ADENOSINE & KATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

腺苷

• 批准号: 2910552
• 负责人: ERIC O FEIGL
• 金额: $ 27.89万
• 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/2910552
• 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：(改编自申请人的摘要)当心脏供氧 新陈代谢增加，就像在锻炼时，同时增加 在冠状动脉血流中，为心脏提供更多的氧气。怎么了？ 氧气供需匹配是全社会面临的根本问题 冠脉生理学。在患有冠状动脉疾病的人类中，氧气 供应不足，由此导致的心肌缺血导致心绞痛 胸口痛。据推测，腺苷和/或K+ATP通道( 与腺苷相互作用)参与冠脉的反馈控制 正常情况下维持充足氧气供应给心脏的血液流动。 检验腺苷假说的关键因素是对 间质腺苷浓度，不能直接测量。一个 将使用数学模型来计算间质腺苷 冠脉血流量和静脉血浆腺苷浓度 集中精神。腺苷的作用将通过选择性的 腺苷受体阻滞剂8-苯基茶碱的作用 K+ATP通道用选择性通道阻滞剂格列本脲。这个 这些阻滞剂与腺苷浓度结合使用 测量将严格测试腺苷和/或K+ATP的作用 儿茶酚胺刺激时控制冠脉血流量的通道 心脏、心脏起搏和运动。这件事的意义 研究内容是对冠状动脉控制的基本机制进行研究。 了解正常的生理控制本身很重要，但 也与病理状态有关。