Muscle Reflex Control of the Coronary Circulation

冠状动脉循环的肌肉反射控制

• 批准号: 8096741
• 负责人: Lawrence I Sinoway
• 金额: $ 38.78万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8096741
• 关键词: Abbreviations; Activities of Daily Living; Acute; Address; Adenosine Triphosphate; Adrenergic beta-Antagonists; Aging; Anterior; Anterior Descending Coronary Artery; Area; Arteries; Attention; Attenuated; Blood; Blood Circulation; Blood Flow Velocity; Blood Pressure; Blood flow; Body mass index; Bypass; Cardiac Catheterization Procedures; Clinical Research; Conscious; Coronary; Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary Circulation; Coronary artery; Data; Exercise; Fatigue; Goals; Health; Heart; Heart Rate; Heart failure; Human; Hyperoxia; Institutional Review Boards; Intervention; Intravenous; Kidney; Laboratories; Left; Lower Body Negative Pressure; Manuscripts; Measures; Mechanoreceptors; Methods; Muscle; Nerve; Nervous system structure; Nitric Oxide; Norepinephrine; Operative Surgical Procedures; P2X-receptor; Paper; Patients; Persons; Phentolamine; Pilot Projects; Positron-Emission Tomography; Principal Investigator; Propranolol; Publishing; Purinoceptor; Reflex action; Reflex control; Regulation; Renal Blood Flow; Resistance; Role; Series; Sympathetic Nervous System; Testing; Ultrasonography; Vascular resistance; Vasoconstrictor Agents; Work; aged; base; biceps brachii muscle; constriction; design; human subject; internal thoracic artery; novel; programs; response; volunteer

DESCRIPTION (provided by applicant): The long-range goals of the principal investigator are to examine mechanisms that regulate the circulation in humans. The specific goals of this program are to better understand the mechanisms regulating coronary blood flow during exercise. A key feature of this proposal is that we will use duplex ultrasound to measure coronary blood flow in the left anterior descending coronary artery. The specific aims of this application are: We will demonstrate that coronary constriction (i.e. a rise in coronary vascular resistance) occurs during handgrip. We will also determine the mechanism for this constriction. We hypothesize that constriction will occur at high percentages of maximal voluntary contraction (MVC). We hypothesize that this effect will be due predominantly to engagement of the muscle mechanoreflex. We will also determine if coronary vasoconstrictor responses to handgrip are enhanced with aging and heart failure (HF). We hypothesize that this will be the case and that this accentuated effect will be due to heightened activation of muscle mechanoreflexes in the aged and HF. We will then examine the efferent mechanisms that regulate coronary constrictor responses in humans. We hypothesize that constrictor mechanisms will be blocked by the intravenous use of a 1-blocker (phentolamine), accentuated in the presence of acute intravenous 2-blocker (propranolol), and in the presence of hyperoxia (an intervention to increase the oxidative quenching of nitric oxide). Over the past 5 to 6 years we have worked hard to develop the duplex method to examine renal blood flow velocity. This has resulted in a series of papers that have defined the role of muscle mechanoreceptors in generating sympathetic constriction to the kidney in normal humans, the aged and in HF. Recently we have focused attention on the regulation of blood flow in coronary arteries of conscious humans. We began this effort by invasively measuring coronary blood flow using an intracardiac Doppler wire; we then performed studies measuring flow velocity in left internal mammary artery bypass grafts in subjects with surgically treated coronary artery disease. Most recently we have gathered pilot data examining coronary flow in native coronary arteries. This method has taken several years to develop. We are now poised to utilize this method to address the mechanisms that control blood flow to the left anterior descending artery in normal volunteers, in those with HF, and in the aged. Understanding the mechanisms that control blood flow during exercise is an important area of study as blood flow to the heart is a crucial determinant of a person's ability to perform the activities of daily living. Greater understanding of the nervous system's ability to regulate the coronary circulation will afford us the opportunity to develop novel ways of treating conditions where coronary regulation is impaired such as HF. PUBLIC HEALTH RELEVANCE: We will examine coronary blood flow non-invasively during exercise. Understanding the mechanisms that control blood flow during exercise is an important area of study as blood flow to the heart is an important determinant of a person's ability to perform the activities of daily living. Greater understanding of the nervous system's ability to regulate the coronary circulation will afford us the opportunity to develop novel ways of treating conditions where coronary regulation is impaired such as HF.

描述（由申请人提供）：主要研究者的远程目标是检查调节人类循环的机制。该计划的具体目标是更好地了解调节运动过程中冠状动脉血流的机制。该提案的一个关键特征是，我们将使用双工超声来测量左前降冠状动脉的冠状动脉血流。该应用的具体目的是：我们将证明冠状动脉收缩（即冠状动脉血管抗性的升高）在手工夹期间发生。我们还将确定这种收缩的机制。我们假设收缩将以最大自愿收缩（MVC）的高百分比发生。我们假设这种效果主要是由于肌肉机械曲线的互动。我们还将确定随着衰老和心力衰竭（HF）的增强冠状动脉血管收缩反应。我们假设情况将是这种情况，并且这种强调的效果将是由于老年和HF的肌肉机械逆流的激活而引起的。然后，我们将研究调节人类冠状动脉收缩反应的传出机制。我们假设，在存在急性静脉注射2阻滞剂（普萘洛尔）的情况下，静脉内使用1阻滞剂（苯戊酰胺）将阻止收缩机制，并在存在高氧（一种干预措施）的情况下加剧。在过去的5到6年中，我们一直在努力开发双链方法来检查肾脏血流速度。这导致了一系列论文，这些论文定义了肌肉机械感受器在正常人，年龄和HF中对肾脏产生交感神经的作用。最近，我们将注意力集中在有意识人类的冠状动脉动脉中的血流调节上。我们通过使用心脏内多普勒电线对冠状动脉血流进行了侵入性测量开始了这一努力。然后，我们进行了研究，测量了手术治疗冠状动脉疾病的受试者左乳腺动脉旁路移植物中流速的研究。最近，我们收集了研究中冠状动脉冠状动脉流动的试点数据。这种方法已经花费了数年的时间来开发。现在，我们有望利用这种方法来解决正常志愿者，HF和年龄较大的正常志愿者中左前降动脉的机制。理解在运动过程中控制血液流动的机制是一个重要的研究领域，因为血液流向心脏是人们进行日常生活活动能力的关键决定因素。对神经系统调节冠状动脉循环的能力的更多了解将使我们有机会开发新的治疗冠状动脉调节状况的方法，例如HF。公共卫生相关性：我们将在运动期间非侵入性检查冠状动脉血流。理解在运动过程中控制血液流动的机制是一个重要的研究领域，因为血液流向心脏是人们进行日常生活活动能力的重要决定因素。对神经系统调节冠状动脉循环的能力的更多了解将使我们有机会开发新的治疗冠状动脉调节状况的方法，例如HF。