Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid‐grade septic group than in the low‐grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid‐grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.

Dexmedetomidine is a commonly used α2-adreno-ceptor agonist, which affects various organs, including providing beneficial effects on the heart. However, the mechanism underlying the cardiac benefit remains to be fully elucidated. In the present study, it was demonstrated that dexmedetomidine pretreatment on primary cultured rat cardiomyocytes protected against reactive oxygen species (ROS)‑induced apoptosis. In terms of the potential mechanism, it was demonstrated that dexmedetomidine inhibited mitochondrial biogenesis and mitochondrial respiratory complexes, but with increased coupling efficiency. However, dexmedetomidine upregulated mitochondrial membrane potential (Δψm) and resisted against the loss of Δψm induced by carbonilcyanide p‑triflouromethoxyphenylhydrazone. Due to the importance of mitochondria affecting ROS, the present study investigated the dexmedetomidine‑suppressed mitochondrial response to H2O2 stimulation, which was explained by suppressed ROS levels and the suppression of the increased oxygen consumption rate. Results demonstrated for the first time, to the best of our knowledge, a novel protective mechanism for dexmedetomidine on cardiomyocytes through the attenuated response of mitochondria towards H2O2, which had a protective effect against ROS‑induced apoptosis.

Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1β (NRG-1β) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1β therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1β application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1β treatment. In vitro, the effects of NRG-1β on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1β inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1β. And NRG-1β activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1β, while MK-2206 blocked these effects of NRG-1β. In conclusion, our findings underlined that NRG-1β could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.

The intraoperative lung protective effect of mechanical ventilation of different positive end-expiratory pressure (PEEP) levels on patients undergoing abdominal laparoscopic surgery with the steep Trendelenburg position remains undefined. The purpose of the study was to explore the optimal PEEP. Sixty patients scheduled for abdominal laparoscopic surgery were randomized to four groups including: PEEP 0, 4, 8 and 12 cmH2O. The pulmonary dynamic compliance (Cdyn), dead space to tidal volume ratio (VD/VT), and intrapulmonary shunt ratio (QS/QT) were measured after anesthesia induction (T0), 5 min after pneumoperitoneum (PNP) with position change (T1), 30 (T2) and 60 min (T3) after PEEP, and end of surgery (T4). Cdyn increased when different levels of PEEP (including the 4, 8, and 12 cmH2O) were used vs. no PEEP (P<0.05). The VD/VT in PEEP 8 and 12 cmH2O were significantly improved than no PEEP (P<0.05). Meanwhile, the QS/QT in PEEP 12 cmH2O was higher than others during the procedures. A moderate PEEP level (8 cmH2O) with low tidal volume was sufficient to improve Cdyn and to decrease VD/VT without increasing QS/QT, which was suggested to be a good choice of intraoperative lung protective ventilation during abdominal laparoscopic surgery with Trendelenburg position.