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diaphragm disuse

Gerald S Supinski, Peter E Morris, Sanjay Dhar, Leigh Ann Callahan
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...
April 2018: Chest
Takeshi Yoshida, Yuji Fujino, Marcelo B P Amato, Brian P Kavanagh
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...
April 15, 2017: American Journal of Respiratory and Critical Care Medicine
David Berger, Stefan Bloechlinger, Stephan von Haehling, Wolfram Doehner, Jukka Takala, Werner J Z'Graggen, Joerg C Schefold
Muscular weakness and muscle wasting may often be observed in critically ill patients on intensive care units (ICUs) and may present as failure to wean from mechanical ventilation. Importantly, mounting data demonstrate that mechanical ventilation itself may induce progressive dysfunction of the main respiratory muscle, i.e. the diaphragm. The respective condition was termed 'ventilator-induced diaphragmatic dysfunction' (VIDD) and should be distinguished from peripheral muscular weakness as observed in 'ICU-acquired weakness (ICU-AW)'...
September 2016: Journal of Cachexia, Sarcopenia and Muscle
Hassib Narchi, Fares Chedid
Continuous improvements in perinatal care have resulted in increased survival of premature infants. Their immature lungs are prone to injury with mechanical ventilation and this may develop into chronic lung disease (CLD) or bronchopulmonary dysplasia. Strategies to minimize the risk of lung injury have been developed and include improved antenatal management (education, regionalization, steroids, and antibiotics), exogenous surfactant administration and reduction of barotrauma by using exclusive or early noninvasive ventilatory support...
June 26, 2015: World Journal of Methodology
Leo M A Heunks, Jonne Doorduin, Johannes G van der Hoeven
PURPOSE OF REVIEW: The present review summarizes developments in the field of respiratory muscle monitoring, in particular in critically ill patients. RECENT FINDINGS: Patients admitted to the ICU may develop severe respiratory muscle dysfunction in a very short time span. Among other factors, disuse and sepsis have been associated with respiratory muscle dysfunction in these patients. Because weakness is associated with adverse outcome, including prolonged mechanical ventilation and mortality, it is surprising that respiratory muscle dysfunction largely develops without being noticed by the clinician...
February 2015: Current Opinion in Critical Care
Christian S Bruells, Karen Maes, Rolf Rossaint, Debby Thomas, Nele Cielen, Christian Bleilevens, Ingmar Bergs, Ursina Loetscher, Agnes Dreier, Ghislaine Gayan-Ramirez, Brad J Behnke, Joachim Weis
OBJECTIVE: Mechanical ventilation (MV) is a life saving intervention for patients with respiratory failure. Even after 6 hours of MV, diaphragm atrophy and dysfunction (collectively referred to as ventilator-induced diaphragmatic dysfunction, VIDD) occurs in concert with a blunted blood flow and oxygen delivery. The regulation of hypoxia sensitive factors (i.e. hypoxia inducible factor 1α, 2α (HIF-1α,-2α), vascular endothelial growth factor (VEGF)) and angio-neogenetic factors (angiopoietin 1-3, Ang) might contribute to reactive and compensatory alterations in diaphragm muscle...
2013: PloS One
Pedro A Mendez-Tellez, Dale M Needham
Critically ill patients requiring mechanical ventilation are frequently subjected to long periods of physical inactivity, leading to skeletal muscle atrophy and muscle weakness. Disuse muscle atrophy is the result of complex mechanisms, including altered protein turnover and disturbed redox signaling. These ICU-acquired complications are associated with longer duration of mechanical ventilation, prolonged ICU and hospital stays, and poorer functional status at hospital discharge. Similarly, there is growing evidence that continuous mandatory ventilation alters diaphragmatic structure and contractile function and promotes oxidative injury, resulting in a rapid-onset diaphragmatic atrophy and weakness, which most likely delays discontinuing mechanical ventilation...
October 2012: Respiratory Care
Huibin Tang, Myung Lee, Orr Sharpe, Louis Salamone, Emily J Noonan, Chuong D Hoang, Sanford Levine, William H Robinson, Joseph B Shrager
Glycolysis is the initial step of glucose catabolism and is up-regulated in cancer cells (the Warburg Effect). Such shifts toward a glycolytic phenotype have not been explored widely in other biological systems, and the molecular mechanisms underlying the shifts remain unknown. With proteomics, we observed increased glycolysis in disused human diaphragm muscle. In disused muscle, lung cancer, and H(2)O(2)-treated myotubes, we show up-regulation of the rate-limiting glycolytic enzyme muscle-type phosphofructokinase (PFKm, >2 fold, P<0...
November 2012: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
B Bissett, I A Leditschke, J D Paratz, R J Boots
Respiratory muscle dysfunction is associated with prolonged and difficult weaning from mechanical ventilation. This dysfunction in ventilator-dependent patients is multifactorial: there is evidence that inspiratory muscle weakness is partially explained by disuse atrophy secondary to ventilation, and positive end-expiratory pressure can further reduce muscle strength by negatively shifting the length-tension curve of the diaphragm. Polyneuropathy is also likely to contribute to apparent muscle weakness in critically ill patients, and nutritional and pharmaceutical effects may further compound muscle weakness...
March 2012: Anaesthesia and Intensive Care
Richard H Kallet
Since the early 1970s there has been an ongoing debate regarding the wisdom of promoting unassisted spontaneous breathing throughout the course of critical illness in patients with severe respiratory failure. The basis of this debate has focused on the clinical relevance of opposite problems. Historically, the term "disuse atrophy" has described a situation wherein sustained inactivity of the respiratory muscles (ie, passive ventilation) results in deconditioning and weakness. More recently it has been referred to as "ventilator-induced diaphragmatic dysfunction...
February 2011: Respiratory Care
Sanford Levine, Chhanda Biswas, Jamil Dierov, Robert Barsotti, Joseph B Shrager, Taitan Nguyen, Seema Sonnad, John C Kucharchzuk, Larry R Kaiser, Sunil Singhal, Murat T Budak
RATIONALE: Patients on mechanical ventilation who exhibit diaphragm inactivity for a prolonged time (case subjects) develop decreases in diaphragm force-generating capacity accompanied by diaphragm myofiber atrophy. OBJECTIVES: Our objectives were to test the hypotheses that increased proteolysis by the ubiquitin-proteasome pathway, decreases in myosin heavy chain (MyHC) levels, and atrophic AKT-FOXO signaling play major roles in eliciting these pathological changes associated with diaphragm disuse...
February 15, 2011: American Journal of Respiratory and Critical Care Medicine
Sabah N A Hussain, Mahroo Mofarrahi, Ioanna Sigala, Ho Cheol Kim, Theodoros Vassilakopoulos, Francois Maltais, Ion Bellenis, Rakesh Chaturvedi, Stewart B Gottfried, Peter Metrakos, Gawiyou Danialou, Stefan Matecki, Samir Jaber, Basil J Petrof, Peter Goldberg
RATIONALE: Controlled mechanical ventilation (CMV) results in atrophy of the human diaphragm. The autophagy-lysosome pathway (ALP) contributes to skeletal muscle proteolysis, but its contribution to diaphragmatic protein degradation in mechanically ventilated patients is unknown. OBJECTIVES: To evaluate the autophagy pathway responses to CMV in the diaphragm and limb muscles of humans and to identify the roles of FOXO transcription factors in these responses. METHODS: Muscle biopsies were obtained from nine control subjects and nine brain-dead organ donors...
December 1, 2010: American Journal of Respiratory and Critical Care Medicine
Ashley J Smuder, Andreas N Kavazis, Matthew B Hudson, W Bradley Nelson, Scott K Powers
Oxidative stress has been linked to accelerated rates of proteolysis and muscle fiber atrophy during periods of prolonged skeletal muscle inactivity. However, the mechanism(s) that links oxidative stress to muscle protein degradation remains unclear. A potential connection between oxidants and accelerated proteolysis in muscle fibers is that oxidative modification of myofibrillar proteins may enhance their susceptibility to proteolytic processing. In this regard, it is established that protein oxidation promotes protein recognition and degradation by the 20S proteasome...
October 15, 2010: Free Radical Biology & Medicine
Richard D Griffiths, Jesse B Hall
OBJECTIVE: Severe weakness is being recognized as a complication that impacts significantly on the pace and degree of recovery and return to former functional status of patients who survive the organ failures that mandate life-support therapies such as mechanical ventilation. Despite the apparent importance of this problem, much remains to be understood about its incidence, causes, prevention, and treatment. DESIGN: Review from literature and an expert round-table...
March 2010: Critical Care Medicine
Valerie P Wright, Peter J Reiser, Thomas L Clanton
Skeletal muscles produce transient reactive oxygen species (ROS) in response to intense stimulation, disuse atrophy, heat stress, hypoxia, osmotic stress, stretch and cell receptor activation. The physiological significance is not well understood. Protein phosphatases (PPases) are known to be highly sensitive to oxidants and could contribute to many different signalling responses in muscle. We tested whether broad categories of PPases are inhibited by levels of acute oxidant exposure that do not result in loss of contractile function or gross oxidative stress...
December 1, 2009: Journal of Physiology
Catherine Sh Sassoon, Vincent J Caiozzo
Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress...
2009: Critical Care: the Official Journal of the Critical Care Forum
Bert Blaauw, Marta Canato, Lisa Agatea, Luana Toniolo, Cristina Mammucari, Eva Masiero, Reimar Abraham, Marco Sandri, Stefano Schiaffino, Carlo Reggiani
A better understanding of the signaling pathways that control muscle growth is required to identify appropriate countermeasures to prevent or reverse the loss of muscle mass and force induced by aging, disuse, or neuromuscular diseases. However, two major issues in this field have not yet been fully addressed. The first concerns the pathways involved in leading to physiological changes in muscle size. Muscle hypertrophy based on perturbations of specific signaling pathways is either characterized by impaired force generation, e...
November 2009: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sanford Levine, Taitan Nguyen, Nyali Taylor, Michael E Friscia, Murat T Budak, Pamela Rothenberg, Jianliang Zhu, Rajeev Sachdeva, Seema Sonnad, Larry R Kaiser, Neal A Rubinstein, Scott K Powers, Joseph B Shrager
BACKGROUND: The combination of complete diaphragm inactivity and mechanical ventilation (for more than 18 hours) elicits disuse atrophy of myofibers in animals. We hypothesized that the same may also occur in the human diaphragm. METHODS: We obtained biopsy specimens from the costal diaphragms of 14 brain-dead organ donors before organ harvest (case subjects) and compared them with intraoperative biopsy specimens from the diaphragms of 8 patients who were undergoing surgery for either benign lesions or localized lung cancer (control subjects)...
March 27, 2008: New England Journal of Medicine
Krzysztof E Kowalski, Jaroslaw R Romaniuk, Anthony F DiMarco
Following spinal cord injury, muscles below the level of injury develop variable degrees of disuse atrophy. The present study assessed the physiological changes of the expiratory muscles in a cat model of spinal cord injury. Muscle fiber typing, cross-sectional area, muscle weight, and changes in pressure-generating capacity were assessed in five cats spinalized at the T(6) level. Airway pressure (P)-generating capacity was monitored during lower thoracic spinal cord stimulation before and 6 mo after spinalization...
April 2007: Journal of Applied Physiology
Seiro Oya, T Miyoshi, F Kato, K Maki, H Hayashi, T Yamada, S Yamamoto, M Hiratsuka, T Shiraishi, A Iwasaki, T Shirakusa
The case was a 59-year-old man who has a history of left mediastinal tumor resection with left phrenicectomy. The elevated diaphragm revealed by chest X-ray 7 years after the operation led to diagnosis of diaphragmatic eventration. Since any symptom was seen in the early period, "wait and watch" strategy was done for management. Both the abdominal enlarged feeling and the dyspnea on effort were appeared 10 years after the operation. Under the speculation of these symptoms related to the elevated abdominal organs came up with diaphragmatic eventration, surgical method the plication of the diaphragm was performed...
May 2005: Kyobu Geka. the Japanese Journal of Thoracic Surgery
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