ADENOSINE AND MYOCARDIAL ISCHEMIA

一种代谢导管已经被开发出来，这是第一次， 允许准确测量冠状静脉窦中的腺苷 病人。这个项目的长期目标是确定什么角色 腺苷在人类心肌缺血的发病机制中起作用。如果 本项目可以证明，冠状静脉窦腺苷浓度 是心肌缺血的准确反映，生理学上 梗阻性冠状动脉疾病(CAD)的可视化评估 心导管术的时间将是可能的。目标1：发展 人血中腺苷测定方法的改进。目标 1.1是制定程序，以确保没有显著的腺苷 人工形成的，是腺嘌呤核苷酸分解的结果 从血小板或溶血的红细胞中释放。目标1.2旨在 开发改进的程序，通过自动测量血液中的腺苷 放射免疫分析。目标2：确定腺苷是否是一个准确的标记物 冠心病患者的心肌缺血程度。目标2.1是确定是否 冠状静脉窦腺苷和肌苷的释放更精确 心肌缺血的代谢反应比目前的金 标准，冠状静脉窦乳酸。冠状静脉窦腺苷，肌苷， 乳酸将与心肌供血比相关 (通过热稀释冠状静脉窦血流评估)到心肌 需求(通过利率-压力乘积进行评估)。目标2.2是为了确定 基础起搏和起搏引起的患者冠脉血流量增加 伴多支血管梗阻性冠状动脉疾病部分依赖于 腺苷释放。冠状静脉窦的腺苷和肌苷水平将 无心外膜或冠心病小阻力的患者之间的比较 有多支冠状动脉病变的患者。类似的测量将重复进行 在心房起搏期间。目标2.3是确定反应性充血是否在 人类是通过增加腺苷的产生来调节的。患有疾病的患者 选择性经皮腔内介入治疗阻塞性CAD 血管成形术将有冠状静脉窦腺苷和肌苷水平 在基线和最大反应性充血血流期间测量。目标 2.4用于确定冠状动脉窃血是否由间质增加所致 腺苷。冠心病患者的冠状动脉盗取量将是 由最初的铊-201缺陷的严重程度和 静脉注射潘生丁引起延迟再分布的存在 在定量核素扫描上，并与冠状动脉病变的增加相关 腺苷和肌苷。目标3：确定腺苷是否是联系 心肌缺血和心绞痛之间的关系。目标3.1是确定 以“无症状性脑缺血”为主的患者无变化或减少 冠状静脉窦腺苷和肌苷在应激反应中的升高 有症状的冠心病患者。目标3.2是确定脑缺血是否 “X综合征”与冠状静脉窦腺苷升高和 肌苷，这将加强腺苷产生的概念 这种情况使心外膜冠状动脉扩张，产生 心内膜下至心外膜下偷窃。

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.