THALLIUM KINETICS IN NORMAL AND ISCHEMIC MYOCARDIUM

正常和缺血心肌中的铊动力学

• 批准号: 3338510
• 负责人: George Allan Beller
• 金额: $ 17.99万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-08-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338510
• 关键词: chemical reaction; coronary disorder; coronary vasodilator; disease /disorder proneness /risk; exercise; heart circulation; heart disorder diagnosis; heart imaging /visualization /scanning; heart pharmacology; human subject; myocardial ischemia /hypoxia; noninvasive diagnosis; radionuclide diagnosis; vasodilation

The objective is to gain a better understanding of thallium-201 (T1) transport kinetics under conditions of 1) coronary reperfusion following prior sustained occlusion; 2) repetitive brief periods of transient ischemia producing prolonged post-ischemic dysfunction; and 3) dipyridamole-induced vasodilation followed by antagonism with 8-phenyl-theophylline, a specific adenosine antagonist. A major secondary objective is the investigation of myocardial uptake and washout kinetics of a new technetium-99m labeled perfusion agent [Cu(1-methyl 2-methosypropyl 1-isonitrile)6)] under normal conditions, during transient ischemia and after myocardial infarction. In Protocol 1 we will test the hypothesis that delayed defect appearance after an initial normal T1 distribution ("reverse redistribution") in a canine model of subendocardial infarction results from early increased T1 uptake in hyperemic epicardial zones and subsequent faster washout compared to normal zone washout. In Protocol 2, open chest dogs will undergo 10 repetitive 5 minute periods of transient LAD occlusion interspersed by 10 minutes of reflow to produce prolonged post-ischemic "stunning". We will investigate whether membrane transport of T1 is altered in this model despite flow recovery and absence of necrosis. In Protocol 3, we will compare the kinetics of a new Tc-99m perfusion agent with T1 using dual isotope studies in various canine models of transient ischemia, reperfusion after 3 hrs of LAD occlusion and following dipyridamole. In Protocol 4, we propose to further investigate the mechanism of abnormal T1 washout and endocardial/epicardial "steal" in a canine model of a partial coronary stenosis. In these experiments we will employ an 8-phenyl derivative of theophylline which has no sympathetic effects and solely blocks adenosine receptors. In all experiments, we will measure regional blood flow employing radioactive microspheres. In the sustained occlusion with reflow experiments, infarct size and risk area will be quantitated and correlated with flow and T1 kinetic measurements. Coronary artery disease is still the major cause of death in the United States and the development of noninvasive radionuclide approaches to assessing myocardial perfusion at rest or during exercise or pharmacologic stress is an important step in enhancing our ability to detect myocardial ischemia, to identify patients at high risk for a cardiac event and to determine myocardial viability.

目的是更好地了解铊-201（T1） 1）冠状动脉再灌注后的转运动力学 既往持续性闭塞; 2）反复短暂的短暂性 局部缺血产生长期的局部缺血后功能障碍;和3） 双嘧达莫诱导的血管舒张，随后拮抗 8-苯基茶碱，一种特异性腺苷拮抗剂。 A主要中学 目的：研究心肌摄取和洗脱动力学， 一种新的~（99）Tc标记的灌注剂[Cu（1-甲基-2-甲氧基丙基 1-异腈）6）]，在正常条件下，在短暂缺血和 心肌梗死后。 在方案1中，我们将测试假设 在初始正态T1分布后延迟缺陷出现 （“反向再分布”）在犬内膜下梗死模型中的作用 充血心外膜区早期T1摄取增加的结果， 与正常区域冲洗相比，后续冲洗更快。 在议定书2中， 开胸犬将经历10次重复的5分钟短暂 LAD闭塞穿插10分钟的再流， 缺血后的“眩晕” 我们将研究膜转运是否 在该模型中，尽管血流恢复和缺乏T1， 坏死 在方案3中，我们将比较新的Tc-99 m 在各种犬模型中使用双同位素研究的T1灌注剂 短暂缺血，LAD闭塞3小时后再灌注， 在潘生丁之后 在第4号议定书中，我们建议进一步调查 T1异常洗脱和心内膜/心外膜“盗血”的机制 冠状动脉部分狭窄的犬模型。 在这些实验中，我们 将使用茶碱的8-苯基衍生物， 影响并单独阻断腺苷受体。 在所有实验中，我们将 使用放射性微球测量局部血流量。 在 持续闭塞与再流实验、梗死面积和危险区 将被定量并与流量和T1动力学测量相关。 冠状动脉疾病仍然是美国的主要死因 发展非侵入性放射性核素方法， 评估静息或运动期间的心肌灌注或药理学 应激是增强我们检测心肌细胞的能力的重要一步， 缺血，以识别处于心脏事件高风险的患者，并 测定心肌存活率。