Skeletal and respiratory muscle dysfunction in patients with COPD: the role of sympathetic activation

• Applicant: Professor Dr. Tobias Raupach
• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 144099232

Exercise intolerance, skeletal muscle dysfunction and reduced daily activity are central in COPD patients and closely relate to quality of life and prognosis. Molecular, cellular and functional alterations occur in skeletal muscle and the diaphragm in COPD. Studies assessing muscle exercise in animal models as well as in healthy subjects and patients with heart failure have revealed that muscle dysfunction leads to a more pronounced activation of muscle afferents at rest and particularly during exercise. This ergoreflex is mediated by increased sympathetic outflow and contributes to muscle hypoperfusion, increased respiratory drive and dyspnoea during exercise. We and others recently found striking neurohumoral activation in COPD patients. The objective of this project is to study the causes of exercise limitation, dyspnea and neurohumoral activation in COPD. The principal hypothesis Is that In patients suffering from COPD, resting MSNA correlates with the ventilatory equivalent ratio, dyspnea and exercise limitation. In addition, handgrip exercise further increases MSNA whereas resistive unloading by non-invasive ventilation (NIV) leads to a decrease in clinical symptoms and sympathetic activation. These effects are expected to be greater in patients as compared to matched healthy controls. Participants will undergo symptom limited bicycle exercise and a handgrip protocol. Patients on NIV will undergo the same study protocol with and without NIV use. Sympathovagal balance will be assessed by microneurography recordings and baroreflexes.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Stefan Andreas