Is the Anaerobic Quadriceps Muscle Phenotype in Chronic Obstructive Pulmonary Disease Mediated by Reduced Muscle Concentrations of Peroxisome Proliferator-Activated Receptors Alpha and Delta?

Detailed Summary

Background Chronic Obstructive Pulmonary Disease (COPD) patients develop leg weakness and a reduced walking capacity, due to reduced leg muscle oxygen-utilising capacity (OUC). Animal experiments indicate that low muscle levels of Peroxisome Proliferator-Activated Receptors (PPAR) cause the reduced muscle OUC. Aims In COPD patients, investigate whether: 1. reduced muscle PPAR levels cause reduced leg muscle OUC, by investigating a correlation between these in muscle samples (Study 1). 2. training increases muscle PPAR levels in proportion to increases in OUC, as should occur if PPARs control OUC (Study 2). 3. muscle PPAR levels and walking capacity correlate (Study 1 and 2). 3\. the new technique of repetitive stimulation of the nerve to the leg with a magnet (rMS) improves muscle OUC (Study 2). Study 1 Leg weakness and walking ability are assessed in 75 patients, then a leg muscle sample is taken to measure PPARs and OUC. Study 2 60 Study 1 patients have either cardiovascular training, rMS, or no training, for 8 weeks, then are re-studied as in Study 1. Importance If reduced PPAR levels correspond with leg weakness, medicines can be developed to target these receptors and treat weakness. If rMS is effective, it can be offered to patients.

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