ADENOSINE & K/ATP CHANNEL CONTROL OF CORONARY BLOOD FLOW

当心脏氧代谢增加时，如在运动期间， 同时增加冠状动脉血流量，提供更多氧气 打到心脏 通常情况下， 氧气供应和氧气需求。 这场比赛是如何发生的， 冠状动脉生理学的基本问题。 在患有冠心病的人中， 动脉疾病时，氧气供应不足， 心肌缺血引起心绞痛性胸痛。 据推测，腺苷和/或K+ATP通道（其相互作用 与腺苷）参与冠状动脉血液的反馈控制 正常情况下维持心脏充足氧气供应的血流。 的 检验腺苷假设的关键因素是估计 间质腺苷浓度，不能直接测量。 将使用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 冠状动脉血流和静脉血浆腺苷浓度 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通道与选择性通道阻断剂的作用， 格列本脲 这些封闭剂与以下物质的组合使用是优选的： 腺苷浓度测量将严格测试 腺苷和/或K+ATP通道在控制冠状动脉血流中的作用 儿茶酚胺刺激心脏，心脏起搏和运动。 本研究的意义在于探讨了冠心病的基本发病机制 将研究控制。 了解正常的生理 控制本身很重要，但也与病理学有关。 states.

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.