Abstract
Diaphragm dysfunction is prevalent in the progress of respiratory dysfunction in various critical illnesses. Respiratory muscle weakness may result in insufficient ventilation, coughing reflection suppression, pulmonary infection, and difficulty in weaning off respirators. All of these further induce respiratory dysfunction and even threaten the patients' survival. The potential mechanisms of diaphragm atrophy and dysfunction include impairment of myofiber protein anabolism, enhancement of myofiber protein degradation, release of inflammatory mediators, imbalance of metabolic hormones, myonuclear apoptosis, autophagy, and oxidative stress. Among these contributors, mitochondrial oxidative stress is strongly implicated to play a key role in the process as it modulates diaphragm protein synthesis and degradation, induces protein oxidation and functional alteration, enhances apoptosis and autophagy, reduces mitochondrial energy supply, and is regulated by inflammatory cytokines via related signaling molecules. This review aims to provide a concise overview of pathological mechanisms of diaphragmatic dysfunction in critically ill patients, with special emphasis on the role and modulating mechanisms of mitochondrial oxidative stress.
Highlights
Respiratory dysfunction is one of the predominant complications of various critical care patients. e common causes for respiratory dysfunction include acute respiratory distress syndrome (ARDS), inhalation injury, blast injury, sepsis, pneumonia, and ventilator-induced lung injury [1, 2], which impair air exchange and ventilation by inducing bleeding, inflammation, infection, edema, exudates increase, mucosal injury, airway obstruction, and atelectasis
Similar results were observed in sepsis, chronic obstructive pulmonary disease, cachexia, diabetes, use of corticosteroid, and other critical conditions [18,19,20,21,22,23,24]. All of these results suggest that diaphragm dysfunction is common in critically ill patients and is critical for prognosis of various critical illnesses
It was reported that dexamethasone injection significantly increased skeletal muscle protein catabolism and chronic low-dose triamcinolone treatment caused a decrease in diaphragm muscle energy status together with a mismatch between glycolysis and oxidative metabolism, which further induced diaphragm wasting and insufficiency of energy supply in rats [25, 26]
Summary
Respiratory dysfunction is one of the predominant complications of various critical care patients. e common causes for respiratory dysfunction include acute respiratory distress syndrome (ARDS), inhalation injury, blast injury, sepsis, pneumonia, and ventilator-induced lung injury [1, 2], which impair air exchange and ventilation by inducing bleeding, inflammation, infection, edema, exudates increase, mucosal injury, airway obstruction, and atelectasis. It was reported that dexamethasone injection significantly increased skeletal muscle protein catabolism and chronic low-dose triamcinolone treatment caused a decrease in diaphragm muscle energy status together with a mismatch between glycolysis and oxidative metabolism, which further induced diaphragm wasting and insufficiency of energy supply in rats [25, 26]. Low-dose recombinant human growth hormone treatment significantly improved height, weight, lean body mass and muscle mass, cardiac function, and muscle strength in pediatric burn patients [27] Elevated inflammatory mediators, such as tumor necrosis factor–α (TNF-α) and soluble Fas ligand in serum of severely scald rats, were significantly decreased by insulin treatment as indicated by our previous study [28]. Nuclear factor-κB (NFκB) in the cytoplasm is activated through signals such as intracellular phosphoinositide and translocated into the nucleus, which trigger the processes of gene transcription
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