Respiratory muscle work and oxidative stress in COPD: impact on leg blood flow an

描述（由申请人提供）：COPD患者的日常活动受到限制，因为运动限制可能严重到足以损害简单的日常任务。这项研究将研究可能导致运动耐量严重限制的新机制，并确定如何提高运动耐量。具体而言，我们将评估过度呼吸肌工作的作用，COPD患者的特征，以及运动期间氧化应激升高在这一人群中的作用。此外，我们将评估呼吸功的增加是否是COPD患者运动期间氧化应激水平增加的重要因素。我们将a）使用机械呼吸机结合低密度气体混合物，以减少循环运动期间的呼吸功，以及B）在循环运动期间使用维生素C的静脉输注，以检查两者的影响，减少呼吸功和减少运动腿部肌肉疲劳的氧化应激。我们将使用一种新的方法组合，以提供一个灵敏的，可重复的，客观的手段量化肢体肌肉疲劳。我们将进一步研究这些对肢体疲劳的影响是否部分是由于血液流动和氧气（O2）运输到肢体以及呼吸和氧化应激的影响。在健康受试者中，已经表明呼吸肌功的减少增加了血液流量和向四肢的O2运输。此外，在健康受试者中，我们最近发现，增加血流量/ O2运输到工作腿显着减少肌肉疲劳，提高运动耐力。此外，已经表明，在老年健康个体中，氧化应激的减少也会增加运动期间的血流量/ O2输送，然而，目前还没有关于氧化应激对COPD患者运动期间肢体血流量/ O2运输的影响的数据。考虑到COPD患者在运动期间所需的呼吸功显著增加以及氧化应激显著增加，我们预计减少这些因素对肢体肌肉疲劳的影响的效果甚至比健康受试者更大。我们建议，这项研究将提供新的有效方法，以提高运动能力，在康复过程中的COPD患者，让他们提高他们的运动肌肉的耐力。预计康复过程中的这种改善将防止目前在久坐COPD人群中普遍存在的肌肉功能恶化。 公共卫生相关性：我们建议，这项研究将提供新的有效方法，以提高运动能力，在康复过程中的COPD患者，让他们提高耐力，他们的运动（腿）肌肉。预计康复过程中的这种改善将防止目前在久坐COPD人群中普遍存在的肌肉功能恶化。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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 (leg) 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.