ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

腺苷

• 批准号: 2702219
• 负责人: ERIC O FEIGL
• 金额: $ 27.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-25 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2702219
• 关键词: adenosine; coronary vessels; dogs; heart circulation; heart metabolism; heart pharmacology; mathematical model; neurotransmitter antagonist; oxygen consumption; potassium channel; purinergic receptor; theophylline

DESCRIPTION: (Adapted from the Applicant's Abstract) When cardiac oxygen metabolism increases, as during exercise, there is a simultaneous increase in coronary blood flow that supplies more oxygen to the heart. How the match between oxygen supply and demand 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. It is postulated that adenosine and/or K+ATP channels (which interact with 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. A mathematical model will be used to calculate 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 these blocking agent 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, cardiac pacing and exercise. The significance of this research is that the basic mechanism of coronary control will be studied. An understanding of normal physiological control is important in itself but is also relevant to pathological states.

描述：（改编自申请人摘要）当心脏氧 新陈代谢增加，因为在运动过程中，同时增加 为心脏提供更多氧气的冠状动脉血流。 如何 氧气供应和需求之间的匹配是根本问题， 冠脉生理学 在患有冠状动脉疾病的人中， 供应不足，由此导致的心肌缺血引起心绞痛。 胸痛 据推测，腺苷和/或K + ATP通道（其 与腺苷相互作用）参与冠状动脉的反馈控制， 正常情况下为心脏提供充足氧气的血流。 检验腺苷假说的关键因素是估计 间质腺苷浓度，不能直接测量。 一 将使用数学模型来计算间质腺苷 冠状动脉血流和静脉血浆腺苷浓度 浓度. 腺苷的作用将用选择性的 腺苷受体阻断剂，8-苯基茶碱，和作用 K + ATP通道与选择性通道阻断剂格列本脲。 的 这些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， 在儿茶酚胺刺激期间控制冠状动脉血流的通道 心脏起搏和锻炼。 其意义 研究的重点是研究冠心病控制的基本机制。 了解正常的生理控制本身就很重要， 也与病理状态有关。