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

主要研究者（末次，首次）：Amann，Markus 摘要 COPD患者的日常活动受到限制，因为运动受限， 严重到妨碍简单的日常工作。这项拟议中的研究将研究可能 有助于这种严重限制运动耐量，也决定如何运动耐量可能是 提高具体来说，我们将评估过度呼吸肌工作的作用， COPD患者，以及该人群运动期间氧化应激升高。此外，我们将评估 呼吸功的增加是否是氧化水平增加的重要因素， COPD患者运动时的应激反应。我们将a）使用机械呼吸机结合 降低密度的气体混合物，以减少循环运动期间的呼吸功，以及B）使用静脉 在循环运动中输注维生素C，以检查两者的影响，减少呼吸工作， 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， 提供一种灵敏的、可重复的、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拟议影响是否部分归因于血流和氧气 (O2)运输到四肢，以及这是如何受到呼吸和氧化应激的影响。在 健康的受试者已经表明，呼吸肌功的减少会增加血流量和O2 运输到四肢。此外，在健康受试者中，我们最近发现，血流量/ O2增加 运输到工作腿显著地减少肌肉疲劳并提高运动耐量。 此外，已经表明，氧化应激的减少也增加了血流量/ O2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应激的影响的数据。 COPD患者运动时肢体血流/氧转运负荷鉴于重大的 运动期间所需的呼吸功增加， 对于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 甚至比健康受试者更高。我们认为，这项研究将提供新的有效方法， 通过让COPD患者改善来提高他们在康复期间的运动能力 运动肌肉的耐力。预计恢复进程的这一改善 将防止目前在久坐的COPD患者中普遍存在的肌肉功能的恶化 人口

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.