Determinants of skeletal muscle work efficiency in patients with COPD

Abstract

Skeletal muscle work inefficiency plays a major role in limiting exercise capacity in patients with chronic Obstructive Pulmonary Disease (COPD). However, the physiological mechanisms responsible for this excessive energy demand from the exercising muscle of patients with COPD remains poorly understood. To address this gap in our knowledge, we measured the cost of muscle contraction (ATP cost) in the quadriceps of patients with moderate to severe COPD (n=11) and age‐matched sedentary controls (n=12) with phosphorus magnetic resonance spectroscopy (31P‐MRS) during 1) maximal intermittent contractions to elicit a metabolic demand from both cross‐bridge cycling and ion pumping and 2) a continuous maximal contraction to predominantly tax cross‐bridge cycling. In addition, muscle fiber type distribution was determined in the vastus lateralis using immunofluorescence analysis. The ATP cost of contraction for both the continuous (Control: 0.11 ± 0.07 mM.min−1.N m−1; COPD: 0.12 ± 0.07 mM.min−1.N m−1) and intermittent (Control: 0.24 ± 0.17 mM.min−1.N m−1; COPD: 0.24 ± 0.18 mM.min−1.N m−1) protocols were not significantly different between groups with or without normalization for muscle mass (P>0.05). Somewhat surprisingly, fiber type distribution was also not different between groups (Type I; Control: 41 ± 12 %; COPD: 40 ± 18 %; Type II; Control: 59 ± 12 %; COPD: 60 ± 18 % respectively P>0.05). Of note, this finding of similar fiber type composition in controls and COPD was partly the consequence of a relatively high proportion of type II fibers in the elderly controls. These, somewhat serendipitous, data reveal that excessive energy demand from ion pumping or myosin ATPase per se is not an obligatory component of the skeletal muscle work inefficiency in COPD and suggest that the previously documented elevated ATP cost of contraction in the locomotor muscles of these patients was likely mediated by a fiber type shift. In practical terms, these findings highlight the potential importance of developing effective therapeutic strategies to limit the likely deleterious consequences of a skeletal muscle fiber type shift in the lower limbs of patients with COPD.Support or Funding InformationThis work was funded in part by grants from the Flight Attendant Medical Research Institute (FAMRI), NIH National Heart, Lung, and Blood Institute (PO1 HL 091830, K99HL125756) and VA Merit grant E6910R.