Mitochondrial membrane potential in the airway and skeletal muscle compartments of smokers with and without COPD

Introduction & Rationale COPD is a disease of the airways and lungs with extra pulmonary manifestations. Mitochondria are important in the pathways that prevent the ageing process and oxidative stress. If oxidative stress arose from the lung and spilled over to cause skeletal muscle weakness then greater evidence of mitochondrial dysfunction should be evident in the lung. Objectives We measured mitochondrial membrane potential (ΔYm) as a marker of mitochondrial dysfunction in endobronchial and skeletal muscle biopsies from COPD patients and healthy smokers matched for smoking history, age and sex. Methods and Measurement We have biopsied 6 GOLD II, 2 GOLD I (COPD) and 6 Healthy smokers. Endobronchial biopsy and percutaneous muscle biopsy of the vastus lateralis were obtained on the same day; additional phenotypic measurements included lung function, incremental exercise test, 6-minute walk (6MW) distance and CT thorax. Mitochondria were isolated from tissue and ΔYm measured using the carbocyanine dye JC-1. Results Results Mean±SEM Healthy (n=6) GOLDI (n=2) GOLDII (n=6) Age (years) 64±2 60±3 64±1 Smoking (Pack-Years) 34±5 38±2 36±6 FEV1 (% predicted) 103±5 92±3 72±2* 6MW (m) 633±32 618±73 503±27* VO2 peak (ml/min/kg) 26±2 24±1 17±1* Airway membrane potential (units) 18.0±2.1 19.6±2.7 11.3±1.5* Muscle membrane potential (units) 4.3±0.9 4.3±1.1 4.9±0.7 Conclusion Of the 6 GOLD II patients 2 had emphysema on CT, interestingly so did both the GOLD I patients. GOLD II patients had a significantly lower ΔYm in the airways compared to healthy smokers (P=0.035). No such difference is demonstrated in the muscle thus supporting the spill over hypothesis.