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（最后，第一个）：阿曼，马库斯 抽象的 COPD患者的日常活动受到限制，因为运动限制可以充分 严重损害简单的日常任务。拟议的研究将研究可能的新机制 有助于这种严重的运动耐受性，还确定运动能力的可能性 改进。具体而言，我们将评估过度呼吸道肌肉工作的作用，这是 COPD患者在该人群中运动过程中氧化应激升高。此外，我们将评估 呼吸的增加是否是氧化水平升高的重要原因 COPD患者运动过程中的压力。我们将a）使用机械呼吸机与 降低密度气体混合物以减少周期练习期间呼吸的工作，b）使用静脉 在周期运动过程中注入维生素C，以检查两者的影响，呼吸的工作减少和 锻炼腿部肌肉疲劳的氧化应激减少。我们将使用一种新颖的组合 提供敏感，可重复的客观，量化肢体肌肉疲劳的方法。我们将 进一步检查这些提出对肢体疲劳的影响是否部分是由于血流和氧气引起的 （O2）运输到四肢，以及这如何受到呼吸和氧化应激的工作的影响。在 健康受试者已经表明，呼吸肌肉工作的减少会增加血流，而O2 运输到四肢。同样在健康受试者中，我们最近透露，血流 / O2的增加 运输到工作腿可显着减轻肌肉疲劳并提高运动耐受性。 此外，已经表明氧化应激的减少也增加了血流 / O2的递送 但是，在老年健康个体的运动中，目前尚无有关氧化作用的数据 运动过程中COPD患者的肢体流量 / O2转运的压力。鉴于显着 运动过程中需要增加的呼吸工作，并大大增加氧化应激 COPD患者，我们期望减少这些因素对肢体肌肉疲劳的影响会产生的影响 甚至比健康的受试者大。我们建议这项研究将提供新的有效方法 通过允许他们改善COPD患者的康复期间，提高运动能力 他们的运动肌肉的耐力。预计康复过程的这种改善 将防止目前在久坐的COPD中普遍存在的肌肉功能的恶化 人口。