Abstract
Background: Oxidative/carbonyl stress is elevated in lower-limb muscles of patients with Chronic Obstructive Pulmonary Disease (COPD). Carnosine is a skeletal muscle antioxidant particularly present in fast-twitch fibers. Aims: To compare muscle carnosine, oxidative/carbonyl stress, antioxidants and fiber characteristics between patients with COPD and healthy controls (HCs), and between patients after stratification for airflow limitation (mild/moderate vs. severe/very-severe). To investigate correlates of carnosine in patients with COPD. Methods: A vastus lateralis muscle biopsy was obtained from 40 patients with stable COPD and 20 age/sex matched HCs. Carnosine, oxidative/carbonyl stress, antioxidants, fiber characteristics, quadriceps strength and endurance (QE), VO 2 peak (incremental cycle test) and physical activity (PA) were determined. Results: Patients with COPD had a similar carnosine concentration (4.16 mmol/kg wet weight (WW) (SD 1.93)) to HCs (4.64 mmol/kgWW (SD 1.71)) and significantly higher percentage of fast-twitch fibers and lower QE, VO 2 peak and PA vs. HCs. Patients with severe/very-severe COPD had a 30% lower carnosine concentration (3.24 mmol/kgWW (SD 1.79); n=15) vs. patients with mild/moderate COPD (4.71 mmol/kgWW (SD 1.83); n=25; P=0.02) and significantly lower VO 2 peak and PA vs. patients with mild/moderate COPD. Carnosine correlated significantly with QE (r s =0.427), VO 2 peak (r s =0.334), PA (r s =0.379) and lung function parameters in patients with COPD. Conclusion: Despite having the highest proportion of fast-twitch fibers, patients with severe/very-severe COPD displayed a 30% lower muscle carnosine concentration compared to patients with mild/moderate COPD. As no oxidative/carbonyl stress markers, nor antioxidants were affected, the observed carnosine deficiency is thought to be a possible first sign of muscle redox balance abnormalities.