简介：AbstractImportance:Dexmedetomidine inhibits the inflammatory response associated with cardiopulmonary bypass (CPB) and protects neural function. However, the mechanism of dexmedetomidine’s anti-inflammatory pathway is unclear.Objective:To investigate the effect of dexmedetomidine on the cognitive level and expression of inflammatory factors in children with congenital heart disease undergoing intraoperative CPB.Methods:Ninety children with congenital heart disease were recruited and randomly divided into 3 groups of 30 children in each. In Group 1, a 1.0 µg·kg-1·h-1 intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia, followed by a 0.2 µg·kg-1·h-1 infusion until the surgical incision. In Group 2, a 0.5 µg/kg intravenous bolus of dexmedetomidine was administered 10 minutes after induction of anesthesia, followed by a 0.1 µg·kg-1·h-1 infusion until the surgical incision. The control group was given physiological saline using the same method as in Groups 1 and 2. The serum levels of nuclear factor-kappa B (NF-κB), S-100β protein, neuron-specific enolase (NSE), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured before the surgery (T1), at the end of CPB (T2), 2 hours after CPB (T3), 6 hours after CPB (T4), and 24 hours after CPB (T5). The Wechsler Intelligence Scale for children (WISC) was measured before the operation and at 3, 6, and 12 months after the operation to evaluate the neurodevelopmental state of the children.Results:The levels of the NF-κB, S-100β protein, NSE, TNF-α, IL-6 were significantly higher at T2, T3, or T4 than before the surgery (T1) in the control group or the dexmedetomidine groups. However, the increases of NF-κB, TNF-α, IL-6, S-100β and NSE levels were significantly smaller in the dexmedetomidine groups than those in the control group (P < 0.017). The WISC scores were similar among the three groups before or after the operation.Interpretation:The increases in NF-κB, TNF-α, and IL-6 levels indicated aggravation of the inflammatory reaction and the increase S-100β protein and NSE levels indicated that the nervous system was damaged. Administration of dexmedetomidine to children with congenital heart disease undergoing intraoperative CPB can inhibit the inflammatory response and may ameliorate the neurodevelopmental damage caused by CPB.

简介：AbstractBackground:Excessive inflammatory responses play a critical role in the development of severe acute pancreatitis (SAP), and controlling such inflammation is vital for managing this often fatal disease. Dexmedetomidine has been reported to possess protective properties in inflammatory diseases. Therefore, this study aimed to investigate whether dexmedetomidine pre-treatment exerts an anti-inflammatory effect in rats with SAP induced by sodium taurocholate, and if so, to determine the potential mechanism.Methods:SAP was induced with sodium taurocholate. Rats received an intraperitoneal injection of dexmedetomidine 30 min before sodium taurocholate administration. α-bungarotoxin, a selective alpha-7 nicotinic acetylcholine receptor (α7nAchR) antagonist, was injected intra-peritoneally 30 min before dexmedetomidine administration. The role of the vagus nerve was evaluated by performing unilateral cervical vagotomy before the administration of dexmedetomidine. Efferent discharge of the vagal nerve was recorded by the BL-420F Data Acquisition & Analysis System. Six hours after onset, serum pro-inflammatory cytokine (tumor necrosis factor α [TNF-α] and interleukin 6 [IL-6]) levels and amylase levels were determined using an enzyme-linked immunosorbent assay and an automated biochemical analyzer, respectively. Histopathological changes in the pancreas were observed after hematoxylin and eosin staining and scored according to Schmidt criteria.Results:Pre-treatment with dexmedetomidine significantly decreased serum levels of TNF-α, IL-6, and amylase, strongly alleviating pathological pancreatic injury in the rat model of SAP (TNF-α: 174.2 ± 30.2 vs. 256.1±42.4 pg/ml; IL-6: 293.3 ± 46.8 vs. 421.7 ± 48.3 pg/ml; amylase: 2102.3 ± 165.3 vs. 3186.4 ± 245.2 U/L). However, the anti-inflammatory and pancreatic protective effects were abolished after vagotomy or pre-administration of α-bungarotoxin. Dexmedetomidine also significantly increased the discharge frequency and amplitude of the cervical vagus nerve in the SAP rat model (discharge frequency: 456.8 ± 50.3 vs. 332.4 ± 25.1 Hz; discharge amplitude: 33.4 ± 5.3 vs. 20.5 ± 2.9 μV).Conclusions:Dexmedetomidine administration attenuated the systemic inflammatory response and local pancreatic injury caused by SAP in rats through the cholinergic anti-inflammatory pathway involving vagus-and α7nAChR-dependent mechanisms.