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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

基本信息

批准号：
8598651
负责人：
MARKUS AMANN
金额：
$ 24.85万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
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/8598651
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 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

项目摘要

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）：Amann, Markus