ADENOSINE & K/ATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

腺苷

• 批准号: 2225869
• 负责人: ERIC O FEIGL
• 金额: $ 23.75万
• 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 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225869
• 关键词: adenosine; adrenergic agents; alpha adrenergic agent; dosage; exercise; heart circulation; heart metabolism; heart pharmacology; indicator dilution test; mathematical model; oxygen consumption; potassium channel; vasodilation

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. 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. Indicator-dilution experiments will be used to obtain the parameters for a mathematical model that will then 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-phenyltheophyl-line, and the role of K+ATP channels with the selective channel blocking agent, glibenclamide. The use of these 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, 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.

当心脏氧代谢增加时，如在运动中，有 提供更多氧气的冠脉血流量同时增加 直击内心。通常情况下，增长与增长之间存在非常接近的匹配 在氧气供应和氧气需求方面。这种匹配是如何发生的 冠状动脉生理学中的基本问题。在患有冠状动脉疾病的人类中 动脉疾病，氧气供应不足，从而导致 心肌缺血会引起心绞痛。 据推测，腺苷和/或K+ATP通道(相互作用 与腺苷一起参与冠脉血液的反馈控制 正常情况下维持对心脏的充足氧气供应的血流。这个 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。 将通过指示剂稀释实验获得以下参数 一个数学模型，然后将被用来计算间隙 冠脉血流量和静脉血浆中的腺苷浓度 腺苷浓度。腺苷的作用将通过一项 选择性腺苷受体阻滞剂8-苯基茶碱和 K+ATP通道与选择性通道阻滞剂的作用， 格列本脲。将这些封闭剂与 腺苷浓度测量将关键地测试 腺苷和/或K+ATP通道在冠脉血流控制中的作用 儿茶酚胺对心脏的刺激、心脏起搏和运动。 本研究的意义在于冠脉病变的基本机制 将对控制进行研究。对正常生理学的认识 控制本身很重要，但也与病理有关 各州。