The muscle hypothesis revisited

Coats, Andrew J.S.

doi:10.1002/ejhf.918

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…Thus, repetitions of aspiration pneumonia may induce further muscle atrophy. A previous study presented a muscle hypothesis in which alterations of skeletal muscle structure and function lead to overactive ergoreflex, which exaggerates the hemodynamics, ventilatory effects, and symptomatic dyspnea . Similarly, we suggest that the systemic consequence of skeletal muscle loss in aspiration pneumonia is a vicious cycle of repeating onsets of aspiration pneumonia and further muscle atrophy.…”

Section: Discussionsupporting

confidence: 59%

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

Komatsu

Okazaki

Ebihara

et al. 2018

J cachexia sarcopenia muscle

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BackgroundRepetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase‐3, followed by further degradation by the ubiquitin‐proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms.MethodsWe employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra‐nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real‐time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients.ResultsThe aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase‐3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin‐proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients.ConclusionsAspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis‐swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.

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Section: Discussionsupporting

confidence: 59%

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

Komatsu

Okazaki

Ebihara

et al. 2018

J cachexia sarcopenia muscle

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“…More interestingly, the increased expression of HIF-1α was found to be positively correlated with the absolute capillary-to-fibre ratio in the skeletal muscles of HF patients post-training. Overall, we speculate that the elevated expression levels of HIF-1α in skeletal muscles of HF patients post-training might indicate the exercise training-induced stimulation of muscle angiogenic adaptations (capillarization), possibly due to skeletal muscle ischemia that may persist during exercise in this clinical population typically characterized by peripheral myopathy [4].…”

Section: Discussionmentioning

confidence: 93%

“…Indeed, reduced exercise capacity, which is a hallmark of HF and has been associated with poor prognosis, cannot be fully explained by the decrease of left ventricular ejection fraction (LVEF) in these patients [2,3]. These observations further support the importance of muscle hypothesis in HF-related exercise intolerance [4,5].…”

Section: Introductionmentioning

confidence: 92%

Exercise Training Enhances Angiogenesis-Related Gene Responses in Skeletal Muscle of Patients with Chronic Heart Failure

Tryfonos

Tzanis

Pitsolis

et al. 2021

Cells

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Peripheral myopathy consists of a hallmark of heart failure (HF). Exercise enhanced skeletal muscle angiogenesis, and thus, it can be further beneficial towards the HF-induced myopathy. However, there is limited evidence regarding the exercise type that elicits optimum angiogenic responses of skeletal muscle in HF patients. This study aimed to (a) compare the effects of a high-intensity-interval-training (HIIT) or combined HIIT with strength training (COM) exercise protocol on the expression of angiogenesis-related factors in skeletal muscle of HF patients, and (b) examine the potential associations between the expression of those genes and capillarization in the trained muscles. Thirteen male patients with chronic HF (age: 51 ± 13 y; BMI: 27 ± 4 kg/m2) were randomly assigned to a 3-month exercise program that consisted of either HIIT (N = 6) or COM training (N = 7). Vastus lateralis muscle biopsies were performed pre- and post-training. RT-PCR was used to quantify the fold changes in mRNA expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR-2), hypoxia-inducible factor 1 alpha (HIF-1α), angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2), angiopoietin receptor (Tie2), and matrix metallopeptidase 9 (MMP-9), and immunohistochemistry to assess capillarization in skeletal muscle post-training. There was an overall increase in the expression levels of VEGF, VEGFR-2, HIF-1α, Ang2, and MMP9 post-training, while these changes were not different among groups. Changes in capillary-to-fibre ratio were found to be strongly associated with Tie2 and HIF-1α expression. This was the first study demonstrating that both HIIT and combined HIIT with strength training enhanced similarly the expression profile of angiogenic factors in skeletal muscle of HF patients, possibly driving the angiogenic program in the trained muscles, although those gene expression increases were found to be only partially related with muscle capillarization.

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“…These symptoms, however, cannot be totally attributed to central cardiovascular alterations. There are peripheral mechanisms that contribute to the symptoms' appearance and persistence, and make up HF-related skeletal myopathy [66][67][68][69] including, among other factors, changes in the percentage of type I (oxidative, slow-twitch) and type IIb (glycolytic, fast-twitch) muscle fibers; reduced capillary density; decreased muscle metabolism, with rapid depletion of high-energy phosphates and rapid decline in muscle pH on exercise; lower mitochondrial density and mitochondrial oxidative enzyme activity; and muscle atrophy [66].…”

Section: Discussionmentioning

confidence: 99%

Prevalence and impact of sarcopenia in individuals with heart failure with reduced ejection fraction (the SARC-HF study): A prospective observational study protocol

Nascimento,

Rodrigues Junior,

Felix Mediano

et al. 2024

PLoS ONE

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Sarcopenia, a clinical syndrome primarily associated with reduced muscle mass in the elderly, has a negative impact on quality of life and survival. It can occur secondarily to other diseases such as heart failure (HF), a complex clinical syndrome with high morbidity and mortality. The simultaneous occurrence of these two conditions can worsen the prognosis of their carriers, especially in the most severe cases of HF, as in patients with reduced left ventricular ejection fraction (LVEF). However, due to the heterogeneous diagnostic criteria for sarcopenia, estimates of its prevalence present a wide variation, leading to new criteria having been recently proposed for its diagnosis, emphasizing muscle strength and function rather than skeletal muscle mass. The primary objective of this study is to evaluate the prevalence of sarcopenia and/or dynapenia in individuals with HF with reduced LVEF according to the most recent criteria, and compare the gene and protein expression of those patients with and without sarcopenia. The secondary objectives are to evaluate the association of sarcopenia and/or dynapenia with the risk of clinical events and death, quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength. The participants will answer questionnaires to evaluate sarcopenia and quality of life, and will undergo the following tests: handgrip strength, gait speed, dual-energy X-ray absorptiometry, respiratory muscle strength, cardiopulmonary exercise, as well as genomic and proteomic analysis, and dosage of N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15. An association between sarcopenia and/or dynapenia with unfavorable clinical evolution is expected to be found, in addition to reduced quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength.

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The muscle hypothesis revisited

Cited by 6 publications

References 16 publications

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems

Exercise Training Enhances Angiogenesis-Related Gene Responses in Skeletal Muscle of Patients with Chronic Heart Failure

Prevalence and impact of sarcopenia in individuals with heart failure with reduced ejection fraction (the SARC-HF study): A prospective observational study protocol

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