diaphragm disuse

Prolonged controlled mechanical ventilation (CMV) can cause diaphragm fiber atrophy and inspiratory muscle weakness, resulting in diaphragmatic contractile dysfunction, called ventilator-induced diaphragm dysfunction (VIDD). VIDD is associated with higher rates of in-hospital deaths, nosocomial pneumonia, difficulty weaning from ventilators, and increased costs. Currently, appropriate clinical strategies to prevent and treat VIDD are unavailable, necessitating the importance of exploring the mechanisms of VIDD and suitable treatment options to reduce the healthcare burden...

The diaphragm is the main component of the respiratory muscle pump. Diaphragm dysfunction can cause dyspnea and exercise intolerance, and predisposes affected individuals to respiratory failure. In mechanically ventilated patients, the diaphragm is susceptible to atrophy and dysfunction through disuse and other mechanisms. This contributes to failure to wean and poor long-term clinical outcomes. Point-of-care ultrasound provides a valid and reproducible method for evaluating diaphragm thickness and contractile activity (thickening fraction during inspiration) that can be readily employed by clinicians and researchers alike...

No abstract text is available yet for this article.

Diaphragm dysfunction is a highly prevalent phenomenon in patients receiving mechanical ventilation, mainly due to ventilatory over-assistance and the development of diaphragm disuse atrophy. Promoting diaphragm activation whenever possible and facilitating an adequate interaction between the patient and the ventilator is encouraged at the bedside to avoid myotrauma and further lung injury. Eccentric contractions of the diaphragm are defined as muscle activation while muscle fibers are lengthening within the exhalation phase...

The vegetal polyphenol curcumin displays beneficial effects against skeletal muscle derangement induced by oxidative stress, disuse or aging. Since oxidative stress and inflammation are involved in the progression of muscle dystrophy, the effects of curcumin administration were investigated in the diaphragm of mdx mice injected intraperitoneally or subcutaneously with curcumin for 4-12-24 weeks. Curcumin treatment independently of the way and duration of administration (i) ameliorated myofiber maturation index without affecting myofiber necrosis, inflammation and degree of fibrosis; (ii) counteracted the decrease in type 2X and 2B fiber percentage; (iii) increased about 30% both twitch and tetanic tensions of diaphragm strips; (iv) reduced myosin nitrotyrosination and tropomyosin oxidation; (v) acted on two opposite nNOS regulators by decreasing active AMP-Kinase and increasing SERCA1 protein levels, the latter effect being detectable also in myotube cultures from mdx satellite cells...

In clinical conditions such as diaphragm paralysis or mechanical ventilation, disuse-induced diaphragmatic dysfunction (DIDD) is a condition that poses a threat to life. MuRF1 is a key E3-ligase involved in regulating skeletal muscle mass, function, and metabolism, which contributes to the onset of DIDD. We investigated if the small-molecule mediated inhibition of MuRF1 activity (MyoMed-205) protects against early DIDD after 12 h of unilateral diaphragm denervation. Wistar rats were used in this study to determine the compound's acute toxicity and optimal dosage...

Mechanical ventilation injures not only the lungs but also the diaphragm, resulting in dysfunction associated with poor outcomes. The chief mechanisms of ventilator-induced diaphragm dysfunction are : disuse atrophy due to insufficient contraction and excessive ventilatory support ; concentric load-induced injury due to excessive contraction and insufficient ventilatory support ; eccentric load-induced injury due to contraction during the expiratory phase ; and longitudinal atrophy caused by high positive end-expiratory pressure...

The Na,K-ATPase plays an important role in adaptation to hypoxia. Prolonged hypoxia results in loss of skeletal muscle mass, structure, and performance. However, hypoxic preconditioning is known to protect against a variety of functional impairments. In this study, we tested the possibility of mild hypoxia to modulate the Na,K-ATPase and to improve skeletal muscle electrogenesis. The rats were subjected to simulated high-altitude (3000 m above sea level) hypobaric hypoxia (HH) for 3 h using a hypobaric chamber...

Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise preconditioning. Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy. The mechanism(s) responsible for exercise preconditioning remain unknown and are explored in these experiments. Specifically, we investigated the impact of endurance exercise training on key components of the renin-angiotensin system (RAS). The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensin II type I receptors (AT1Rs) promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors (MasRs) inhibits the atrophic signaling of the classical RAS pathway...

Skeletal muscle fibers are malleable and undergo rapid remodeling in response to increased contractile activity (i.e., exercise) or prolonged periods of muscle inactivity (e.g., prolonged bedrest). Exploration of the cell signaling pathways regulating these skeletal muscle adaptations reveal that redox signaling pathways play a key role in the control of muscle remodeling during both exercise and prolonged muscle inactivity. In this regard, muscular exercise results in an acute increase in the production of reactive oxygen species (ROS) in the contracting fibers; however, this contraction-induced rise in ROS production rapidly declines when contractions cease...

Maintaining spontaneous breathing has both potentially beneficial and deleterious consequences in patients with acute respiratory failure, depending on the balance that can be obtained between the protecting and damaging effects on the lungs and the diaphragm. Neurally adjusted ventilatory assist (NAVA) is an assist mode, which supplies the respiratory system with a pressure proportional to the integral of the electrical activity of the diaphragm. This proportional mode of ventilation has the theoretical potential to deliver lung- and respiratory-muscle-protective ventilation by preserving the physiologic defense mechanisms against both lung overdistention and ventilator overassistance, as well as reducing the incidence of diaphragm disuse atrophy while maintaining patient-ventilator synchrony...

The patient was a 67-year-old male diagnosed with adenocarcinoma of the esophagogastric junction. The esophagus was markedly dilated due to severe stenosis, and aspiration pneumonia was observed. Therefore, he was treated with a W- ED tube for simultaneous esophageal decompression and enteral nutrition. Two weeks of W-ED tube placement improved esophageal dilatation and pneumonia while maintaining nutritional status; thus, he underwent proximal gastrectomy, lower esophagectomy and combined resection of distal pancreas, spleen and left crus of diaphragm with jejunal interposition reconstruction...

[Figure: see text].

Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfortunately, an unintended consequence of prolonged MV is the rapid development of diaphragmatic atrophy and contractile dysfunction, known as ventilator-induced diaphragm dysfunction (VIDD). Although the mechanism(s) responsible for VIDD are not fully understood, abundant evidence reveals that oxidative stress leading to the activation of the major proteolytic systems (i.e., autophagy, ubiquitin-proteasome, caspase, and calpain) plays a dominant role...

While the role of circulating ouabain-like compounds in the cardiovascular and central nervous systems, kidney and other tissues in health and disease is well documented, little is known about its effects in skeletal muscle. In this study, rats were intraperitoneally injected with ouabain (0.1-10 µg/kg for 4 days) alone or with subsequent injections of lipopolysaccharide (1 mg/kg). Some rats were also subjected to disuse for 6 h by hindlimb suspension. In the diaphragm muscle, chronic ouabain (1 µg/kg) hyperpolarized resting potential of extrajunctional membrane due to specific increase in electrogenic transport activity of the 2 Na,K-ATPase isozyme and without changes in 1 and 2 Na,K-ATPase protein content...

Exercise capacity is a strong predictor of all-cause mortality. Skeletal muscle mitochondrial respiratory capacity, its biggest contributor, adapts robustly to changes in energy demands induced by contractile activity. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are regulated. Here, we show that exercise training or muscle disuse alters mitochondrial membrane phospholipids including phosphatidylethanolamine (PE)...

Intensive care unit-acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient's ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW)...

BACKGROUND: Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure...

The diaphragm is the major muscle of inspiration, and its function is critical for optimal respiration. Diaphragmatic failure has long been recognized as a major contributor to death in a variety of systemic neuromuscular disorders. More recently, it is increasingly apparent that diaphragm dysfunction is present in a high percentage of critically ill patients and is associated with increased morbidity and mortality. In these patients, diaphragm weakness is thought to develop from disuse secondary to ventilator-induced diaphragm inactivity and as a consequence of the effects of systemic inflammation, including sepsis...

Spontaneous respiratory effort during mechanical ventilation has long been recognized to improve oxygenation, and because oxygenation is a key management target, such effort may seem beneficial. Also, disuse and loss of peripheral muscle and diaphragm function is increasingly recognized, and thus spontaneous breathing may confer additional advantage. Reflecting this, epidemiologic data suggest that the use of partial (vs. full) support modes of ventilation is increasing. Notwithstanding the central place of spontaneous breathing in mechanical ventilation, accumulating evidence indicates that it may cause-or worsen-acute lung injury, especially if acute respiratory distress syndrome is severe and spontaneous effort is vigorous...