RESUMO
Systemic inflammatory response syndrome (SIRS) is a sepsis-associated inflammatory state and a self-defense mechanism against specific and nonspecific stimuli. Ketamine influences many key processes that are altered during sepsis. However, the underlying mechanisms remain incompletely understood. In this study, TNF-α-treated mice, as well as HT-29 and L929 cell models, were applied to characterize TNF-α-induced systemic and local cecal tissue inflammatory responses. Behavioral, biochemical, histological, and molecular biological approaches were applied to illustrate the related processes. Mice with TNF-α-induced SIRS showed systemic and local cecal tissue inflammatory responses, as indicated by increased levels of high mobility group box 1 protein (HMGB1), chemokines (C-X-C motif) ligand 10 (CXCL10), interleukin-6 (IL-6), and IL-10, as well as high mortality. Ketamine pretreatment alleviated death rates, symptoms, and the production of inflammatory cytokines induced by TNF-α in mice. Moreover, ketamine also protected the mice from TNF-α-induced cecal damage by suppressing the phosphorylation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). In addition, our results showed that ketamine efficiently inhibited TNF-α-induced necroptosis in HT-29 and L929 cells. Furthermore, we explored the mechanism using different L929 cell lines. The results displayed that ketamine inhibited TNF-α-induced necroptosis by enhancing RIP1 ubiquitination and reducing the RIP1-RIP3 and RIP3-MLKL interactions, as well as the formation of necrosomes. Thus, our study may provide a new theoretical and experimental basis for treating diseases characterized by SIRS-associated inflammatory factor storms. Moreover, our exploration may provide potential molecular mechanisms and targets for therapeutic intervention and clinical application of ketamine.
RESUMO
In asleep-awake-asleep anaesthesia, removal and reinsertion of endotracheal tubes are associated with significant difficulty and risk. To overcome this, an oesophageal naso-pharyngeal catheter was developed. Its sealed distal end is placed in the oesophagus via the nose and the proximal end is connected to a ventilator or breathing circuit. For anaesthesia, the distal end balloon is inflated to seal the oesophagus and the larger proximal balloon is inflated to seal the naso- and oro-pharyngeal cavities. Ventilation occurs via the side holes on the tube located between the balloons and which sit over the laryngeal inlet. This eliminates the need to remove and reestablish airway devices with the associated risks. The authors report the preliminary experience using this device in 17 patients who underwent awake craniotomy for surgery adjacent to the 'eloquent' areas.