Background Cardiac surgery is associated with a high risk of cardiovascular and other complications that translate into increased mortality and healthcare costs. This retrospective study was designed to determine whether the perioperative use of dexmedetomidine could reduce the incidence of complications and mortality following cardiac surgery. Methods and Results 1,134 patients who underwent CABG and CABG plus valvular and/or other procedures were included. 568 received intravenous dexmedetomidine infusion and 566 did not. Data were adjusted with propensity scores and multivariate logistic regression was used. The primary outcomes measured included mortality and postoperative major adverse cardiocerebral events (MACE: stroke, coma, perioperative myocardial infarction, heart block or cardiac arrest). Secondary outcomes included renal failure, sepsis, delirium, postoperative ventilation hours, length of hospital stay and 30-day readmission. Dexmedetomidine use significantly reduced postoperative in-hospital [1.23% vs. 4.59%; adjusted odds ratio (OR), 0.34; 95% confidence intervals (CI), 0.192 to 0.614; P < 0.0001], 30-day (1.76% vs. 5.12%; adjusted OR, 0.39; 95% CI, 0.226 to 0.655; P <0.0001) and 1-year (3.17% vs. 7.95%; adjusted OR, 0.47; 95% CI, 0.312 to 0.701; P = 0.0002) mortalities. Perioperative dexmedetomidine therapy also reduced the risk of overall complications (47.18 vs. 54.06%; adjusted OR, 0.80, 95% CI, 0.68 to 0.96; p= 0.0136) and delirium (5.46% vs. 7.42%; adjusted OR, 0.53; 95% CI, 0.37 to 0.75; p=0.0030). Conclusions Perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to one year and decreased incidence of postoperative complications and delirium in patients undergoing cardiac surgery.

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BackgroundAt present, sevoflurane inhalation anesthesia used on infants is well-known. But long-time exposure to inhalation anesthetic could cause neurologic disorder, especially nerve degeneration in infant and developing brain. The central nervous system degeneration of infants could affect the memory and cognitive function. γ-Aminobutyric acid (GABA) is a known inhibitory neurotransmitter in central nervous system. Inhalation anesthetic sevoflurane may activate GABAA receptor to inhibit central nervous system, leading to apoptosis of neural degeneration, cognitive dysfunction in the critical period of brain development.MethodsNeural stem cells were derived from Wistar embryos, cultured in vitro. Third generation of neural stem cells were randomly divided into four groups according to cultured suspension: Sevoflurane group (Group S), GABAA receptor antagonists, Bicuculline group (Group B), Sevoflurane + GABAA receptor antagonists, Bicuculline group (Group S + B), dimethyl sulphoxide (DMSO) group (Group D). Group B and Group D did not receive sevoflurane preconditioning. Group S and Group S + B were pretreated with 1 minimum alveolar concentration (MAC) sevoflurane for 0 h, 3 h, 6 h, and 12 h. Group S + B and Group B were pretreated with bicuculline (10 uM). Group D was treated with DMSO (10 uL/mL). After treatments above, all groups were cultured for 48 h. Then we measured the cells viability by Cell Counting Kit (CCK-8) assay, cytotoxicity by Lactate Dehydrogenase (LDH) assay, apoptosis ratio with Annexin V/propidium iodide (PI) staining by flow cytometry, and the expression of GABAAR, anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax and Caspase-3 by western blotting.ResultsAfter exposing to sevoflurane for 0 h, 3 h, 6 h, and 12 h with 1MAC, we found that cell viability obviously decreased and cytotoxicity increased in time-dependent way. And Annexin V/PI staining indicated increased apoptosis ratio by flow cytometry. The protein level of GABAA receptor, pro-apoptotic protein Bax and apoptosis protein Caspase-3 increased; while anti-apoptotic protein Bcl-2 decreased. And bicuculline could reverse all detrimental results caused by sevoflurane.ConclusionSevoflurane can inhibit the central nervous system by activating GABAA, resulting in apoptosis of neural stem cells, thus leading to the NSCs degeneration.

Purpose: For the topical anesthetic, transcriptional transactivator peptide (TAT) modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were prepared and then used for improving transdermal delivery of local anesthetic drug. Methods: In this study, TAT was conjugated with Distearoyl phosphatidylethanolamine-(polyethylene glycol) 2000 -maleimide (DSPE-PEG 2000 -Mal) to obtain TAT-PEG 2000 -DSPE. TAT-NLCs-LID were successfully prepared and characterized by determination of their particle size, morphology, drug encapsulation efficiency and in vitro drug release behavior. The skin permeation of LID-LNPs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro and in vivo anesthesia effect was evaluated on mice. Results:The results showed that TAT-NLCs-LID have substantially small mean diameter (157.9 nm) and high encapsulation efficiency (81.8%). From the in vitro skin permeation results, transdermal flux of TAT-NLCs-LID was about several times higher than that of LID solution and NLCs-LID. In vivo anesthesia effect evaluation illustrated that TAT-NLCs-LID can enhance the transdermal delivery of LID by reducing the pain threshold in mice. Conclusion: These results indicate that the novel TAT containing drug delivery system is very useful for overcoming the barrier function of the skin and could deliver anesthetic through the skin. TAT-NLCs-LID could function as promising topical anesthetic system.

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In order to investigate the effects of transient receptor potential channel A1 (TRPA1)-mediated neurogenic inflammatory reaction on the process of ventilator-induced lung injury (VILI). A rat VILI model was created, and the TRPA1 selective antagonist, HC-030031, was used to investigate the role of TRPA1 in the process of VILI. 50 rats were randomly divided into five groups: vehicle group, low tidal volume group, high tidal volume group, low tidal volume group with TRPA1 inhibitor, high tidal volume group with TRPA1 inhibitor. Biochemical index of lung injury in each group were determined, including the W/D ratio, total protein, count of WBC, content of MDA, activities of MPO and SOD, content of IL-8, TNF-α and substance P. Results showed that TRPA1 inhibitor could significantly reduce the inflammatory response and generation of reactive oxygen species, improve SOD activity and inhibit the production of inflammatory factors in lung tissues. TRPA1 was expressed in vagal nerve afferents, and the TRPA1 antagonist significantly inhibited the expression of substance P, indicating the involvement of TRPA1 in neurogenic inflammation. In conclusion, TRPA1 might be involved in the pathophysiological process of VILI by inducing the neurogenic inflammation, and TRPA1 inhibitor could inhibit inflammatory response of VILI.

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The study aimed to investigate the osteogenic ability of bioactive glass (bioglass) combined with recombinant human bone morphogenetic protein-9 (rhBMP-9) on rat bone marrow mesenchymal stem cells (BMSCs) in vitro. The study also compares bone regeneration using rhBMP9 soaked with different carrier systems, including bioglass or collagen membranes (BioGide, BG) in a rat alveolar bone site preservation model in vivo. Methods: Scanning electron microscopy was employed to analyze bioglass surface. The absorption and release potential of rhBMP9 from bioglass were researched by ELISA. The cell viability, adhesion, proliferation, and differentiation were assessed for rhBMP9 soaked on bioglass by cck-8 kit, alkaline phosphatase (ALP) activity assay, alizarin red staining, and real-time PCR. Furthermore, prepared grafts (bioglass þ BG, bioglass/rhBMP9þBG, and bioglass þ BG/rhBMP9) were implanted into the maxillary right first incisor sockets of Sprague Dawley rats for 8 weeks, and new bone formation was quantified by micro-CT and histological analysis. Results: Bioglass absorbed rhBMP9 dramatically and released it with a slow and stable speed within ten days by ELISA. When used with cck-8 kit detection, cell viability at 24 h, cell adhesion rate at 8 h, and cell proliferation at 1, 3, and 5 days were decreased in the bioglass alone group versus the control group but slightly increased with the addition of rhBMP9. Similarly, the effect of osteogenic differentiation on bioglass increased significantly when combined with rhBMP9 by upregulating the expression of ALP, mineralized matrix, and osteogenic related genes. Furthermore, both bioglass/rhBMP9þBG samples and bioglass þ BG/rhBMP9 samples significantly improved several bone formation parameters compared with bioglass þ BG samples. Interestingly, bioglass þ BG/rhBMP9 samples demonstrated more bone regeneration in rat site preservation models. Conclusions: Both bioglass and BG can be applied in GBR surgery as effective carriers of rhBMP9. However, BG may be more suitable than bioglass for investigating site preservation effect after tooth extraction when associated with rhBMP9 and provides a practical clinical solution to the problem of bone deficiency caused by alveolar bone atrophy.