Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease

Giannoni, Alberto; Aimo, Alberto; Mancuso, Michelangelo; Piepoli, Massimo F; Orsucci, Daniele; Aquaro, Giovanni Donato; Barison, Andrea; Marchi, Daniele De; Taddei, C; Cameli, Matteo; Raglianti, Valentina; Siciliano, Gabriele; Passino, Claudio; Emdin, Michele

doi:10.1002/ejhf.782

Cited by 19 publications

(23 citation statements)

References 38 publications

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“…They studied 25 patients with mitochondrial disease and no known cardiac involvement. Compared with normal subjects, these patients had reduced exercise capacity, as shown by both a lower peak oxygen consumption and an increased VE/VCO 2 slope, and these values correlated with increased ergoreflex sensitivity, consistent with the role of skeletal muscle abnormalities as major determinants of exercise intolerance …”

Section: Determinants Of Exercise Capacitysupporting

confidence: 62%

See 1 more Smart Citation

December 2017 at a glance: left ventricular ejection fraction, exercise capacity, peripartum cardiomyopathy

Metra

2017

European J of Heart Fail

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Section: Determinants Of Exercise Capacitysupporting

confidence: 62%

“…The role of reflex mechanisms arising from the skeletal muscles is also shown by Giannoni et al . They studied 25 patients with mitochondrial disease and no known cardiac involvement.…”

Section: Determinants Of Exercise Capacitymentioning

confidence: 71%

December 2017 at a glance: left ventricular ejection fraction, exercise capacity, peripartum cardiomyopathy

Metra

2017

European J of Heart Fail

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“…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. 33,34 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. To interrupt this vicious cycle, maintaining or increasing the muscle mass may have potential as a new strategy to treat aspiration pneumonia.…”

Section: Discussionmentioning

confidence: 67%

“…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: Discussionmentioning

confidence: 99%

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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“…A paper by Giannoni et al . in this issue of the Journal significantly extends these findings by addressing a highly symptomatic and adverse syndrome, that of mitochondrial myopathy . What is so important is that these are primary genetic conditions that affect skeletal muscle rather than being secondary changes induced by complex chronic disorders, such as CHF.…”

mentioning

confidence: 84%

The muscle hypothesis revisited

Coats

2017

European J of Heart Fail

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Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease

Abstract: Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation.

Cited by 19 publications

References 38 publications

December 2017 at a glance: left ventricular ejection fraction, exercise capacity, peripartum cardiomyopathy

December 2017 at a glance: left ventricular ejection fraction, exercise capacity, peripartum cardiomyopathy

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

The muscle hypothesis revisited

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