The effect of higher ATP cost of contraction on the metabolic response to graded exercise in patients with chronic obstructive pulmonary disease

Abstract

To better understand the metabolic implications of a higher ATP cost of contraction in chronic obstructive pulmonary disease (COPD), we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine muscle energetics and pH in response to graded exercise. Specifically, in six patients and six well-matched healthy controls, we determined the intracellular threshold for pH (T(pH)) and inorganic phosphate-to-phosphocreatine ratio (T(Pi/PCr)) during progressive dynamic plantar flexion exercise with work rate expressed as both absolute and relative intensity. Patients with COPD displayed a lower peak power output (WRmax) compared with controls (controls 25 ᠴ W, COPD 15 ᠵ W, P = 0.01) while end-exercise pH (controls 6.79 ᠰ.15, COPD 6.76 ᠰ.21, P = 0.87) and PCr consumption (controls 82 ᠱ0%, COPD 70 ᠱ8%, P = 0.26) were similar between groups. Both T(pH) and T(Pi/PCr) occurred at a significantly lower absolute work rate in patients with COPD compared with controls (controls: 14.7 ᠲ.4 W for T(pH) and 15.3 ᠲ.4 W for T(Pi/PCr); COPD: 9.7 ᠴ.5 W for T(pH) and 10.0 ᠴ.6 W for T(Pi/PCr), P < 0.05), but these thresholds occurred at the same percentage of WRmax (controls: 63 ᠱ1% WRmax for T(pH) and 67 ᠱ8% WRmax for T(Pi/PCr); COPD: 59 ᠹ% WRmax for T(pH) and 61 ᠱ2% WRmax for T(Pi/PCr), P > 0.05). Indexes of mitochondrial function, the PCr recovery time constant (controls 42 ᠷ s, COPD 45 ᠱ1 s, P = 0.66) and the PCr resynthesis rate (controls 105 ᠲ1%/min, COPD 91 ᠳ1%/min, P = 0.43) were similar between groups. In combination, these results reveal that when energy demand is normalized to WRmax, as a consequence of higher ATP cost of contraction, patients with COPD display the same metabolic pattern as healthy subjects, suggesting that skeletal muscle energy production is well preserved in these patients.