Work of Breathing and Oxidative Stress in COPD: Impact on Blood Flow and Fatigue

慢性阻塞性肺病 (COPD) 中的呼吸和氧化应激作用：对血流和疲劳的影响

• 批准号: 8625822
• 负责人: MARKUS AMANN
• 金额: $ 24.4万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2016-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8625822
• 关键词: Adverse effects; Antioxidants; Ascorbic Acid; Attenuated; Bioenergetics; Biological Availability; Blood flow; Characteristics; Chronic Obstructive Airway Disease; Data; Deterioration; Disease; Dyspnea; Environmental air flow; Exercise; Exercise Tolerance; Fatigue; Free Radicals; Gases; Generations; Grant; Health Status; Human; Individual; Infusion procedures; Intravenous; Leg; Limb structure; Link; Mechanical Ventilators; Mediating; Methods; Muscle; Muscle Fatigue; Muscle function; Nitric Oxide; Oxidative Stress; Oxygen; Pathway interactions; Patients; Performance; Peripheral; Physical Rehabilitation; Play; Population; Predisposition; Principal Investigator; Process; Public Health; Quality of life; Rehabilitation therapy; Research; Respiratory Diaphragm; Respiratory Muscles; Role; Time; Tissues; Venous; Work; Work of Breathing; density; exhaustion; heliox; improved; novel; pressure; prevent; quadriceps muscle; respiratory; restricted physical activity; sedentary; vasoconstriction

Principal Investigator (Last, First): Amann, Markus ABSTRACT Patients with COPD are limited in their daily activities because of exercise limitation that can be sufficiently severe to impair simple everyday tasks. The proposed research will examine novel mechanisms that might contribute to this severe limitation in exercise tolerance and also determine how exercise tolerance might be improved. Specifically, we will assess the role of excessive respiratory muscle work, a characteristic of COPD patients, and elevated oxidative stress during exercise in this population. Additionally, we will assess whether the increased work of breathing is a significant contributor to the increased levels of oxidative stress during exercise in patients with COPD. We will a) use a mechanical ventilator in combination with a reduced density gas mixture to reduce the work of breathing during cycle exercise and b) use venous infusion of vitamin C during cycle exercise to examine the effects of both, the reduced work of breathing and the reduced oxidative stress on muscle fatigue in the exercising legs. We will use a novel combination of methods to provide a sensitive, reproducible, objective means of quantifying limb muscle fatigue. We will further examine whether these proposed effects on limb fatigue are, in part, due to blood flow and oxygen (O2) transport to the limbs and how this is influenced by the work of breathing and oxidative stress. In healthy subjects it has been shown that a reduction in respiratory muscle work increases blood flow and O2 transport to the limbs. Also in healthy subjects, we have recently revealed that increases in blood flow / O2 transport to the working legs significantly reduces muscle fatigue and improves exercise tolerance. Furthermore, it has been shown that a reduction in oxidative stress also increases blood flow / O2 delivery during exercise in older healthy individuals, however, there are currently no data on the effects of oxidative stress on limb blood flow / O2 transport in COPD patients during exercise. In view of the significantly increased work of breathing required during exercise and the substantially increased oxidative stress in COPD patients, we expect the effects of reducing the impact of these factors on limb muscle fatigue to be even greater than in healthy subjects. We propose that this research will provide new effective methods to improve exercise capacity during the rehabilitation of patients with COPD by allowing them to improve endurance of their locomotor muscles. It is anticipated that this improvement in the rehabilitation process will prevent the deterioration of muscle function which is currently prevalent in the sedentary COPD population.

首席研究员（姓、名）：Amann、Markus 抽象的 慢性阻塞性肺病 (COPD) 患者的日常活动受到限制，因为运动限制足以 严重影响简单的日常任务。拟议的研究将检验可能的新机制 导致运动耐量的严重限制，并决定运动耐量如何可能 改善了。具体来说，我们将评估呼吸肌过度工作的作用，这是呼吸肌过度工作的一个特征 慢性阻塞性肺病患者，以及该人群运动期间氧化应激升高。此外，我们将评估 呼吸做功的增加是否是氧化水平增加的一个重要因素 COPD 患者运动期间的压力。我们将 a) 将机械呼吸机与 降低密度的气体混合物，以减少循环运动期间的呼吸功和 b) 使用静脉 在循环运动期间输注维生素 C，以检查呼吸功减少和呼吸功减少的影响 减少运动腿部肌肉疲劳的氧化应激。我们将使用一种新颖的组合 方法提供灵敏、可重复、客观的量化肢体肌肉疲劳的方法。我们将 进一步检查这些对肢体疲劳的影响是否部分归因于血流和氧气 (O2) 输送到四肢以及呼吸功和氧化应激如何影响它。在 健康受试者已被证明减少呼吸肌工作会增加血流量和氧气 输送至四肢。同样在健康受试者中，我们最近发现血流量 / O2 增加 传输到工作腿可显着减少肌肉疲劳并提高运动耐力。 此外，研究表明，氧化应激的减少也会增加血流量/氧气输送 然而，在老年健康个体的运动过程中，目前还没有关于氧化作用影响的数据。 COPD 患者运动期间肢体血流/O2 运输的压力。鉴于显着 运动期间所需的呼吸功增加，并且氧化应激显着增加 COPD患者，我们预计减少这些因素对肢体肌肉疲劳的影响的效果是 甚至比健康受试者还要高。我们认为这项研究将为以下方面提供新的有效方法： 通过让慢性阻塞性肺病患者在康复过程中提高运动能力 他们的运动肌肉的耐力。预计康复过程中的这一改进 将防止目前久坐慢性阻塞性肺病中普遍存在的肌肉功能恶化 人口。