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

腺苷

• 批准号: 6119778
• 负责人: ERIC O FEIGL
• 金额: $ 2.28万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-16 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6119778
• 关键词: Mammalia; bioengineering /biomedical engineering; biomedical resource; human tissue; model design /development; technology /technique

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.

当心脏氧代谢增加时，如在运动期间， 同时冠状动脉血流量增加， 为心脏提供更多氧气。 通常有一个非常接近的比赛 氧气供应量和氧气需求量之间的关系。 这如何 匹配发生是冠状动脉生理学中的基本问题。 在 患有冠状动脉疾病的人，氧气供应不足， 并且所导致的心肌缺血引起心绞痛性胸痛。 的 本项目的目的是检验假设， 腺苷和/或K + ATP通道（受腺苷影响） 参与冠状动脉血流的反馈控制， 正常情况下维持心脏充足的氧气供应。 关键 检验腺苷假设的一个要素是估计 间质腺苷浓度，不能直接 测定了 将使用指示剂稀释实验获得 用于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）将 用于估计间质腺苷浓度， 冠状动脉血流量和静脉血浆腺苷浓度。 腺苷的作用将用选择性腺苷 受体阻断剂8-苯基茶碱和K + ATP的作用 选择性通道阻断剂格列本脲。 的 阻断剂与腺苷浓度的组合的用途 测量将严格测试腺苷和/或K + ATP的作用， 通道在控制冠状动脉血流中的作用 刺激心脏和在冠状动脉血液的自动调节期间 流 本研究的意义在于揭示了一个基本的机制， 将研究冠状动脉控制。