Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

Gifford, Jayson R.; Trinity, Joel D.; Layec, Gwenael; Garten, Ryan S.; Park, Song-Young; Rossman, Matthew J.; Larsen, Steen; Dela, Flemming; Richardson, Russell S.

doi:10.1152/japplphysiol.00460.2015

Cited by 35 publications

(41 citation statements)

References 34 publications

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“…Quadriceps muscle citrate synthase activity, an index of mitochondrial capacity, was not different between controls and patients with COPD (Richardson et al 2004). Estimation of peak quadriceps muscle O 2 utilization (Gifford et al 2016), from in vitro mitochondrial respiration data, in patients with COPD is markedly greater (>0.40 l min −1 ) than theV MO 2 peak in the current patients with COPD (Gifford et al 2015(Gifford et al , 2017. Peak work load was 25% greater during KE in hyperoxia (100% O 2 ) compared to normoxia in patients with COPD (Richardson et al 1999).…”

Section: Muscle Diffusive O 2 Transportmentioning

confidence: 68%

Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs

Broxterman

Hoff

Wagner

et al. 2020

The Journal of Physiology

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Key pointsr Peak oxygen uptake, a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD), with mounting evidence supporting an important role for peripheral dysfunction, particularly within skeletal muscle.r In patients with severe COPD and activity-matched controls, muscle oxygen transport and utilization were assessed at peak effort during single-leg knee-extensor exercise (KE), where ventilation is assumed to be submaximal. This strategy removes ventilation as the major constraint to exercise capacity in COPD, allowing maximal muscle function to be attained and evaluated.r During maximal KE, both convective arterial oxygen delivery to the skeletal muscle microvasculature and subsequent diffusive oxygen delivery to the mitochondria were diminished in patients with COPD compared to control subjects.r These findings emphasize the importance of factors, beyond the lungs, that influence exercise capacity in this patient population and may, ultimately, influence the prognosis, mortality and quality of life for patients with COPD.Abstract Peak oxygen uptake (V O 2 peak ), a primary determinant of prognosis, mortality and quality of life, is diminished in patients with chronic obstructive pulmonary disease (COPD). Mounting evidence supports an important role of the periphery, particularly skeletal muscle, in the diminishedV O 2 peak with COPD. However, the peripheral determinants ofV O 2 peak have not been comprehensively assessed in this cohort. Thus, the hypothesis was tested that both muscle 600 R. M. Broxterman and others J Physiol 598.3convective and diffusive oxygen (O 2 ) transport, and therefore skeletal muscle peak O 2 uptake (V MO 2 peak ), are diminished in patients with COPD compared to matched healthy controls, even when ventilatory limitations (i.e. attainment of maximal ventilation) are minimized by using small muscle mass exercise. Muscle O 2 transport and utilization were assessed at peak exercise from femoral arterial and venous blood samples and leg blood flow (by thermodilution) in eight patients with severe COPD (forced expiratory volume in 1s (FEV 1 ) ± SEM = 0.9 ± 0.1 l, 30% of predicted) and eight controls during single-leg knee-extensor exercise. Both muscle convective O 2 delivery (0.44 ± 0.06 vs. 0.69 ± 0.07 l min −1 , P < 0.05) and muscle diffusive O 2 conductance (6.6 ± 0.8 vs. 10.4 ± 0.9 ml min −1 mmHg −1 , P < 0.05) were ß1/3 lower in patients with COPD than controls, resulting in an attenuatedV MO 2 peak in the patients (0.27 ± 0.04 vs. 0.42 ± 0.05 l min −1 , P < 0.05). When cardiopulmonary limitations to exercise are minimized, the convective and diffusive determinants ofV MO 2 peak , at the level of the skeletal muscle, are greatly attenuated in patients with COPD. These findings emphasize the importance of factors, beyond the lungs, that may ultimately influence this population's prognosis, mortality and quality of life.We are indebted to all of the participants for their time and effort expended to...

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Section: Muscle Diffusive O 2 Transportmentioning

confidence: 68%

Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs

Broxterman

Hoff

Wagner

et al. 2020

The Journal of Physiology

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“…Several studies found that sarcopenia is more common in patients with COPD than in matched healthy controls 69–71. In addition, adults with COPD exhibit skeletal muscle dysfunction at the biochemical, cellular, and structural levels 72,73. Finally, as the severity of COPD and the concomitant dyspnea worsens, patients can experience decrease in muscle strength, impaired mobility, sarcopenia, and ultimately, frailty.…”

Section: Sarcopeniamentioning

confidence: 99%

Frailty assessment in older adults with chronic obstructive respiratory diseases

Guan¹,

Huang²

2018

CIA

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The number of patients with chronic obstructive pulmonary disease (COPD) has been rising with continued exposure to environmental risk factors and aging of populations around the world. Frailty is a geriatric syndrome with a decline in physiological reserve and often coexists with chronic diseases such as COPD. Frailty is an independent risk factor for the development and progression of COPD, and COPD can lead to frailty; treating one might improve the other. Thus, there is an increasing interest in the assessment of frailty in patients with COPD. Furthermore, early identification and assessment of frailty in patients with COPD may affect the choice of intervention and improve its effectiveness. Based on the current literature, the intent of this review was to summarize and discuss frailty assessment tools used for COPD patients and the relevant clinical practices for predicting outcomes. We ascertain that using suitable frailty assessment tools could facilitate physicians to screen and stratify physically frail patients with COPD. Screening appropriately targeted population can achieve better intervention outcomes and pulmonary rehabilitation among frail COPD patients.

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“…Because of identical spectral characteristics, Hb and myoglobin (Mb) are not separated using NIRS. However, although still somewhat contentious (14), the signal is usually considered to be derived mainly from Hb (30). Changes in microvascular oxygenation of the calf muscle were continuously monitored at 2 Hz using a near infrared frequency resolved spectroscopy oximeter (Oxiplex TS; ISS, Champaign, IL).…”

Section: Subjectsmentioning

confidence: 99%

Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD

Layec

Hart

Trinity

et al. 2017

American Journal of Physiology-Endocrinology and Metabolism

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Patients with chronic obstructive pulmonary disease (COPD) experience a delayed recovery from skeletal muscle fatigue following exhaustive exercise that likely contributes to their progressive loss of mobility. As this phenomenon is not well understood, this study sought to examine postexercise peripheral oxygen (O) transport and muscle metabolism dynamics in patients with COPD, two important determinants of muscle recovery. Twenty-four subjects, 12 nonhypoxemic patients with COPD and 12 healthy subjects with a sedentary lifestyle, performed dynamic plantar flexion exercise at 40% of the maximal work rate (WR) with phosphorus magnetic resonance spectroscopy (P-MRS), near-infrared spectroscopy (NIRS), and vascular Doppler ultrasound assessments. The mean response time of limb blood flow at the offset of exercise was significantly prolonged in patients with COPD (controls: 56 ± 27 s; COPD: 120 ± 87 s; < 0.05). In contrast, the postexercise time constant for capillary blood flow was not significantly different between groups (controls: 49 ± 23 s; COPD: 51 ± 21 s; > 0.05). The initial postexercise convective O delivery (controls: 0.15 ± 0.06 l/min; COPD: 0.15 ± 0.06 l/min) and the corresponding oxidative adenosine triphosphate (ATP) demand (controls: 14 ± 6 mM/min; COPD: 14 ± 6 mM/min) in the calf were not significantly different between controls and patients with COPD ( > 0.05). The phosphocreatine resynthesis time constant (controls: 46 ± 20 s; COPD: 49 ± 21 s), peak mitochondrial phosphorylation rate, and initial proton efflux were also not significantly different between groups ( > 0.05). Therefore, despite perturbed peripheral hemodynamics, intracellular O availability, proton efflux, and aerobic metabolism recovery in the skeletal muscle of nonhypoxemic patients with COPD are preserved following plantar flexion exercise and thus are unlikely to contribute to the delayed recovery from exercise in this population.

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Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

Cited by 35 publications

References 34 publications

Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs

Determinants of the diminished exercise capacity in patients with chronic obstructive pulmonary disease: looking beyond the lungs

Frailty assessment in older adults with chronic obstructive respiratory diseases

Oxygen delivery and the restoration of the muscle energetic balance following exercise: implications for delayed muscle recovery in patients with COPD

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