Noninvasive assessment of microvascular function in aging

衰老过程中微血管功能的无创评估

• 批准号: 8451316
• 负责人: Jill M Slade
• 金额: $ 18.13万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8451316
• 关键词: ATP Synthesis Pathway; Adult; Aerobic Exercise; Age; Aging; Arteries; Automobile Driving; Bioenergetics; Blood; Blood Vessels; Blood Volume; Blood flow; Cell Respiration; Clinical; Consensus; Data; Detection; Diabetes Mellitus; Disease; Disease Progression; Elderly; Equilibrium; Evaluation; Exercise; Foundations; Functional Magnetic Resonance Imaging; Goals; Health; Image; Impairment; Individual; Kinetics; Laboratory Study; Lower Extremity; Magnetic Resonance Spectroscopy; Measures; Mediating; Metabolism; Methods; Microcirculation; Monitor; Muscle; Muscle function; Myopathy; Outcome; Oxygen; Oxygen Consumption; Performance; Perfusion; Peripheral; Peripheral arterial disease; Phase; Phosphocreatine; Phosphorus; Physical Function; Play; Population; Protocols documentation; Publishing; Recovery; Regulation; Rodent; Role; Severity of illness; Spectrum Analysis; Time; Tissues; Training; Vascular Diseases; Vasodilation; age effect; age related; aged; arteriole; base; blood oxygen level dependent; functional decline; improved; muscle metabolism; response; sedentary; tool; young adult

DESCRIPTION (provided by applicant): The microvasculature is critical for the control of blood flow and tissue perfusion. Compromised microvascular function occurs during aging as well as several disease states including diabetes and peripheral arterial disease and may contribute to compromised muscle performance within these populations. Unfortunately, practical measures for assessing microvascular function are lacking. With the advent of muscle functional magnetic resonance imaging (fMRI) using blood oxygen level- dependent imaging (BOLD), peripheral microvascular function can be assessed noninvasively. Our studies have shown that muscle BOLD responses are sensitive to blood volume and oxygenation changes and are increased in magnitude in young endurance trained adults when compared to sedentary adults. Preliminary data also suggest an age related decline in BOLD responses and slowing of muscle oxygen kinetics. A reduced BOLD response is important because it indicates reduced muscle perfusion which impacts muscle metabolism and muscle function. The overall purpose of these studies is to exploit muscle BOLD to assess microvascular function in elderly adults. In addition, these studies will also contribute to the understanding of the bioenergetic consequences of aging. Aim 1 will examine the effect of age on muscle BOLD by comparing single contraction mediated responses in young versus elderly adults. We will also examine the effect of age on phosphocreatine (PCr) recovery kinetics; PCr kinetics reflect oxidative ATP synthesis. These outcomes together will allow us to integrate microvascular function with oxygen consumption and ATP synthesis. Aim 2 will examine the influence of aerobic exercise on the muscle BOLD response in sedentary elderly adults. Echo planar fMRI will be used to acquire muscle BOLD images; phosphorus spectroscopy will be used to evaluate PCr kinetics. Muscle BOLD is an important measure because it reflects muscle perfusion and we suggest this is a critical parameter that is lost with aging. Imbalances between perfusion and metabolism may contribute to age related muscle impairment. Our proposed studies are consistent with an emerging consensus that the initial vascular responses are pivotal in vascular control and function. These studies will provide a strong foundation for a noninvasive assessment tool that evaluates microvascular function and will show the ability of aerobic exercise to improve microvascular function in elderly adults. As the U.S. older adult population is nearly 50 million strong and growing, understanding the factors related to poor physical function is imperative. Our long-term goal is to establish noninvasive methods for assessing microvascular and muscle function that can be used in vascular and muscle disease detection and monitoring.

描述（由申请人提供）： 微脉管系统对于控制血流和组织灌注至关重要。微血管功能损害发生在衰老期间以及包括糖尿病和周围动脉疾病在内的几种疾病状态，并可能导致这些人群中的肌肉表现受损。不幸的是，缺乏评估微血管功能的实际措施。随着肌肉功能磁共振成像（fMRI）的出现，使用血氧水平依赖性成像（BOLD），可以无创地评估周围微血管功能。我们的研究表明，与久坐的成年人相比，在年轻耐力训练的成年人中，肌肉大胆的反应对血容量和氧合变化敏感，并且在年轻耐力训练的成年人中增加了幅度。初步数据还表明，大胆反应和肌肉氧动力学的减慢相关。减少的大胆反应很重要，因为它表明肌肉灌注减少，这会影响肌肉代谢和肌肉功能。这些研究的总体目的是利用肌肉粗体来评估老年人的微血管功能。此外，这些研究还将有助于理解衰老的生物能后果。 AIM 1将通过比较年轻人与老年人的单个收缩介导的反应来检查年龄对肌肉大胆的影响。我们还将检查年龄对磷酸磷酸（PCR）恢复动力学的影响； PCR动力学反映了氧化性ATP合成。这些结果将使我们能够将微血管功能与氧气消耗和ATP合成整合。 AIM 2将检查有氧运动对久坐的老年人肌肉大胆反应的影响。 Echo Planar fMRI将用于获取肌肉大胆的图像；磷光谱法将用于评估PCR动力学。肌肉大胆是一个重要的措施，因为它反映了肌肉灌注，我们建议这是随着衰老而丢失的关键参数。灌注和代谢之间的失衡可能导致与年龄相关的肌肉障碍。我们提出的研究与新兴的共识一致，即初始血管反应在血管控制和功能中是关键的。这些研究将为评估微血管功能的非侵入性评估工具提供坚实的基础，并将显示有氧运动改善老年人微血管功能的能力。由于美国老年人人口近5000万强，并且不断增长，因此必须了解与身体差有关的因素。我们的长期目标是建立无创方法来评估可用于血管和肌肉疾病检测和监测的微血管和肌肉功能。

项目成果

Aerobic Exercise Improves Microvascular Function in Older Adults.

• DOI: 10.1249/mss.0000000000001854
• 发表时间: 2019-04
• 期刊: Medicine and science in sports and exercise
• 影响因子: 4.1
• 作者: Hurley DM;Williams ER;Cross JM;Riedinger BR;Meyer RA;Abela GS;Slade JM
• 通讯作者: Slade JM