ADENOSINE & K+ATP CHANNELS IN CORONARY FLOW REGULATION (HL49822)

当心脏氧代谢增加时，如在运动中， 供应的冠脉血流量同时增加 更多的氧气进入心脏。通常情况下会有一场非常接近的比赛 在氧气供应和氧气需求的增加之间。这是怎么回事 匹配的发生是冠脉生理学的基本问题。在……里面 患有冠状动脉疾病的人类，氧气供应不足， 由此导致的心肌缺血会导致心绞痛。这个 本项目的目的是检验以下假设 腺苷和/或K+ATP通道(受腺苷影响) 参与冠脉血流的反馈控制 正常情况下，心脏维持充足的氧气供应。钥匙 检验腺苷假说的要素是对 间质腺苷浓度，不能直接 量过了。将使用指示剂稀释实验来获得 轴向分布的多区域血液组织的参数 交换模型(由模拟资源开发) 用来估计间质中腺苷浓度 冠脉血流量和静脉血浆腺苷浓度。 腺苷的作用将通过选择性腺苷来测试。 受体阻滞剂8-苯茶碱及K+-ATP的作用 通道使用选择性通道阻滞剂格列本脲。这个 阻断剂与腺苷浓度的联合使用 测量将严格测试腺苷和/或K+ATP的作用 儿茶酚胺对冠脉血流的控制作用 心脏刺激和冠脉血液自动调节期间 流。这项研究的意义在于，一个基本的机制 将对冠状动脉控制进行研究。

When cardiac oxygen metabolism increases, as during exercise, there is a simultaneous increase in coronary blood flow that supplies more oxygen to the heart. Normally there is a very close match between the increase in oxygen supply and oxygen demand. How this match occurs is the fundamental question in coronary physiology. In humans with coronary artery disease, the oxygen supply is inadequate, and the resulting myocardial ischemia causes anginal chest pain. The purpose of the present project is to test the hypothesis that adenosine and/or K+ATP channels (which are influenced by adenosine) are involved in the feedback control of coronary blood flow that normally maintains an adequate oxygen supply to the heart. The key element in testing the adenosine hypothesis is an estimation of interstitial adenosine concentration, which cannot be directly measured. Indicator-dilution experiments will be used to obtain the parameters for an axially distributed, multiple region, blood-tissue exchan ge model (developed by the Simulation Resource) that will be used to estimate the interstitial adenosine concentration from coronary blood flow and the venous plasma adenosine concentration. The role of adenosine will be tested with a selective adenosine receptor blocking agent, 8-phenyltheophylline, and the role of K+ATP channels with the selective channel blocking agent glibenclamide. The use of the blocking agents in combination with adenosine concentration measurements will critically test the role of adenosine and/or K+ATP channels in controlling coronary blood flow during catecholamine stimulation of the heart and during autoregulation of coronary blood flow. The significance of the research is that a basic mechanism in coronary control will be studied.