ROLE OF ADENOSINE IN HUMAN MYOCARDIAL ISCHEMIA

腺苷在人类心肌缺血中的作用

• 批准号: 3473625
• 负责人: MARC David FELDMAN
• 金额: $ 10.75万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473625
• 关键词: adenosine; angina pectoris; angiography; biomarker; blood chemistry; coronary disorder; coronary sinus; heart catheterization; heart circulation; high performance liquid chromatography; human subject; inosine; intraluminal angioplasty; medical complication; method development; myocardial ischemia /hypoxia; radioimmunoassay; reactive hyperemia; sign /symptom; thermal blood flow measurement

A Metabolic Catheter has been developed which, for the first time, allows accurate measurement of adenosine in the coronary sinus of patients. The long-term goal of this project is to determine what role adenosine plays in the pathogenesis of human myocardial ischemia. If this project can demonstrate that coronary sinus adenosine concentration is an accurate reflection of myocardial ischemia, the physiologic assessment of obstructive coronary artery disease (CAD) visualized at the time of cardiac catheterization will be possible. Aim 1: Develop improved methods for the measurement of adenosine in human blood. Aim 1.1 is to develop procedures to ensure that no significant adenosine is artifactually formed as a result of the breakdown of adenine nucleotides released from platelets or hemolyzed red blood cells. Aim 1.2 is to develop improved procedures to measure adenosine in blood by automated radioimmunoassay. Aim 2: Determine if adenosine is an accurate marker of myocardial ischemia in patients with CAD. Aim 2.1 is to determine if coronary sinus adenosine and inosine release are a more precise metabolic reflection of myocardial ischemia than the current gold standard, coronary sinus lactate. Coronary sinus adenosine, inosine, and lactate will be correlated with the ratio of myocardial blood supply (assessed by thermodilution coronary sinus blood flow) to myocardial demand (assessed by the rate-pressure product). Aim 2.2 is to determine if basal and pacing-induced rises in coronary blood flow in patients with multivessel obstructive coronary disease are in part dependent on adenosine release. Coronary sinus adenosine and inosine levels will be compared between patients with no epicardial or small resistance CAD to those with multivessel CAD. Similar measurements will be repeated during atrial pacing. Aim 2.3 is to determine if reactive hyperemia in humans is mediated by increased production of adenosine. Patients with obstructive CAD undergoing elective percutaneous transluminal angioplasty will have coronary sinus adenosine and inosine levels measured at baseline and during maximal reactive hyperemic flow. Aim 2.4 is to determine if coronary steal is due to increased interstitial adenosine. The amount of coronary steal in CAD patients will be determined by the severity of the initial thallium-201 defect and the presence of delayed redistribution induced by intravenous dipyridamole on quantitative scintigraphy, and correlated with the rise in coronary sinus adenosine and inosine. Aim 3: Determine if adenosine is the link between myocardial ischemia and angina. Aim 3.1 is to determine if patients with predominantly "silent ischemia" have no change or less of rise in coronary sinus adenosine and inosine in response to stress than patients with symptomatic CAD. Aim 3.2 is to determine if ischemia in "Syndrome X" is associated with a rise in coronary sinus adenosine and inosine, which would strengthen the notion that adenosine production in this condition dilates epicardial coronary arterioles, producing subendocardial-to-epicardial steal.

已经开发了一种代谢导管，这是第一次 可以准确测量腺苷的冠状窦 患者。 该项目的长期目标是确定角色 腺苷在人心肌缺血的发病机理中发挥作用。 如果 该项目可以证明冠状窦腺苷浓度 是心肌缺血的准确反射，生理 在可视化的阻塞性冠状动脉疾病（CAD）评估 心脏导管插入的时间将有可能。 目标1：发展 改进的人体血液中腺苷测量的方法。 目的 1.1是制定程序以确保没有明显的腺苷是 腺嘌呤核苷酸崩溃的结果是人为形成的 从血小板或溶血的红细胞释放。 目标1.2是 开发改进的程序，通过自动化测量血液中的腺苷 放射免疫分子。 目标2：确定腺苷是否是准确的标记 CAD患者的心肌缺血。 AIM 2.1是确定是否 冠状窦腺苷和肌苷释放更精确 心肌缺血的代谢反射比目前的黄金 标准，冠状动脉乳酸。 冠状腺苷，肌苷， 乳酸将与心肌供应的比率相关 （通过热稀释冠状窦血流评估）至心肌 需求（由速率压力产品评估）。 目标2.2是确定 如果患者的基础和起搏引起的冠状动脉血流上升 多人阻塞性冠状动脉疾病部分取决于 腺苷释放。 冠状窦腺苷和肌苷水平将是 在没有心外膜或小阻力CAD的患者与 那些带有多系列CAD的人。 将重复类似的测量 在心房起搏期间。 AIM 2.3是确定反应性充血是否在 人类是由腺苷产生增加而介导的。 患者 障碍物CAD经过选修经皮液压 血管成形术将具有冠状窦腺苷和肌苷水平 在基线和最大反应性高血流动时测量。 目的 2.4是确定冠状动脉窃取是否是由于间隙增加引起的 腺苷。 CAD患者的冠状动脉窃取数量将是 由最初的thallium-201-201确定 静脉双吡啶胺引起的延迟重新分布的存在 在定量闪烁显像中，与冠状动脉升高有关 窦腺苷和肌苷。 目标3：确定腺苷是否是链接 在心肌缺血和心绞痛之间。 AIM 3.1是确定是否 主要是“沉默缺血”的患者没有改变或更少的变化 应激响应于压力而不是 有症状CAD的患者。 AIM 3.2是确定是否缺血 “综合征X”与冠状窦腺苷的升高有关 肌苷，这将加强腺苷产生的观念 这种疾病扩展了心外膜冠状动脉，产生 心内膜到心脏的偷窃。