Coronary Physiology

冠状动脉生理学

• 批准号: 7251753
• 负责人: ERIC O FEIGL
• 金额: $ 38.97万
• 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 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7251753
• 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; Magnetic Resonance Spectroscopy; 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; Personal Satisfaction; Physiological; Physiology; Plasma; Production; Public Health; Purinergic P1 Receptors; Purinoceptor; Purpose; Range; Reading; Research; Role; Schedule; Source; Testing; Time; Vascular Smooth Muscle; Vasodilation; Vasodilator Agents; Venous; Writing; analog; arteriole; capillary; concept; coronary perfusion; coronary vasodilator; deoxyhemoglobin; design; dosage; falls; feeding; latent nuclear antigen; 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（如运动时），冠状动脉血流量必须增加，以向心脏提供氧气，以支持增加的心肌耗氧量。本研究的目的是发现冠脉血流量与心肌耗氧量耦合的基本生理机制。没有这些机制，心脏就会缺血而死亡。一个新的假设，与支持的数据，提出了ATP释放的红细胞在冠状动脉循环作为局部代谢性冠状动脉血管舒张的介质。提出了一种计划，通过ATP测量和ATP受体阻断相结合，在运动、受限血流和贫血期间定量测试ATP假设。第二个新的假设，有支持的数据，提出了红细胞中的脱氧血红蛋白催化血液中亚硝酸盐（NO2-）转化为一氧化氮（NO），导致冠状动脉血管舒张。提出了一种计划，通过在运动、受限血流和贫血期间测量亚硝酸盐来测试亚硝酸盐对一氧化氮的假设。该应用的统一概念是红细胞血红蛋白在控制冠状动脉血流中充当氧传感器。这两种假说解释了局部代谢负反馈控制冠状动脉血流的机制。当心肌耗氧量增加时，这可以防止心肌缺血。与公共卫生相关的是，拟议的基础研究是理解冠状动脉疾病和心肌缺血背后的正常冠状动脉生理学的基础。这是RO1 HL 082781-01-A1的重新提交（这次是模块化授权）。