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

首席调查员(最后一个，第一个)：阿曼，马库斯 摘要 慢性阻塞性肺疾病患者的日常活动受到限制，因为运动受限。 严重损害简单的日常任务。这项拟议的研究将检验可能 造成运动耐量的严重限制，也决定了运动耐量可能有多大 改进了。具体地说，我们将评估过度呼吸肌工作的作用，这是 COPD患者，以及这一人群在运动期间氧化应激增加。此外，我们还将评估 呼吸功的增加是否是提高氧化水平的重要因素 慢性阻塞性肺疾病患者运动时的应激反应。我们将a)结合使用机械呼吸机和 降低密度的气体混合物，以减少自行车运动中的呼吸功和b)使用静脉 在自行车运动中注射维生素C以检查两者的效果，呼吸和运动的功减少 减少氧化应激对运动腿肌肉疲劳的影响。我们将使用一种新颖的组合 方法提供一种灵敏的、可重复性的、客观的四肢肌肉疲劳量化方法。我们会 进一步研究这些对肢体疲劳的影响是否部分归因于血液流动和氧气。 (O2)运输到四肢，以及呼吸和氧化应激对此有何影响。在……里面 健康受试者已经表明，呼吸肌作功的减少会增加血流量和氧气 运往四肢。同样在健康的受试者中，我们最近发现血液流量/O2的增加 运送到工作腿上可以显著减少肌肉疲劳，提高运动耐力。 此外，研究还表明，氧化应激的减少也会增加血流量/氧气输送。 然而，在老年健康人的锻炼过程中，目前还没有关于氧化影响的数据 运动应激对慢性阻塞性肺疾病患者肢体血流量/氧转运的影响鉴于重要的是 运动中需要增加的呼吸功和显著增加的氧化应激 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 甚至比健康受试者还要大。我们认为，这项研究将提供新的有效方法 提高慢性阻塞性肺疾病患者康复期间的运动能力 他们运动肌肉的耐力。预计康复进程的这一改进 将防止目前久坐不动的COPD患者普遍存在的肌肉功能恶化 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.