; heart pharmacology; microcirculation; serotonin; vagus nerve; vascular resistance; vasoactive agent; vasopressins

The objective of this proposal is to assess vasomotor responses of both native and mature collateral arteries and arterioles in vivo to neurohumoral and physiological stimuli by directly visualizing collateral microvessels on the left ventricle of the dog. Collateral microvessels on the epicardium will be visualized using two techniques. First, respiratory-induced motion is minimized using high frequency jet ventilation synchronized to the heart cycle. Second, motion of the heart due to contraction will be compensated for using computer-controlled stroboscopic epi-illumination synchronized to the cardiac cycle. Stroboscopic illumination visually freezes the motion of the heart enabling visualization of the microcirculation with a microscopic-video digitizing system. Thus, in an unrestrained heart vasomotor responses of microvessels from 30 to 400 micromoles can be measured. Microvascular pressures will be obtained using a computer-controlled electromechanical micropipette holder and the servo-null technique. Collaterals will be visually traced between the left anterior descending and left circumflex arteries using fluorescence angiography. Responses to both native and stimulated collaterals will be measured to test the hypothesis that the response of both native and stimulated collaterals to neurohumoral and physiological stimuli will be dependent upon the initial vessel size similar to non-collateral vessels. It is only with these techniques to visualize the coronary microcirculation that vasomotor responses of collaterals can be directly measured in vivo. The specific aims to be addressed in this proposal are: 1) to determine the response of both native and stimulated collaterals to vasodilators (nitroglycerin, acetylcholine) and vasoconstrictors (serotonin, endothelin, vasopressin and PGF2alpha.); 2) to determine the response of native collaterals to decreases in perfusion pressure and the vasodilator reserve with nitroglycerin or adenosine of collaterals in the presence of a flow-limiting stenosis or total occlusion; 3) to determine whether the response of native collaterals to serotonin is augmented in the presence of a flow-limiting stenosis or total coronary occlusion; and 4) to determine the distribution of microvascular pressures in native and mature collaterals and the distribution of microvascular resistance in myocardium dependent upon stimulated collaterals.

本建议的目的是评估血管反应， 自体和成熟的侧支动脉和小动脉， 神经体液和生理刺激通过直接可视化侧支 狗左心室的微血管。 侧支微血管 将使用两种技术可视化心外膜。 第一、 使用高频射流将湍流引起的运动最小化 通气与心脏周期同步。 第二，心脏的运动 由于收缩将补偿使用计算机控制的 与心动周期同步的频闪落射照明。 频闪照明在视觉上冻结了心脏的运动 通过显微镜视频使微循环可视化 数字化系统 因此，在不受限制的心脏血管反应中， 可以测量30至400微摩尔的微血管。 微血管 压力将使用计算机控制的机电 微量移液器保持器和伺服零位技术。 Colonel将是 在左前降支和左回旋支之间 使用荧光血管造影术。 对本地和 刺激的侧枝将被测量，以测试假设， 天然和刺激的侧枝对神经体液和 生理刺激将取决于初始血管尺寸 类似于非侧支血管。 只有通过这些技术， 显示冠状动脉微循环， 可以在体内直接测量络脉。 具体目标是 本建议涉及：1）确定双方的反应 血管扩张剂（硝酸甘油， 乙酰胆碱）和血管收缩剂（5-羟色胺、内皮素、加压素 和PGF 2 α）; 2)以确定原生侧枝对 灌注压和血管扩张储备降低， 硝酸甘油或腺苷的络脉中存在的， 血流限制性狭窄或完全闭塞; 3）确定是否 在存在5-羟色胺的情况下， 限流性狭窄或完全冠状动脉闭塞;以及4） 确定微血管压力的分布， 成熟侧支和微血管阻力的分布 心肌依赖于刺激的侧枝。