Respiratory Muscle Dysfunction in COPD: From Muscle to Cell
Respiratory muscle dysfunction is a cardinal feature of acute and chronic respiratory failure in COPD. Diaphragm and accessory inspiratory muscles face increased load due to increased lung resistance and elastance, as well as increased ventilatory demands. Concomitantly, the capacity of the inspiratory muscles to generate pressure is decreased due to mechanical disadvantage imposed by hyperinflation. Additionally, inflammation and oxidative stress impair muscle fiber specific force generation and increase diaphragm susceptibility to sarcomere disruption during acute inspiratory loading. In response to this increased load, diaphragm presents unique adaptations in its cellular structure and passive and contractile mechanical properties, and displays a more efficient metabolic armamentarium. A shift of muscle fiber type towards slow-twitch, oxidative type I fibers, which are more fatigue-resistant, increases diaphragmatic endurance but protein degradation and a significant reduction in myosin content decrease its force generating capacity. Furthermore, diaphragm adapts to chronic hyperinflation by sarcomere deletion so that its overall length is shortened, in an attempt to preserve optimum force-length relationship. Adaptation however may not be complete, or may be overwhelmed by pathophysiologic derangements during exercise or acute exacerbations, leading to obvious “dysfunction” of the respiratory muscles, and if sustained, ultimately to muscle fatigue and respiratory pump failure.
No Supplementary Data
No Article Media
Document Type: Research Article
Publication date: 01 April 2011
More about this publication?
- Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.