Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: preliminary findings

Abstract

Layec G, Haseler LJ, Hoff J, Richardson RS. Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: preliminary findings. Am J Physiol Regul Integr Comp Physiol 300: R1142-R1147, 2011. First published February 9, 2011 doi:10.1152/ajpregu.00835.2010.-Impaired metabolism in peripheral skeletal muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We used 31 P-magnetic resonance spectroscopy ( 31 P-MRS) to examine the energy cost and skeletal muscle energetics in six patients with COPD during dynamic plantar flexion exercise compared with six well-matched healthy control subjects. Patients with COPD displayed a higher energy cost of muscle contraction compared with the controls (control: 6.1 Ϯ 3.1% of rest·min Ϫ1 ·W Ϫ1 , COPD: 13.6 Ϯ 8.3% of rest·min Ϫ1 ·W Ϫ1 , P ϭ 0.01). Although, the initial phosphocreatine resynthesis rate was also significantly attenuated in patients with COPD compared with controls (control: 74 Ϯ 17% of rest/min, COPD: 52 Ϯ 13% of rest/min, P ϭ 0.04), when scaled to power output, oxidative ATP synthesis was similar between groups (6.5 Ϯ 2.3% of rest·min Ϫ1 ·W Ϫ1 in control and 7.8 Ϯ 3.9% of rest·min Ϫ1 ·W Ϫ1 in COPD, P ϭ 0.52). Therefore, our results reveal, for the first time that in a small subset of patients with COPD a higher ATP cost of muscle contraction may substantially contribute to the lower mechanical efficiency previously reported in this population. In addition, it appears that some patients with COPD have preserved mitochondrial function and normal energy supply in lower limb skeletal muscle. 31 P-MRS; muscle metabolism; exercise; mitochondrial function LIMITED EXERCISE CAPACITY not only plays a central role in the life of patients with chronic obstructive pulmonary disease (COPD), but also acts both as a marker of well-being and a prognostic tool. Given that COPD is a disease of the lung, it has long been proposed that the inability to sustain a high level of ventilation was the main factor that limited exercise performance in these patients (3). However, as leg discomfort was a frequent exercise-limiting symptom invoked by patients with COPD during cycling exercise (15), peripheral muscle dysfunction has also been implicated (19). To date, the mechanistic basis for this exercise intolerance is still unresolved (6, 22), although a decrease in muscle strength and endurance along with reduced capillarization, percentage of oxidative fibers, and a reduced activity of different oxidative enzymes measured in vitro may play a role.These biochemical and histochemical changes observed in the peripheral skeletal muscle of patients with COPD (32) likely alter muscle energy production during exercise and recovery, which may, in turn, affect exercise capacity. Previously, a decreased mechanical efficiency (the chemical conversion of energy to mechanical work) has been reported in a small subset of patients with COPD (1, 25). In these studies, such a decrease in mechanical...

In vivoevidence of an age-related increase in ATP cost of contraction in the plantar flexor muscles

“…It is noteworthy that the increased ATP cost of contraction observed in the present study is of far greater magnitude than the alterations in the metabolic cost of locomotion (∼ 20-30 %). However, changes of similar magnitude have been reported previously in the plantar flexor muscles of patients with chronic heart failure [39] and COPD (chronic obstructive pulmonary disease) [40,41], which have also been related to whole-body O 2 cost during cycling [42]. When the ATP cost of contraction from the young and old subjects were combined in the present study, we calculated a coefficient of variation of 82 %.…”

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

“…The change in fiber type profile in COPD muscle may explain low mechanical efficiency in these patients (203). This finding is supported by a study demonstrating higher ATP consumption for a given mechanical work rate in patients with COPD (204). Measurements of resting and total whole-body energy expenditure also support higher energy requirements of patients with COPD (205,206).…”

Nutritional assessment and therapy in COPD: a European Respiratory Society statement

“…Moreover, while the normal response to semi-starvation is a reduced metabolic rate and depressed whole-body protein turnover, weight-losing COPD patients may display elevated resting energy expenditure and increased whole-body protein turnover [27]. Furthermore, in addition to an increased cost of ventilation due to abnormal pulmonary mechanics, a higher ATP cost of muscular contraction [28] may contribute to decreased mechanical efficiency of lower limb exercise [29] and elevated daily energy requirements in some COPD patients [30]. In support of this, weight gain after lung volume reduction surgery was associated with improved lung function and reduced work of breathing [31].…”