Impact of Aging on Skeletal Muscle Blood Flow Kinetics During Exercise

衰老对运动过程中骨骼肌血流动力学的影响

• 批准号: 8639634
• 负责人: Darren Patrick Casey
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639634
• 关键词: Achievement; Address; Adrenergic Agents; Age; Aging; Attention; Attenuated; Award; Biochemical; Biological Availability; Blood Vessels; Blood flow; Cardiovascular Physiology; Clinic; Complex; Conscious; Contracts; Controlled Study; Data; Educational Status; Elderly; Exercise; Forearm; Gender; Goals; Grant; Heterogeneity; Human; Hyperemia; Individual; Intervention; Kinetics; Knowledge; Laboratories; Learning; Leg; Life; Limb structure; Literature; Lower Extremity; Measures; Mechanics; Mediating; Mentors; Mentorship; Metabolic; Muscle; Muscle Contraction; Nitric Oxide; Oxygen; Oxygen Consumption; Phase; Physical Function; Physical activity; Physiological; Physiology; Property; Publishing; Regulation; Research; Resistance; Rest; Skeletal Muscle; Speed; Structure; Sympathetic Nervous System; Techniques; Time; Tissues; Training; Ultrasonography; United States National Institutes of Health; Upper Extremity; Vasodilation; Vasodilator Agents; Work; adrenergic; age effect; aged; arm; arterial stiffness; healthy aging; improved; innovation; meetings; programs; relating to nervous system; research study; response; sedentary; skills; viscoelasticity; young adult

PROJECT SUMMARY/ABSTRACT During dynamic exercise skeletal muscle blood flow increases rapidly and dramatically (exercise hyperemia) to meet the metabolic needs of the contracting tissue. Aging is associated with an attenuated hyperemic response during dynamic exercise. The mechanisms responsible for increasing blood flow at the onset of exercise as well as maintaining it over time in young adults involves a complex interaction between mechanical factors, the sympathetic nervous system and local metabolic and endothelial derived substances that influence vascular tone. The mechanisms responsible for the observed reductions in exercise blood flow in older humans are not completely clear. The applicant proposes two main goals: 1) to identify mechanisms contributing to the altered vasodilator responses to single muscle contractions and dynamic exercise in aging humans, and 2) to examine the effect of aging on the kinetics of skeletal muscle blood flow/vasodilation during exercise. During the K99/Mentored phase of the grant, the applicant will examine the mechanical, endothelial, and neural alterations in vascular function that occur with aging and determine how these changes relate to the attenuated rapid vasodilator response following a single muscle contraction. In the first portion of the R00/Independent phase of the grant, the applicant will examine the kinetics (rest to steady state transition) of vasodilation during rhythmic exercise and quantify the effects of aging on these responses. In the second portion of the R00 phase, the applicant evaluate whether the attenuated vasodilator response to single muscle contractions and slower kinetics of vasodilation during rhythmic exercise are similar in the upper and lower limbs of older subjects. Lastly, in the third portion of the R00 phase, the applicant will determine whether the changes in flow following single contractions and/or the kinetics of vasodilation in older humans is a result of physiological aging or related to training status. Collectively, the experiments outlined in this proposal focus on the mechanical, endothelial, and neural alterations that occur in the skeletal muscle vasculature with aging and how these changes impact blood flow in exercising muscle. Identifying the mechanisms by which blood flow to contracting muscles is altered with advancing age will help in understanding whether these changes are due to physiological age per se or a result of inactivity. During the K99/Mentored phase of the award the applicant will 1) continue to gain expertise in basic integrative physiology studies in conscious humans, and 2) continue to learn pharmacological and biochemical approaches to study the control of muscle blood flow from a mechanistic standpoint. Additionally, the candidate will gain new research skills and knowledge related to advanced cutting-edge ultrasound techniques and measures of arterial properties (specifically, Shearwave Dispersion Ultrasound Vibrometry; SDUV) under the mentorship of Dr. James Greenleaf (co-mentor). Training in an established and productive laboratory such as that of Dr. Michael Joyner along with the help of Dr. James Greenleaf at the Mayo Clinic will provide opportunities needed to achieve the goals listed above. Importantly, this training will facilitate the achievement of the applicant's long-term goal to develop an internationally-renowned independent research program in cardiovascular physiology.

项目摘要/摘要 在动态运动中 充血）满足收缩组织的代谢需求。衰老与衰减有关 动态运动过程中的高血分反应。负责增加血液流量的机制 运动的发作以及在年轻人中随着时间的推移维持它涉及复杂的相互作用 机械因素，交感神经系统以及局部代谢和内皮衍生物质 那会影响血管音。导致运动血流减少的机制 在老年人中，人类并不完全清楚。 申请人提出了两个主要目标：1）确定导致变化的血管扩张器的机制 对人类衰老的单一肌肉收缩和动态运动的反应，以及2）检查效果 运动过程中骨骼肌血流/血管舒张的动力学衰老。在K99/指导期间 赠款的阶段，申请人将检查血管的机械，内皮和神经改变 衰老发生的功能并确定这些变化与减毒的快速血管扩张剂的关系 单个肌肉收缩后的反应。在赠款的R00/独立阶段的第一部分中， 申请人将检查节奏运动过程中血管舒张的动力学（静态到稳态过渡） 并量化衰老对这些反应的影响。在R00阶段的第二部分中，申请人 评估减弱的血管扩张器对单肌收缩的反应和较慢的动力学 在旧受试者的上肢和下肢中，节奏运动期间的血管舒张相似。最后，在 R00阶段的第三部分，申请人将确定是否以下流量变化 老年人的宫缩和/或血管舒张的动力学是生理衰老的结果或与 培训状况。总的来说，本提案中概述的实验重点是机械， 内皮和神经改变发生在骨骼肌脉管系统中，随着衰老的衰老以及如何 这些变化会影响锻炼肌肉的血流。确定血液流向的机制 随着年龄的增长，收缩肌肉发生了改变 生理年龄本身或无效的结果。 在奖励的K99/指导阶段，申请人将1）继续获得基本方面的专业知识 有意识人类的综合生理研究，以及2）继续学习药理学和生化 从机械角度研究肌肉血流控制的方法。另外， 候选人将获得与高级尖端超声技术有关的新研究技能和知识 和动脉特性（特别是剪力波色散超声振动; SDUV）的度量 詹姆斯·格林利夫（James Greenleaf）博士（联合学）的指导。在一个既定而生产的实验室中的培训 迈克尔·乔伊纳（Michael Joyner）博士在梅奥诊所的詹姆斯·格林利夫（James Greenleaf）博士的帮助下将提供 实现上述目标所需的机会。重要的是，这项培训将有助于 实现申请人的长期目标，以发展国际知名的独立 心血管生理学研究计划。