Myoglobin Content in Leg Skeletal Muscle in Patients with Chronic Obstructive Lung Disease

Möller, Peter; Hellström, Kjell; Hermansson, I

doi:10.1159/000194594

Cited by 5 publications

(4 citation statements)

References 11 publications

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“…Myoglobin has been suggested to be important in O 2 transport from blood to muscle cells (49) and has previously been reported to be reduced in patients with COPD (50). The current data ( Table 2) are at the high end of the range of myoglobin concentration previously reported in humans of 4 to 8 mg/g of wet muscle (50, 51) but were not different between control subjects and patients.…”

Section: O 2 Transport and V Osupporting

confidence: 56%

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise

Richardson

Leek

Gavin

et al. 2004

Am J Respir Crit Care Med

154

168

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We studied six patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 1.1 +/- 0.2 L, 32% of predicted) and six age- and activity level-matched control subjects while performing both maximal bicycle exercise and single leg knee-extensor exercise. Arterial and femoral venous blood sampling, thermodilution blood flow measurements, and needle biopsies allowed the assessment of muscle oxygen supply, utilization, and structure. Maximal work rates and single leg VO2max (control subjects = 0.63 +/- 0.1; patients with COPD = 0.37 +/- 0.1 L/minute) were significantly greater in the control group during bicycle exercise. During knee-extensor exercise this difference in VO2max disappeared, whereas maximal work capacity was reduced (flywheel resistance: control subjects = 923 +/- 198; patients with COPD = 612 +/- 81 g) revealing a significantly reduced mechanical efficiency (work per unit oxygen consumed) with COPD. The patients had an elevated number of less efficient type II muscle fibers, whereas muscle fiber cross-sectional areas, capillarity, and mitochondrial volume density were not different between the groups. Therefore, although metabolic capacity per se is unchanged, fiber type differences associated with COPD may account for the reduced muscular mechanical efficiency that becomes clearly apparent during knee-extensor exercise, when muscle function is no longer overshadowed by the decrement in lung function.

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Section: O 2 Transport and V Osupporting

confidence: 56%

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise

Richardson

Leek

Gavin

et al. 2004

Am J Respir Crit Care Med

154

168

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“…The normobaric hypoxia models in this study showed a reduction of myoglobin levels in limb muscles, recapitulating the condition in COPD patients 23 . Myoglobin plays a crucial role in oxygen storage, buffering, and diffusion within myofibres (S21).…”

Section: Discussionsupporting

confidence: 54%

“…The normobaric hypoxia models in this study showed a reduction of myoglobin levels in limb muscles, recapitulating the condition in COPD patients. 23 Myoglobin plays a crucial role in oxygen storage, buffering, and diffusion within myofibres (S21). Its reduction implies that chronic hypoxia not only affects oxygen supply but also diminishes oxygen transport and storage capacities in skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Chronic hypoxia impairs skeletal muscle repair via HIF‐2α stabilization

Yin,

Fu,

Elengickal

et al. 2024

J cachexia sarcopenia muscle

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BackgroundChronic hypoxia and skeletal muscle atrophy commonly coexist in patients with COPD and CHF, yet the underlying physio‐pathological mechanisms remain elusive. Muscle regeneration, driven by muscle stem cells (MuSCs), holds therapeutic potential for mitigating muscle atrophy. This study endeavours to investigate the influence of chronic hypoxia on muscle regeneration, unravel key molecular mechanisms, and explore potential therapeutic interventions.MethodsExperimental mice were exposed to prolonged normobaric hypoxic air (15% pO2, 1 atm, 2 weeks) to establish a chronic hypoxia model. The impact of chronic hypoxia on body composition, muscle mass, muscle strength, and the expression levels of hypoxia‐inducible factors HIF‐1α and HIF‐2α in MuSC was examined. The influence of chronic hypoxia on muscle regeneration, MuSC proliferation, and the recovery of muscle mass and strength following cardiotoxin‐induced injury were assessed. The muscle regeneration capacities under chronic hypoxia were compared between wildtype mice, MuSC‐specific HIF‐2α knockout mice, and mice treated with HIF‐2α inhibitor PT2385, and angiotensin converting enzyme (ACE) inhibitor lisinopril. Transcriptomic analysis was performed to identify hypoxia‐ and HIF‐2α‐dependent molecular mechanisms. Statistical significance was determined using analysis of variance (ANOVA) and Mann–Whitney U tests.ResultsChronic hypoxia led to limb muscle atrophy (EDL: 17.7%, P < 0.001; Soleus: 11.5% reduction in weight, P < 0.001) and weakness (10.0% reduction in peak‐isometric torque, P < 0.001), along with impaired muscle regeneration characterized by diminished myofibre cross‐sectional areas, increased fibrosis (P < 0.001), and incomplete strength recovery (92.3% of pre‐injury levels, P < 0.05). HIF‐2α stabilization in MuSC under chronic hypoxia hindered MuSC proliferation (26.1% reduction of MuSC at 10 dpi, P < 0.01). HIF‐2α ablation in MuSC mitigated the adverse effects of chronic hypoxia on muscle regeneration and MuSC proliferation (30.9% increase in MuSC numbers at 10 dpi, P < 0.01), while HIF‐1α ablation did not have the same effect. HIF‐2α stabilization under chronic hypoxia led to elevated local ACE, a novel direct target of HIF‐2α. Notably, pharmacological interventions with PT2385 or lisinopril enhanced muscle regeneration under chronic hypoxia (PT2385: 81.3% increase, P < 0.001; lisinopril: 34.6% increase in MuSC numbers at 10 dpi, P < 0.05), suggesting their therapeutic potential for alleviating chronic hypoxia‐associated muscle atrophy.ConclusionsChronic hypoxia detrimentally affects skeletal muscle regeneration by stabilizing HIF‐2α in MuSC and thereby diminishing MuSC proliferation. HIF‐2α increases local ACE levels in skeletal muscle, contributing to hypoxia‐induced regenerative deficits. Administration of HIF‐2α or ACE inhibitors may prove beneficial to ameliorate chronic hypoxia‐associated muscle atrophy and weakness by improving muscle regeneration under chronic hypoxia.

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“…Another indicator for impaired oxidative muscle metabolism in COPD is the slow phosphocreatine resynthesis rate at the end of exercise, which is closely related to adenosine triphosphate resynthesis and thus energy restoration [16,17,21]. Moreover, besides the limited oxygen uptake, delivery of oxygen to the peripheral muscles also seems to be impaired, probably as a result of reduced capillarity and low levels of myoglobin, which has a key role in the transport and storage of oxygen [22]. …”

Section: Peripheral Muscle Dysfunction In Copdmentioning

confidence: 99%

The Potential Anti-Inflammatory Effect of Exercise in Chronic Obstructive Pulmonary Disease

Vlist¹,

Janssen²

2009

Respiration

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People with chronic obstructive pulmonary disease (COPD) suffer from muscle dysfunction which seems to be partly caused by systemic inflammation. Muscle protein breakdown as well as synthesis might be affected by this systemic inflammation. Additionally, it seems to induce excessive oxidative stress and reduce the level of growth-stimulating factors. As exercise training can have an anti-inflammatory effect in healthy people, the main question in this review is whether exercise (training) can also induce such effects in patients with COPD. However, because of the known inflammatory response after an acute bout of exercise, some researchers are afraid that exercise might actually worsen the inflammation in COPD. Recent evidence suggests, however, that the response might actually be anti-inflammatory and thus beneficial. Unfortunately, the evidence about the response of the inflammatory cytokines tumor necrosis factor-α and interleukin-6 to exercise in patients with COPD is inconsistent, making it impossible to conclude whether a single exercise bout is harmful or beneficial in patients with COPD. Long-term exercise training in healthy people as well as in patients with chronic heart failure, another chronic inflammatory disease, seems to have beneficial effects on the inflammatory response. In patients with COPD, however, no training-induced changes in cytokine levels have been found and it must be concluded that physical exercise training does not seem to have an anti-inflammatory effect in COPD. On the other hand, it does not have a proinflammatory effect, and since patients with COPD benefit from exercise training with regard to other health parameters it is still recommended that they exercise regularly.

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Myoglobin Content in Leg Skeletal Muscle in Patients with Chronic Obstructive Lung Disease

Cited by 5 publications

References 11 publications

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise

Chronic hypoxia impairs skeletal muscle repair via HIF‐2α stabilization

The Potential Anti-Inflammatory Effect of Exercise in Chronic Obstructive Pulmonary Disease

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Myoglobin Content in Leg Skeletal Muscle in Patients with Chronic Obstructive Lung Disease

Cited by 5 publications

References 11 publications

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o2with Small Muscle Mass Exercise

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o2with Small Muscle Mass Exercise

Chronic hypoxia impairs skeletal muscle repair via HIF‐2α stabilization

The Potential Anti-Inflammatory Effect of Exercise in Chronic Obstructive Pulmonary Disease

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Product

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Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise

Reduced Mechanical Efficiency in Chronic Obstructive Pulmonary Disease but Normal Peak V̇o₂with Small Muscle Mass Exercise