Muscle Reflex Control of the Coronary Circulation

冠状动脉循环的肌肉反射控制

基本信息

项目摘要

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):主要研究者的长期目标是研究调节人体循环的机制。该计划的具体目标是更好地了解运动期间调节冠状动脉血流的机制。该提案的一个关键特点是我们将使用双功超声来测量左冠状动脉前降支的冠状动脉血流量。该应用的具体目标是:我们将证明在握力过程中会发生冠状动脉收缩(即冠状血管阻力增加)。我们还将确定这种限制的机制。我们假设最大自主收缩 (MVC) 的百分比较高时会发生收缩。我们假设这种效应主要是由于肌肉机械感受反射的参与所致。我们还将确定冠状血管收缩反应是否会随着衰老和心力衰竭(HF)而增强。我们假设情况确实如此,并且这种强化效应是由于老年人和心衰患者肌肉机械反射的激活增强所致。然后我们将研究调节人类冠状动脉收缩反应的传出机制。我们假设静脉使用 1-阻滞剂(酚妥拉明)会阻断收缩机制,在存在急性静脉注射 2-阻滞剂(普萘洛尔)和高氧(一种增加一氧化氮氧化猝灭的干预措施)的情况下会加剧。在过去的5至6年里,我们努力开发双重方法来检查肾血流速度。由此产生了一系列论文,这些论文定义了肌肉机械感受器在正常人、老年人和心力衰竭患者的肾脏产生交感神经收缩方面的作用。最近,我们将注意力集中在有意识的人类冠状动脉血流的调节上。我们通过使用心内多普勒线侵入性测量冠状动脉血流量开始了这项工作。然后,我们进行了研究,测量经手术治疗的冠状动脉疾病受试者的左乳内动脉旁路移植物的流速。最近,我们收集了检查天然冠状动脉中冠状动脉血流的试点数据。这种方法的开发花费了数年时间。我们现在准备利用这种方法来解决控制正常志愿者、心力衰竭患者和老年人左前降支血流的机制。了解运动期间控制血流的机制是一个重要的研究领域,因为流向心脏的血流是一个人进行日常生活活动的能力的关键决定因素。更好地了解神经系统调节冠状循环的能力将使我们有机会开发新的方法来治疗冠状动脉调节受损的疾病(例如心力衰竭)。公众健康相关性:我们将在运动过程中无创地检查冠状动脉血流。了解运动期间控制血流的机制是一个重要的研究领域,因为流向心脏的血流是一个人进行日常生活活动的能力的重要决定因素。更好地了解神经系统调节冠状循环的能力将使我们有机会开发新的方法来治疗冠状动脉调节受损的疾病(例如心力衰竭)。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Lawrence I Sinoway其他文献

Self-Reported Social Determinants of Health and Area-Level Social Vulnerability
自我报告的健康和地区社会脆弱性的社会决定因素
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    13.8
  • 作者:
    Emily Brignone;Keith LeJeune;Amanda E Mihalko;Amy L Shannon;Lawrence I Sinoway
  • 通讯作者:
    Lawrence I Sinoway

Lawrence I Sinoway的其他文献

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{{ truncateString('Lawrence I Sinoway', 18)}}的其他基金

Core A - Administrative Core
核心 A - 行政核心
  • 批准号:
    10117108
  • 财政年份:
    2017
  • 资助金额:
    $ 38.78万
  • 项目类别:
Project 1: The Muscle Reflex: Modes of Engagement and Circulatory Consequences
项目 1:肌肉反射:参与模式和循环系统后果
  • 批准号:
    10117110
  • 财政年份:
    2017
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    10387381
  • 财政年份:
    2016
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8262017
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8634595
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
PENN STATE CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8365251
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8490522
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8490521
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8473975
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:
Penn State Clinical and Translational Science Institute
宾夕法尼亚州立大学临床与转化科学研究所
  • 批准号:
    8270470
  • 财政年份:
    2011
  • 资助金额:
    $ 38.78万
  • 项目类别:

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