ABSTRACT
BACKGROUND: Postoperative cognitive decline (PCD) requires microglial activation. Voltage-gated Kv1.3 potassium channels are involved in microglial activation. We determined the role of Kv1.3 in PCD and the efficacy and safety of inhibiting Kv1.3 with phenoxyalkoxypsoralen-1 (PAP-1) in preventing PCD in a mouse model. METHODS: After institutional approval, we assessed whether Kv1.3-deficient mice (Kv1.3-/-) exhibited PCD, evidenced by tibial-fracture surgery-induced decline in aversive freezing behaviour, and whether PAP-1 could prevent PCD and postoperative neuroinflammation in PCD-vulnerable diet-induced obese (DIO) mice. We also evaluated whether PAP-1 altered either postoperative peripheral inflammation or tibial-fracture healing. RESULTS: Freezing behaviour was unaltered in postoperative Kv1.3-/- mice. In DIO mice, PAP-1 prevented postoperative (i) attenuation of freezing behaviour (54 [17.3]% vs 33.4 [12.7]%; P=0.03), (ii) hippocampal microglial activation by size (130 [31] pixels vs 249 [49]; P<0.001) and fluorescence intensity (12 000 [2260] vs 20 800 [5080] absorbance units; P<0.001), and (iii) hippocampal upregulation of interleukin-6 (IL-6) (14.9 [5.7] vs 25.6 [10.4] pg mg-1; P=0.011). Phenoxyalkoxypsoralen-1 neither affected surgery-induced upregulation of plasma IL-6 nor cartilage and bone components of the surgical fracture callus. CONCLUSIONS: Microglial-mediated PCD requires Kv1.3 activity, determined by genetic and pharmacological targeting approaches. Phenoxyalkoxypsoralen-1 blockade of Kv1.3 prevented surgery-induced hippocampal microglial activation and neuroinflammation in mice known to be vulnerable to PCD. Regarding perioperative safety, these beneficial effects of PAP-1 treatment occurred without impacting fracture healing. Kv1.3 blockers, currently undergoing clinical trials for other conditions, may represent an effective and safe intervention to prevent PCD.
Subject(s)
Cognitive Dysfunction/prevention & control , Encephalitis/prevention & control , Kv1.3 Potassium Channel/antagonists & inhibitors , Postoperative Complications/prevention & control , Wound Healing/physiology , Animals , Disease Models, Animal , MiceABSTRACT
Objective To evaluate the efficacy of endobronchial intubation with double-lumen tube using fiberoptic bronchoscope assisted by video laryngoscope.Methods Thirty patients of both sexes,who underwent failed endobronchial intubation with double-lumen tube using direct laryngoscope,aged 25-64 yr,with body mass index of 23-34 kg/m2,were randomly divided into 2 groups (n=15 each) using a random number table:fiberoptic bronchoscope group (group F) and fiberoptic bronchoscope assisted by video laryngoscope group (group VF).The patients were intubated with double-lumen tube under the guide of fiberoptic bronchoscope in group F.The patients were intubated with double-lumen tube under the guide of fiberoptic bronchoscope assisted by video laryngoscope in group VF.The rate of successful intubation,intubation time,and glottis and epiglottis exposure condition when the video laryngoscope was used in group VF were recorded.The patients were followed up postoperatively,and the development of intubation-related complications (sore throat,hoarseness and swallowing difficulty) was also recorded.Results Compared with group F,the intubation time was significantly shortened,and the success rate of intubation at first attempt and second success rate of intubation were significantly increased in group VF (P＜0.05).There was no statistically significant difference in the incidence of intubation-related complications between the two groups (P＞0.05).Conclusion Video laryngoscope provides better efficacy for endobronchial intubation with double-lumen tube using fiberoptic bronchoscope.
ABSTRACT
BACKGROUND: Acellular bladder submucosa is a natural extracellular matrix, which is mainly composed of collagen Ⅰ and Ⅲ. It is regarded as an ideal biological scaffold material. OBJECTIVE: To evaluate the biocompatibility of acellular bladder submucosa as a tissue engineered scaffold material. METHODS: Pig urinary bladder was immersed in the solution of PBS and sodium azide for a night, and the mucosa was removed. Acellular bladder submucosa was prepared using continuous hypotension, freeze-thawed treatment and NaOH spallation. The biocompatibility of acellular bladder submucosa was evaluated through histologic structure, DNA residual, cytotoxicity, cell adhesion, as well as subcutaneous inflammatory reactions. RESULTS AND CONCLUSION: The cell components were completely eliminated after deoellularization treatment, while the extracellular matrix was remained intact as normal bladder:According to MTT results, cytotoxicity of acellular bladder matrix was assigned to be the first grade. No DNA signal was observed after extraction, and the matrix also supported porcine smooth muscle cell attachment and proliferation. Subcutaneous implantation of the matrix indicated that the acellular bladder submucosa trigger no immunologic rejection reaction obviously. The results demonstrated that: the acellular bladder submucosa prepared here exhibits excellent biocompatibility, which can be used as substitution in tissue-engineering field.
