THALLIUM KINETICS IN NORMAL AND ISCHEMIC MYOCARDIUM

目的是为了更好地了解铊-201(T1) 冠脉再灌流条件下的转运动力学 先前的持续性咬合；2)反复短暂的暂时性咬合 缺血导致长时间的缺血后功能障碍；3) 潘生丁的血管扩张作用及其拮抗作用 8-苯基-茶碱，一种特异腺苷拮抗剂。一所主要的中学 目的：研究心肌摄取和洗脱动力学。 一种新型~(99m)Tm标记灌注剂[铜(1-甲基-2-甲基丙基) 1-异腈)6)]在正常条件下，在短暂性缺血和 心肌梗死后。在协议1中，我们将检验假设 在初始正态T1分布之后出现延迟缺陷 (“反向再分布”)犬心内膜下心肌梗死模型 充血心外膜区早期T1摄取增加的结果 与正常区域冲刷相比，后续冲刷速度更快。在第二号议定书中， 开胸狗将经历10次重复的5分钟的暂时性 LAD闭塞时穿插10分钟复流以产生延长 缺血后的“令人惊叹”。我们将调查膜转运 在此模型中，尽管流量恢复且不存在 坏死。在协议3中，我们将比较新的Tc-99m的动力学 双核素T1灌注剂在不同犬模型中的应用研究 短暂性缺血，左前降支阻断3小时后再灌流 在潘生丁之后。在议定书4中，我们建议进一步调查 心内膜/心外膜异常T1冲刷与心内膜/心外膜“偷窃”的机制 一种部分冠状动脉狭窄的犬模型。在这些实验中，我们 将使用茶碱的8-苯基衍生物，它没有交感 作用并单独阻断腺苷受体。在所有的实验中，我们将 使用放射性微球测量局部血流量。在 持续闭塞的复流实验、梗塞范围和危险区域 将被量化，并与流量和T1动力学测量相关联。 冠状动脉疾病仍然是美国人的主要死亡原因 国家和非侵入性放射性核素方法的发展 静息或运动时或药物作用下的心肌灌注评估 压力是提高我们检测心肌梗死的能力的重要一步 缺血，以识别心脏事件的高危患者并 测定心肌存活率。

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.