Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways involved.

Impact of propofol and sevoflurane anesthesia on cognition and emotion in gastric cancer patients undergoing radical resection

BACKGROUND Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer.However,there is a debate concerning their differential effects on cognitive function,anxiety,and depression in patients undergoing this procedure.AIM To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function,anxiety,depression,and organ function in patients undergoing radical resection of gastric cancer.METHODS A total of 80 patients were involved in this research.The subjects were divided into two groups:Propofol group and sevoflurane group.The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment(LOTCA),and anxiety and depression were assessed with the aid of the self-rating anxiety scale(SAS)and self-rating depression scale(SDS).Hemodynamic indicators,oxidative stress levels,and pulmonary function were also measured.RESULTS The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group.Additionally,the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group.The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group.Moreover,the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group.CONCLUSION Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer.Propofol anesthesia has a minimal effect on patients'pulmonary function,consequently enhancing their postoperative recovery.Sevoflurane anesthesia causes less impairment on patients'cognitive function and mitigates negative emotions,leading to an improved postoperative mental state.Therefore,the selection of anesthetic agents should be based on the individual patient's specific circumstances.

Respiratory complications of propofol,sevoflurane,and dexmedetomidine anesthesia for fiberoptic bronchoscopy in children aged 1 month to 3 years:a randomized trial

Objective To evaluate the effect of propofol,sevoflurane,and dexmedetomidine on respiratory complications inchildren undergoing fiberoptic bronchoscopy(FOB).Methods This double-blind randomized clinical trial was conductedamong 120 children aged 1 month to 3 years undergoing FOB.The patients were randomized into 3 groups(n=40)foranesthesia induction with sevoflurane inhalation,1 mg/kg propofol,or 1μg/kg dexmedetomidine before bronchoscopy,andthe changes in hemodynamic parameters,sedation level,and respiratory complications during and after the procedure wereassessed.Results The patients'heart rate during bronchoscopy was significantly lower and the mean arterial blood pressuresignificantly higher in dexmedetomidine group than in sevoflurane and propofol groups(P<0.05).Cough duringbronchoscopy did not occur in any of the cases in propofol group,while the highest frequency of cough was recorded indexmedetomidine group.The incidence of laryngospasm in the propofol group(12.5%)was significantly lower than those insevoflurane and dexmedetomidine groups(30%and 32.5%,respectively)(P<0.05).Conclusion Sevoflurane and propofol aresafe and suitable for anesthesia induction in children below 3 years of age undergoing diagnostic FOB and can achieve bettersedative effect and lower the incidences of cough and respiratory complications as compared with dexmedetomidine.

Effects of sevoflurane on left ventricular function by speckletracking echocardiography in coronary bypass patients: A randomized trial

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography,and to assess the effect of sevoflurane on cardiac function.Sixty-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia(AS)group and a propofolbased total intravenous anesthesia(AA)group.The AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T1(after harvesting all grafts and before coronary anastomosis)and T_(2)(30 min after completing all coronary anastomoses)(P<0.05).Moreover,strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group,compared with the AA group at both T1 and T_(2)(P<0.01).The flow of the left internal mammary artery-left anterior descending artery graft was superior,and the postoperative concentration of troponin T decreased rapidly in the AS group,compared with the AA group(P<0.05).Compared with total intravenous anesthesia,sevoflurane resulted in a significantly higher global longitudinal strain,stroke volume,and cardiac output.Sevoflurane also led to an amelioration in the condition of the arterial graft.Furthermore,sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value.The findings need to be replicated in larger studies.

Does sevoflurane sedation in pediatric patients lead to“pseudo”leptomeningeal enhancement in the brain on 3 Tesla magnetic resonance imaging?

BACKGROUND Prominent leptomeningeal contrast enhancement(LMCE)in the brain is observed in some pediatric patients during sedation for imaging.However,based on clinical history and cerebrospinal fluid analysis,the patients are not acutely ill and do not exhibit meningeal signs.Our study determined whether sevoflurane inhalation in pediatric patients led to this pattern of‘pseudo’LMCE(pLMCE)on 3 Tesla magnetic resonance imaging(MRI).AIM To highlight the significance of pLMCE in pediatric patients undergoing enhanced brain MRI under sedation to avoid misinterpretation in reports.METHODS A retrospective cross-sectional evaluation of pediatric patients between 0-8 years of age was conducted.The patients underwent enhanced brain MRI under inhaled sevoflurane.The LMCE grade was determined by two radiologists,and interobserver variability of the grade was calculated using Cohen’s kappa.The LMCE grade was correlated with duration of sedation,age and weight using the Spearman rho rank correlation.RESULTS A total of 63 patients were included.Fourteen(22.2%)cases showed mild LMCE,48(76.1%)cases showed moderate LMCE,and 1 case(1.6%)showed severe LMCE.We found substantial agreement between the two radiologists in detection of pLMCE on post-contrast T1 imaging(kappa value=0.61;P<0.001).Additionally,we found statistically significant inverse and moderate correlations between patient weight and age.There was no correlation between duration of sedation and pLMCE.CONCLUSION pLMCE is relatively common on post-contrast spin echo T1-weighted MRI of pediatric patients sedated by sevoflurane due to their fragile and immature vasculature.It should not be misinterpreted for meningeal pathology.Knowing pertinent clinical history of the child is an essential prerequisite to avoid radiological overcalling and the subsequent burden of additional investigations.

Effects of Sevoflurane and Propofol on Neurological Recovery of Traumatic Brain Injury Patients in the Early Postoperative Stage: A Retrospective Cohort Study

Objective To investigate the effects of propofol and sevoflurane on neurological recovery of traumatic brain injury(TBI)patients in the early postoperative stage.Methods We retrospectively analyzed the clinical data of TBI patients who underwent craniotomy or decompressive craniectomy.Generalized additive mixed model(GAMM)was used to analyze effects of propofol and sevoflurane on Glasgow Coma Scale(GCS)on postoperative days 1,3,and 7.Multivariate regression analysis was used to analyze effects of the two anesthetics on Glasgow Outcome Scale(GOS)at discharge.Results A total of 340 TBI patients were enrolled in this study.There were 110 TBI patients who underwent craniotomy including 75 in the propofol group and 35 in the sevoflurane group,and 134 patients who underwent decompressive craniectomy including 63 in the propofol group and 71 in the sevoflurane group.It showed no significant difference in GCS at admission between the propofol and the sevoflurane groups among craniotomy patients(β=0.75,95%CI:-0.55 to 2.05,P=0.260).However,elevation in GCS from baseline was 1.73 points(95%CI:-2.81 to-0.66,P=0.002)less in the sevoflurane group than that in the propofol group on postoperative day 1,2.03 points(95%CI:-3.14 to-0.91,P 0.001)less on day 3,and 1.31 points(95%CI:-2.43 to-0.19,P=0.022)less on day 7.The risk of unfavorable GOS(GOS 1,2,and 3)at discharge was higher in the sevoflurane group(OR=4.93,95%CI:1.05 to 23.03,P=0.043).No significant difference was observed among two-group decompressive craniectomy patients in GCS and GOS.Conclusions Compared to propofol,sevoflurane was associated with worse neurological recovery during the hospital stay in TBI patients undergoing craniotomy.This difference was not detected in TBI patients undergoing decompressive craniectomy.

Sevoflurane Preconditioning and Total Knee Arthroplasty Bleeding: Randomized Controlled Trial

Background: Total knee arthroplasty (TKA) is a highly complex and effective surgery even though its perioperative bleeding may increase the need for blood transfusion and its associated infection risk, cardiovascular overload, increased costs, and mortality. As the tourniquet reduces intraoperative bleeding, it may be associated with postoperative bleeding, venous thrombosis, and distal ischemia. The reperfusion may trigger a local and systemic inflammatory response. Anesthetic preconditioning (APC) with sevoflurane minimizes ischemia-reperfusion syndrome (IRS). This study evaluated the effects of APC with sevoflurane on perioperative bleeding in TKA. Methods: We allocated 30 patients into two groups: a sevo group (sevoflurane 2% for 15 minutes before the tourniquet) and a control group (propofol infusion). Laboratory tests were collected right before the tourniquet (LAB PRE, in the operating room) and after its release at four moments: LAB POST (immediately after), LAB 2 (two hours after), LAB 12 (12 hours after), and LAB 24 (24 hours after). The volume of the suction drain was measured at one, two, 12, and 24 hours after the end of the surgery. Antifibrinolytics were not administered. Results: There was no statistically significant difference in bleeding-related variables, such as drained volume and hemoglobin and hematocrit measurements. Drainage volume was higher in the first two hours after the procedure, while hematocrit decreased pre- to postoperatively and between two and 12 hours post-procedure. Conclusion: Sevoflurane as an anesthetic preconditioning did not reduce postoperative bleeding in TKA surgery.

Protective effect of sevoflurane on lung function of elderly chronic obstructive pulmonary disease patients undergoing total hip arthroplasty

BACKGROUND Chronic obstructive pulmonary disease(COPD)is a common respiratory disorder that affects the elderly population and increases the risk of postoperative pulmonary complications(PPCs)after major surgeries.Sevoflurane is a volatile anesthetic that has been shown to have anti-inflammatory and antioxidant properties and attenuate lung injury in animal models.AIM To evaluate the protective effect of sevoflurane on the lung function of elderly COPD patients undergoing total hip arthroplasty(THA).METHODS In this randomized controlled trial,we randomly assigned 120 elderly patients with COPD,who were scheduled for THA,to receive either sevoflurane(sevoflurane group)or propofol(propofol group)as the maintenance anesthetic.The primary outcome was the incidence of PPCs within seven days after surgery.The secondary outcomes were changes in the lung function parameters,inflammatory markers,oxidative stress markers,and postoperative pain scores.RESULTS The results showed that the incidence of PPCs was significantly lower in the sevoflurane group than in the propofol group(10%vs 25%,P=0.02).Furthermore,the decline in the forced expiratory volume in 1 s,forced vital capacity,and peak expiratory flow was significantly lesser in the sevoflurane group than in the propofol group at 24 h and 48 h after surgery(P<0.05).The interleukin-6,tumor necrosis factor-alpha,malondialdehyde,and 8-hydroxy-2α-deoxyguanosine levels were significantly lower in the sevoflurane group than in the propofol group at 24 h after surgery(P<0.05).The sevoflurane group showed significantly lower postoperative pain scores than the propofol group at 6 h,12 h,and 24 h after surgery(P<0.05).CONCLUSION Sevoflurane protects the lung function of elderly COPD patients undergoing THA under general anesthesia by reducing the incidence of PPCs,attenuating inflammatory and oxidative stress responses,and alleviating postoperative pain.

Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore

Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.

Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 ~tg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 ~tg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spon- taneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100~ and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry （http：//www.chictr.org. cn/） （registration number： ChiCTR-IPR- 16008113）.

Effect of sevoflurane preconditioning on astrocytic dynamics and neural network formation after cerebral ischemia and reperfusion in rats

Astrocytes, the major component of blood-brain barriers, have presented paradoxical profiles after cerebral ischemia and reperfusion in vivo and in vitro. Our previous study showed that sevoflurane preconditioning improved the integrity of blood-brain barriers after ischemia and reperfusion injury in rats. This led us to investigate the effects of sevoflurane preconditioning on the astrocytic dynamics in ischemia and reperfusion rats, in order to explore astrocytic cell-based mechanisms of sevoflurane preconditioning. In the present study, 2,3,5-triphenyltetrazolium chloride staining and Garcia behavioral scores were utilized to evaluate cerebral infarction and neurological outcome from day 1 to day 3 after transient middle cerebral artery occlusion surgery. Using immunofluorescent staining, we found that sevoflurane preconditioning substantially promoted the astrocytic activation and migration from the penumbra to the infarct with microglial activation from day 3 after middle cerebral artery occlusion. The formation of astrocytic scaffolds facilitated neuroblasts migrating from the subventricular zone to the lesion sites on day 14 after injury. Neural networks increased in the infarct of sevoflurane preconditioned rats, consistent with decreased infarct volume and improved neurological scores after ischemia and reperfusion injury. These findings demonstrate that sevoflurane preconditioning confers neuroprotection, not only by accelerating astrocytic spatial and temporal dynamics, but also providing astrocytic scaffolds for neuroblasts migration to ischemic regions, which facilitates neural reconstruction after brain ischemia.

Sevoflurane plays a reduced role in cognitive impairment compared with isoflurane: limited effect on fear memory retention

Isoflurane and sevoflurane are both inhalation anesthetics,but in clinical application,sevoflurane has been considered to be less suitable for long-term anesthesia because of its catabolic compounds and potential nephrotoxicity.Nevertheless,recent studies have shown that these two inhalation anesthetics are similar in hepatorenal toxicity,cost,and long-term anesthetic effect.Moreover,sevoflurane possibly has less cognitive impact on young mice.In this study,C57BL/6 mice aged 8–10 weeks were exposed to 1.2%isoflurane or 2.4%sevoflurane for 6 hours.Cognitive function and memory were examined in young mice using the novel object recognition,contextual fear conditioning,and cued-fear extinction tests.Western blot assay was performed to detect expression levels of D1 dopamine receptor,catechol-O-methyltransferase,phospho-glycogen synthase kinase-3β,and total glycogen synthase kinase-3βin the hippocampus.Our results show that impaired performance was not detected in mice exposed to sevoflurane during the novel object recognition test.Contextual memory impairment in the fear conditioning test was shorter in the sevoflurane group than the isoflurane group.Long-term sevoflurane exposure did not affect memory consolidation,while isoflurane led to memory consolidation and reduced retention.Downregulation of hippocampal D1 dopamine receptors and phosphorylated glycogen synthase kinase-3β/total glycogen synthase kinase-3βand upregulation of catechol-O-methyltransferase may be associated with differing memory performance after exposure to isoflurane or sevoflurane.These results confirm that sevoflurane has less effect on cognitive impairment than isoflurane,which may be related to expression of D1 dopamine receptors and catechol-O-methyltransferase and phosphorylation of glycogen synthase kinase-3βin the hippocampus.This study was approved by the Institutional Animal Care and Use Committee,Nanjing University,China on November 20,2017(approval No.20171102).

Sevoflurane Versus Propofol for Myocardial Protection in Patients Undergoing Coronary Artery Bypass Grafting Surgery: a Meta-analysis of Randomized Controlled Trials

Objective To systematically review randomized controlled trials to compare myocardial protection profiles of sevoflurane with propofol in patients undergoing coronary artery bypass grafting （CABG） surgery. Methods Electronic databases were searched to identify all randomized controlled trials comparing sevoflurane with propofol for protecting myocardium in adult patients undergoing CABG surgery. Two authors independently extracted patients＇ perioperative data, including patients＇ baseline characteristics, surgical variables, and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference （WMD） and 95% confidential interval （C/）. For dichotomous data, treatment effects were calculated as odds ratio （OR） and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity （Q test P〈0.05）. Sensitivity analyses were done by examining the influence of statistical model on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P〈0.05. Results Our search yielded 13 studies including 696 patients, and 402 patients were allocated into sevoflurane group and 294 into propofol group. There was no significant difference in postoperative mechanical ventilation time, inotropic support, mortality, myocardial infarction, and atrial fibrillation between the two groups （all P〉0.05）. Patients randomized into sevoflurane group had higher post-bypass cardiac index （WMD=0.39, 95% CI： 0.18 to 0.60, P=0.0003）, lower troponin I level （WMD=-0.82, 95% CI：-0.87 to -0.85, P=0.0002）, lower incidence of myocardial ischemia （OR=0.37, 95% CI： 0.16 to 0.83, P=0.02）, shorter ICU and hospital stay length （WMD=-10.99, 95% CI： -12.97 to -9.01, P〈0.00001; WMD=-0.78, 95% CI： -1.00 to -0.56, P〈0.00001, respectively）. Conclusion This meta-analysis has found some evidence showing that sevoflurane has better myocardial protection than propofol in CABG surgery.

Effect of sevoflurane on tissue permeability of lung ischemia-reperfusion injury in rats

Objective:To investigate the effect of sevoflurane on tissue permeability of lung ischemiareperfusion injury(LIRI)in rats.Methods:A total of 45 wistar rats were randomly divided into3 groupsⅠ,Ⅱ,Ⅲ.Modified Eppinger method was adopted to establish the rat lung ischemiareperfusion injury model.GroupⅠserved as the control group,groupⅡas ischemia reperfusion group,groupⅢas sevoflurane ischemia-reperfusion group.Blood gas index,lung permeability index(LPI)change,lung tissue pathology change and lung water content were observed and compared between groups of rats at different time points.Results:During ischemia reperfusion,all rats kept balance of the MAP during different time points,SPO_2 of groupⅡandⅢdecreased significantly thanⅠgroup(P<0.05);after reperfusion lung permeability index in GroupⅡandⅢwas higher than the control group significantly(P<0.05),120 min after reperfusion LPI change and iujury of groupⅢwas significantly lower thanⅡgroup(P<0.05);interstitial and alveolar cavity effusion in of groupⅢwere lower than that of groupⅡ.Conclusions:Sevoflurane pretreatment can reduce the lung tissue permeability,and LIRI plays a protective role in LIRI.

Preventive effects of sevoflurane treatment on lung inflammation in rats

Objective:To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopolysaccharide-induced acute lung injury(ALI).Methods:The rat model of ALI was established by intratracheal instillation of lipopolysaccharide(LPS).45 infantile SD rats[body weight(272±15) g]were randomly divided into 3 groups(n=15):control group,LPS group, sevoflurane group.NS(1 mL/kg) was instillated in rats’airways of control group;LPS(5 mg/ kg) was instillated in rats’airways of LPS group.Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats’airways.Six hours after NS or LPS instillation,all rats were exsanguinated.Lung tissues were examined by HE staining.Expressions of TNF-αand ICAM1 mRNA were detected by semiquantitative RT-PCR techniques.The protein level of TNF-αand ICAM1 were assessed by western blot techniques.Results:In LPS group the permeability of lung tissues increased,organizational structure severely damaged and the alveolar wall turned thick,with interstitial edema and Europhiles infiltrated increasingly.The LPS group had higher mRNA expressions of TNF-αand ICAM1 than control group and sevoflurane group (P【0.05),and LPS group had higher protein level of TNF-αand ICAMI than control group and sevoflurane group(P【0.05).Conclusions:Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

Sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway:An experimental study

Objective:To study whether sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway.Methods:H9c2 myocardial cell lines were cultured and divided into control group(C group),hypoxia reoxygenation group(H/R group),sevoflurane pretreatment+hypoxia reoxygenation group(SP group) and sevoflurane combined with Compound C pretreatment+hypoxia reoxygenation group(ComC group),and the cell proliferation activity and apoptosis rate,myocardial enzyme levels in culture medium as well as the expression of apoptosis genes and p-AMPK in cells were determined.Results:p-AMPK expression in cells of H/R group was significantly lower than that of C group,SP group was significantly higher than that of H/R group;cell proliferation activity value and Bcl-2 expression in cells of H/R group were significantly lower than those of C group,SP group were significantly higher than those of H/R group,Com C group were significantly lower than those of SP group;apoptosis rate,LDH,CK and AST levels as well as the Bax and Caspase-3 expression in cells of H/R group were significantly higher than those of C group,SP group were significantly lower than those of H/R group,ComC group were significantly higher than those of SP group.Conclusions:Sevoflurane pretreatment can activate AMPK signaling pathway to inhibit the myocardial apoptosis caused by hypoxia reoxygenation.

Is longer sevoflurane preconditioning neuroprotective in permanent focal cerebral ischemia?

Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, followed by induction of perma- nent cerebral ischemia. Results demonstrated that 30- and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute se- voflurane preconditioning additionally reduced the number of TUNEL- and caspase-3-positive cells in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings in- dicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis.

Ca^(2+) cytochemical changes of hepatotoxicity caused by halothane and sevoflurane in enzyme-induced hypoxic rats

AIM： To investigat the relation between hepatotoxicity of halothane and sevoflurane and altered hepatic calcium homeostasis in enzyme-induced hypoxic rats. METHODS： Forty-eight rats were pretreated with phenobarbital and randomly divided into six groups （eight in each group） and exposed to O2/N2/1.2 MAC anesthetics for 1 h： normal control （NC）, 21% O2/79% N2; hypoxic control （HC）, 14% O2/86% N2; normal sevoflurane （NS）, 21% O2/ N2/1.2MAC sevoflurane; hypoxic sevoflurane （HS）, 14% O2/N2/1.2MAC sevoflurane; normal halothane （NH）21%O2/79%N2/1.2MAC halothane; hypoxic halothane （HH）, 14%O2/N2/1.2MAC halothane. Liver specimens and blood were taken 24 h after exposure to calcium and determined by EDX microanalysis. RESULTS： The liver of all rats given halothane （14% O2） had extensive centrilobular necrosis and denaturation. Morphologic damage was accompanied with an increase in serum glutarnic pyruvic transminase. In groups NH and HH, more calcium was precipitated in cytoplasm and mitochondria. CONCLUSION： These results suggest that halothane increases cytosolic Ca^2＋ concentration in hepatocytes. Elevation in Ca^2＋ concentration is implicated in the mechanism of halothane-induced hepatotoxicity. sevoflurane is less effective in affecting hepatic calcium homeostasis than halothane.

Enriched environment for offspring improves learning and memory impairments induced by sevoflurane exposure during the second trimester of pregnancy

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and memory of offspring.Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and memory of rat offspring remains unclear.In this study,rats at 14 days of pregnancy were exposed to 3.5%sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days.We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue,increased hippocampal neurogenesis,inhibited glycogen synthase kinase 3βactivity,and increased the expression of cell proliferation-relatedβ-catenin and apoptosis-related Bcl-2,indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus.These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and memory of offspring.This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018PS07K)on January 2,2018.

High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

Sevoflurane is the most commonly used volatile anesthetic during pregnancy.The viability of neural stem cells directly affects the development of the brain.However,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem cells.Therefore,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral abnormalities.On gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 hours.The offspring were weaned at 28 days and subjected to the Morris water maze test.The brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day（P） 0,14 and 28.Vascular endothelial growth factor（VEGF） and phosphoinositide 3-kinase（PI3 K）/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot assay.Exposure to high-concentration（3.5%） sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing times.At 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling（TUNEL）-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the offspring.At 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT（p-AKT） levels were decreased in the fetal brain.These changes were not observed in animals given low-concentration（2%） sevoflurane exposure.Together,our findings indicate that exposure to a high concentration of sevoflurane（3.5%） in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring.