Positives of negative work: Eccentric cycling effects on skeletal muscle in chronic obstructive pulmonary disease (COPD)

RATIONALE: Studies in healthy individuals have shown that for the same metabolic cost, significantly greater muscle forces are produced during negative (eccentric) compared to positive (concentric) work. Eccentric endurance cycle exercise has been proposed to enhance exercise capacity in patients with Chronic Obstructive Pulmonary Disease (COPD), particularly since they present with reduced muscle aerobic capacity and strength that relate to fiber atrophy and Type 2 fiber predominance. Given the stimulus-response relationship between the force of muscle contraction and degree of hypertrophy and strength development, eccentric endurance exercise may be expected to improve muscle mass and strength in COPD. The purpose of this study is to elucidate effects of eccentric endurance training on muscle structure, composition and function in moderate to severe COPD. METHODS: Three of 10 male (65±1.2 yrs) severe COPD patients (FEV1=37.7±2 %predicted) completed 10 weeks of eccentric cycle training. Pre and post testing included assessment of quadriceps muscle: 1) structure through needle biopsy to quantify fiber cross sectional area and type using immunofluorescent labeling of myosin-heavy chain Type 1 and 2 isoforms; 2) body composition using DEXA reflected as lean and fat tissue mass (kg); 3) muscle function determined by peak muscle strength and endurance (Nm) using the Biodex dynamometer. The muscle biopsy analyses were done with the investigator blinded to training status (pre versus post). RESULTS: As highlighted in Figure 1, cross-sectional area increased in Type 1 fibers by 76% (4570±1733 to 9048±3241μm2, p = 0.06), with little (7.6%) change in Type 2 fibers (5916±594 to 6221±979μm2) after training. The proportion of Type I fibers increased by 7% (28.6±6.6 to 36.1±21.5%) and Type 2 fibers decreased proportionally (71.4±6.6 to 63.9±21.5%). Thigh lean tissue mass increased (6.43±0.88 to 6.54±0.89kg, p<0.05) and fat mass decreased (2.82±0.65 vs. 2.68±0.59, p<0.05) after training. Endurance muscle power increased by 35% in two patients and there were no changes in peak isokinetic torque. CONCLUSION: These preliminary findings suggest eccentric cycling induces marked myofiber hypertrophy and shift specific to Type 1 fibers in COPD muscle, suggesting a relative lack of recruitment of Type 2 fibers during this exercise. These cellular changes are associated with improved lean and fat tissue mass of the thigh and improved muscular endurance. Taken together, eccentric cycling appears effective at inducing structural and functional adaptations within COPD muscle; however, completion of this ongoing randomized clinical trial is necessary to advance eccentric cycling as a novel training modality for COPD. (Figure Presented).