Sepsis-Associated Muscle Wasting: A Comprehensive Review from Bench to Bedside.

Sepsis-associated muscle wasting (SAMW) is characterized by decreased muscle mass, reduced muscle fiber size, and decreased muscle strength, resulting in persistent physical disability accompanied by sepsis. Systemic inflammatory cytokines are the main cause of SAMW, which occurs in 40-70% of patients with sepsis. The pathways associated with the ubiquitin-proteasome and autophagy systems are particularly activated in the muscle tissues during sepsis and may lead to muscle wasting. Additionally, expression of muscle atrophy-related genes Atrogin-1 and MuRF-1 are seemingly increased via the ubiquitin-proteasome pathway. In clinical settings, electrical muscular stimulation, physiotherapy, early mobilization, and nutritional support are used for patients with sepsis to prevent or treat SAMW. However, there are no pharmacological treatments for SAMW, and the underlying mechanisms are still unknown. Therefore, research is urgently required in this field.

Unloading-induced atrophy and decreased oxidative capacity of the soleus muscle in rats are reversed by pre- and postconditioning with mild hyperbaric oxygen.

Our aim was to determine the effects of pre- and/or postconditioning with mild hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the properties of the soleus muscle that was atrophied by hindlimb suspension-induced unloading. Twelve groups of 8-week-old rats were housed under normobaric conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2 weeks with their hindlimbs either unloaded via suspension or not unloaded. Six groups subsequently were either housed under normobaric conditions or exposed to mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover under reloaded conditions (unrestricted normal cage activity). Muscle weights, cross-sectional areas of all fiber types, oxidative capacity (muscle succinate dehydrogenase activity and fiber succinate dehydrogenase staining intensity) decreased, and a shift of fibers from type I to type IIA and type IIC was observed after hindlimb unloading. In addition, mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α decreased, whereas those of forkhead box-containing protein O1 increased after hindlimb unloading. Muscle atrophy and decreased oxidative capacity were unaffected by either pre- or postconditioning with mild hyperbaric oxygen. In contrast, these changes were followed by a return to nearly normal levels after 2 weeks of reloading when pre- and postconditioning were combined. Therefore, a combination of pre- and postconditioning with mild hyperbaric oxygen can be effective against the atrophy and decreased oxidative capacity of skeletal muscles associated with hindlimb unloading.