Coronary Physiology

冠状动脉生理学

• 批准号: 7788878
• 负责人: ERIC O FEIGL
• 金额: $ 39万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-16 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7788878
• 关键词: ATP Receptors; Adenosine; Anemia; Animals; Arginine; Basic Science; Blood; Blood capillaries; Blood flow; Buffers; Canis familiaris; Cavia; Cells; Companions; Coronary; Coronary Arteriosclerosis; Coronary Circulation; Coronary Stenosis; Coronary artery; Couples; Data; Distal; Endothelial Cells; Environment; Equilibrium; Erythrocytes; Exercise; Feedback; Gap Junctions; Grant; Heart; Heart Rate; Hemoglobin; Homeostasis; In Vitro; Infusion procedures; Injection of therapeutic agent; Literature; Measurement; Measures; Mediating; Mediator of activation protein; Metabolic; Microcirculation; Myocardial; Myocardial Ischemia; Myocardium; Nitric Oxide; Nitric Oxide Pathway; Nitric Oxide Synthase; Nitrites; Oxides; Oxygen; Oxygen Consumption; Oxygen measurement, partial pressure, arterial; Perfusion; Physiological; Physiology; Plasma; Production; Public Health; Purinergic P1 Receptors; Purinoceptor; Reading; Research; Role; Schedule; Source; Testing; Time; Vascular Smooth Muscle; Vasodilation; Vasodilator Agents; Venous; Writing; analog; arteriole; capillary; coronary perfusion; coronary vasodilator; deoxyhemoglobin; design; dosage; falls; feeding; pressure; prevent; receptor; research study; response; sensor

DESCRIPTION (provided by applicant): When heart rate increases (as occurs during exercise), coronary blood flow must increase to provide oxygen to the heart to support the augmented myocardial oxygen consumption. The purpose of the proposed research is to discover essential physiological mechanisms that couple coronary blood flow to myocardial oxygen consumption. Without these mechanisms, the heart becomes ischemic and dies. A new hypothesis, with supporting data, is presented where ATP released from red blood cells in the coronary circulation acts as a mediator of local metabolic coronary vasodilation. A plan is presented to quantitatively test the ATP hypothesis during exercise, restricted flow, and anemia with a combination of ATP measurements and ATP-receptor blockade. A second new hypothesis, with supporting data, is presented where deoxyhemoglobin in red blood cells catalyzes the conversion of blood nitrite (NO2-) to nitric oxide (NO) that causes coronary vasodilation. A plan is presented to test the nitrite to nitric oxide hypothesis with nitrite measurements during exercise, restricted flow, and anemia. The unifying concept of this application is that red blood cell hemoglobin acts as an oxygen sensor in the control of coronary blood flow. The two hypotheses explain mechanisms responsible for local metabolic negative feedback control of coronary blood flow. This prevents myocardial ischemia whenever there is an increase in myocardial oxygen consumption. The relevance to public health is that the proposed basic research is fundamental to understanding the normal coronary physiology that underlies coronary artery disease and myocardial ischemia. This is a resubmission of RO1 HL 082781-01-A1 (This time as a modular grant.)

描述（由申请人提供）：当心率增加时（如运动期间发生的），冠状动脉血流量必须增加以向心脏提供氧气，从而支持增加的心肌耗氧量。这项研究的目的是发现将冠状动脉血流与心肌耗氧量结合起来的基本生理机制。如果没有这些机制，心脏就会缺血并死亡。一个新的假设，支持数据，提出了从红细胞释放的ATP在冠状动脉循环作为一个调解人的局部代谢冠状动脉血管舒张。一个计划是在运动，限制流量，和贫血与ATP测量和ATP受体阻断相结合，定量测试ATP假说。第二个新的假设，与支持数据，提出了在红细胞中的脱氧血红蛋白催化血液亚硝酸盐（NO2-）转化为一氧化氮（NO），导致冠状动脉血管扩张。提出了一个计划，以测试亚硝酸盐的一氧化氮假说与亚硝酸盐的测量在运动，限制流动，和贫血。该应用的统一概念是红细胞血红蛋白在冠状动脉血流的控制中充当氧传感器。这两个假设解释了冠状动脉血流局部代谢负反馈控制的机制。当心肌耗氧量增加时，这可防止心肌缺血。与公共卫生的相关性在于，拟议的基础研究对于理解冠状动脉疾病和心肌缺血的正常冠状动脉生理学至关重要。这是RO1 HL 082781 - 01-A1的重新提交（这次作为模块补助金）。