Role of TRPM2 in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats / 中华麻醉学杂志

Objective:To evaluate the role of transient receptor potential melastatin2 (TRPM2) in sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.Methods:Sixty SPF-grade healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group M) and sevoflurane anesthesia+ TRPM2 inhibitor group (group M+ A). M and M+ A groups inhaled 2% sevoflurane for 5 h. In group M+ A, TRPM2 inhibitor ACA 20 mg/kg was intraperitoneally injected at 1 h before sevoflurane inhalation, and the equal volume of dimethyl sulfoxide was intraperitoneally injected in group C and group M. Morris water maze test was performed at 1 day after sevoflurane anesthesia. The escape latency, times of crossing the original platform and time spent in the original platform quadrant were collected. The expression of TRPM2 and necroptosis-related proteins (mixed lineage kinase domain-like protein [MLKL], receptor-interacting protein kinase-1 [RIPK1], phosphorylated MLKL [p-MLKL], and phosphorylated RIPK1 [p-RIPK1]) was detected by Western blot. The cytosolic Ca 2+ concentration in and necroptosis rate of hippocampal neurons were determined by flow cytometry. Results:Compared with group C, the escape latency was significantly prolonged, the times of crossing the original platform were decreased and the time spent in the original platform quadrant was shortened, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was up-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were increased in group M and group M+ A ( P<0.05). Compared with group M, the escape latency was significantly shortened, the times of crossing the original platform were increased, and the time spent in the original platform quadrant was prolonged, the expression of TRPM2, MLKL, RIPK1, p-MLKL and p-RIPK1 was down-regulated, and the cytosolic Ca 2+ concentrations in hippocampal neurons and necroptosis rate of hippocampal neurons were decreased in group M+ A ( P<0.05). Conclusions:Hippocampal TRPM2 is involved in the process of sevoflurane anesthesia-induced necroptosis in hippocampal neurons of aged rats.

Cardioprotection induced by sevoflurane postconditioning in patients undergoing cardiac surgery with cardiopulmonary bypass: a meta-analysis / 中华麻醉学杂志

Objective To systematically review the cardioprotection induced by sevoflurane postconditioning in the patients undergoing cardiac surgery with cardiopulmonary bypass.Methods Databases including Pubmed,EMBase,Web of Science,Cochrane Library,CBM,WangFang Data,CNKI and VIP were searched by a computer from the date of database establishment up to February 2019 and there was no limitation for language.The randomized control trials involving the cardioprotection induced by sevoflurane postconditioning in the patients undergoing cardiac surgery with cardiopulmonary bypass were collected.Evaluation indexes included:incidence of perioperative cardiac events,duration of intensive care unit stay,plasma concentrations of cardiac troponin I and creatine kinase-MB at 6 and 24 h after aortic opening,plasma concentrations of interleukin-6 at 2,12 and 24 h after aortic opening and percentage of spontaneous recovery of heart beat.Meta-analysis was conducted using the RevMan 5.3 and Stata 12.0 softwares.Results Seventeen randomized controlled trials involving 763 patients were included in our meta-analysis.Compared with control group,the incidence of reperfusion arrhythmia was decreased,the plasma concentrations of cardiac troponin I and creatine kinase-MB at 6 and 24 h after aortic opening and interleukin-6 at 2,12,and 24 h after aortic opening were decreased,the percentage of spontaneous recovery of heart beat was increased (P＜0.05 or 0.01),and no significant change was found in duration of intensive care unit stay in sevoflurane postconditioning group (P ＞ 0.05).Conclusion Sevoflurane postconditioning can produce cardioprotection in the patients undergoing cardiac surgery with cardiopulmonary bypass.

Effects of sevoflurane on hippocampal neurogenesis in dentate gyrus of mice of different ages / 中华麻醉学杂志

Objective To evaluate the effects of sevoflurane on hippocampal neurogenesis in den-tate gyrus (DG) of mice of different ages. Methods Ninety-six SPF healthy male C57BL∕6 mice, aged 2 weeks, 6 weeks, 9 months and 20 months (24 mice for each age, 12 mice for each group), were divided into 2 groups (n＝48 each) using a random number table method: control group (group C) and sevoflurane group (group S). Group S inhaled 3. 0% sevoflurane for 2 h once a day for 3 consecutive days, while group C inhaled the mixture of air and O2. Six mice of each age were selected, and 5′-bromo-2′-deoxyuridine (BrdU) 50 mg∕kg was intraperitoneally injected immediately before and after inhalation once a day for 3 consecutive days in two groups. Mice were sacrificed at 24 h after the last inhalation (T1), brains were re-moved and hippocampi isolated for determination of the number of nestin and doublecortin ( DCX) positive cells in DG by immunohistochemistry. Mice were sacrificed at 4 weeks after the last inhalation ( T2), brains were removed and hippocampi isolated for determination of the number of neuronal nuclei antigen (NeuN)∕BrdU and glial fibrillary acid protein ( GFAP )∕BrdU positive cells by immunofluorescence. Re-sults Compared with group C, the number of nestin and DCX positive cells was significantly reduced at T1, and the number of NeuN∕BrdU and GFAP∕BrdU positive cells was reduced at T2in mice of 2 weeks and 20 months old (P＜0. 05), and no significant change was found in the indices mentioned above in mice of 6 weeks and 9 months old in group S ( P＞0. 05). Conclusion Three percent sevoflurane can inhibit hipp-ocampal neurogenesis in DG of immature and old mice and exerts no influence on hippocampal neurogenesis in DG of juvenile and adult mice.

Role of autophagosomes clearance in delayed cardioprotection in rats with ischemia-reperfusion injury by sevoflurane preconditioning in vivo / 中华急诊医学杂志

Objective To evaluate role of autophagosomes clearance in delayed cardioprotection by sevoflurane preconditioning in rats with ischemia-reperfusion injury in vivo.Methods Forty-five adult male Sprague-Dawley rats,weighing 270-350 g,were randomly (random number) divided into 3 groups:sham operation group (sham group),ischemia-reperfusion group (CON group),sevoflurane preconditioning group (SWOP group).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by reperfusion for 2 h,and myocardial infarct size was stained by triphenyltetrazolium chloride.Cardiomyocyte apoptosis was evaluated by terminal deoxyribonucleotidyl transferase-mediated biotin-16dUTP nick-end labeling.Autophagosomes were detected under transmission electron microscope.Expression of LC3-Ⅱ,cathepsin B,p62 and cleaved caspase-3 were assessed by western blotting.Statistical analysis were performed using one or two way analysis of variance (SPSS 15.0,Chicago,USA) test followed by Dunnet-t or LSD-t test.Results Sevoflurane preconditioning reduced myocardial infarct size and the number of autophagosomes (P =0.027),attenuated cardiomyocyte apoptosis (P =0.042).Sevoflurane preconditioning decreased the level of LC3-Ⅱ (P =0.033),p62 (P =0.041)and cleaved caspase-3 (P =0.037),but increased the level of cathepsin B (P =0.046).Conclusions Delayed cardioprotection by sevoflurane preconditioning increased myocardial clearance of autophagosomes against the delayed ischemia reperfusion injury.

Effect of hyperlipidemia on pulmonary uptake in patients inhaling sevoflurane for anesthesia / 中华麻醉学杂志

Objective To evaluate the effect of hyperlipidemia on pulmonary uptake in the patients inhaling sevoflurane for anesthesia.Methods A total of 103 patients of both sexes,aged 20-50 yr,with body mass index of 18-25 kg/m2,of American.Society of Anesthesiologists physical status Ⅰ or Ⅱ,undergoing elective operation under general anesthesia,were enrolled in the study.Anesthesia was induced with iv midazolam 0.1 mg/kg,vecuronium 0.1 mg/kg,fentanyl 0.l mg/kg and etomidate 0.3 mg/kg.Patients were mechanically ventilated after endotracheal intubation.Patients inhaled 2％ sevoflurane for 30 min at an oxygen flow rate of 2 L/min.The inspired concentrations (Fi) and expired concentrations (Fe,Fe≈alveolar concentration [Fa]) of sevoflurane were recorded at 1,3,5,7,10,15,20 and 30 min of inhalation (T0-7).Patients were divided into either control group group C) or hyperlipidemia group (group H) according to the results of blood lipid levels after the end of observation.The ratio of Fa/Fi and time spent in reaching the titration value (Fa/Fi =0.8) were calculated in each group.Results There were 67 cases in group C and 36 cases in group H.Compared with group C,the Fa/Fi ratio was significantly decreased at 5,7 and 10 min of inhalation,and the time spent in reaching the titration value was prolonged in group H (P ＜ 0.05).Conclusion The pulmonary uptake of sevoflurane is increased,which may be associated with increased blood/gas partition coefficient.

Effect of sevoflurane postconditioning on inositol-requiring enzyme 1 signaling pathway in brain tissues in a rat model of hemorrhagic shock and resuscitation / 中华麻醉学杂志

Objective To evaluate the effect of sevoflurane postconditioning on inositol-requiring enzyme 1 (IRE1) signaling pathway in the brain tissues in a rat model of hemorrhagic shock and resuscitation (HSR).Methods Sixty healthy adult male Sprague-Dawley rats,weighing 300-350 g,were divided into 5 groups (n =12 each) using a random number table:sham operation group (group Sham),group HSR,1.2％ sevoflurane postconditioning group (group SP1),2.4％ sevoflurane postconditioning group (group SP2) and 3.6％ sevoflurane postconditioning group (group SP3).Hemorrhagic shock was induced by withdrawing blood (40％ of the total blood volume) from the right common carotid artery over an interval of 30 min,and 1 h later the animals were resuscitated with the shed blood infused via the left jugular vein over 30 min.SP1,SP2 and SP3 groups inhaled 1.2％,2.4％ and 3.6％ sevoflurane,respectively,for 30 min starting from the beginning of infusion of the shed blood.Oxygen was inhaled for 30 min instead of sevoflurane in Sham and HSR groups.Mean arterial pressure was recorded before withdrawing blood (T0),immediately after the end of withdrawing blood (T1),at 30 min after the end of withdrawing blood (T2),before infusion of the shed blood (T3),and immediately after infusion of the shed blood (T4).Arterial blood samples were obtained at T0,T1,T3 and T4 for blood gas analysis.Morris water maze test was performed at 72 h after the end of infusion of the shed blood.The animals were then sacrificed,and brains were removed for determination of the expression of caspase-3 in hippocampal CA1 region (by immunohistochemistry) and expression of IRE1 and X-box binding protein 1 (XBP1) in hippocampal tissues (by Western blot).Results Compared with group Sham,mean arterial pressure was significantly decreased at T1-3,the pH value and base excess were decreased,lactic acid concentrations were increased,the escape latency was prolonged,the frequency of crossing the original platform was decreased,and the expression of caspase-3 in hippocampal CA1 regitn and IRE1 and X BP 1 in hippocampal tissues was up-reg ulated in group HSR (P＜0.05).Compared with group HSR,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,and the expression of caspase-3 in hippocampal CA1 region and IRE1 and XBP1 in hippocampal tissues was down-regulated in SP2 and SP3 groups (P＜0.05),and no significant changes were found in the parameters mentioned above in group SP1 (P＞0.05).Conclusion The mechanism by which sevoflurane postconditioning reduces brain injury may be related to activating IRE1 signaling pathway in the brain tissues in a rat model of HSR.

Nuclear factor-κB signaling pathway and autophagy in inhaled sevoflurane-produced delayed myocardial protection in rats / 中华麻醉学杂志

Objective To evaluate nuclear factor (NF)-κB signaling pathway and autophagy in inhaled sevoflurane-produced delayed myocardial protection in rats.Methods Ninety-six adult male Sprague-Dawley rats,weighing 270-350 g,were randomly assigned into 6 groups (n =16 each):sham operation group (group S),ischemia-reperfusion (I/R) group,sevoflurane group (SEVO group),specific NF-κB inhibitor parthenolide (PTN)group,dimethyl sulfoxide (DMSO) group and PTN + sevoflurane group (PTN + SEVO group).The animals were anesthetized with intraperitoneal pentobarbital 50 mg/kg,intubated and mechanically ventilated.Myocardial I/R was induced by 30 min of occlusion of the left anterior descending branch of coronary artery followed by 2 h of reperfusion.In group I/R,33％ oxygen was inhaled for 2 h.In group SEVO,2.5％ sevoflurane was inhaled for 2 h.In groups PTN and DMSO,PTN 500 μg/kg and DMSO were administered intraperitoneally 15 min before oxygen inhalation respectively.In group PTN + SEVO,PTN 500 μg/kg was administered intraperitoneally 15 min before exposure to sevoflurane.Myocardial I/R was induced 24 h after intraperitoneal administration.Eight animals in each group were sacrificed immediately before ischemia and the hearts were removed to detect the NF-κB activity and expression of LC3-Ⅱ and cathepsin B.The left animals in each group were sacrificed at 2 h of reperfusion and the hearts were removed to determine the myocardial infarct size (by TTC staining).Results Compared with group S,the myocardial infarct size was significantly increased at 2 h of reperfusion in the other groups,and the NF-κB activity was significantly increased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately before ischemia in group SEVO (P ＜ 0.05).Compared with group I/R,the NF-κB activity was significantly increased and the expression of LC3-Ⅱ and cathepsin B was up-regulated immediately before ischemia,and the myocardial infarct size was significantly reduced at 2 h of reperfusion in group SEVO (P ＜ 0.05).Compared with group SEVO,the NF-κB activity was significantly decreased and the expression of LC3-Ⅱ and cathepsin B was down-regulated immediately before ischemia,and the myocardial infarct size was significantly increased at 2 h of reperfusion in DMSO,PTN and PTN + SEVO groups (P ＜ 0.05).Conclusion NF-κB signaling pathway and autophagy are involved in inhaled sevoflurane-produced delayed nyocardial protection in rats.

Comparison of effects of different anesthesia on immunologic function during perioperative radical mastectomy in patients having undergone preoperative chemotherapy / 中华麻醉学杂志

Objective To compare the effects of different anesthesia on immunologic function during perioperative radical mastectomy in patients having undergone preoperative chemotherapy. Methods Sixty ASA Ⅰ or Ⅱ patients, aged 28-64 yr, weighing 55-70 kg, scheduled for radical mastectomy, were studied. Thirty patients received preoperative chemical therapy for 3-4 weeks were randomly divided into CP group and CS group ( n = 15 each); thirty patients received no chemical therapy were also randomly divided into NCP group and NCS group (n=15 each).Propofol at a rate of 4-6 mg·kg-1·h-1 was infused in group CP and CS and sevoflurane with the end-tidal concentration of 1.5%-2.5% inhaled in group NPC and NCS to maintain anesthesia. Peripheral venous blood samples were taken before chemical therapy, before anesthesia, immediately after operation and at 72 h after operation for determination of the levels of T lymphocyte subsets and NK cells and plasma CK19 mRNA expression (by RT-PCR). CD4+/CD8+ ratio and the micrometastatic rate of the tumor cells were calculated. Results The CD3+ , CD8+ and NK cell level were significantly lower before anesthesia, immediately after operation and at 72 h after operation than before chemical therapy ( P < 0.05). The CD8+ immediately after operation and NK cell level at 72 h after operation in group CP, and CD4+ and NK cell levels immediately and at 72 h after operation in group CS were significantly lower than those before anesthesia ( P < 0.05). CD4+ and NK cell levels immediately and at 72 h after operation were significantly lower in group CS than in group CP, and in group NCS than in group NCP (P < 0.05). The CD4+/CD8+ ratio was significantly lower immediately after operation in group CS than in group CP ( P < 0.05) .There was no significant difference in the micrometastatic rate of the tumor cells among all groups (P > 0.05). Conclusion Sevoflurane combined anesthesia has a stronger inhibitory effect on immunologic function in radical mastectomy patients with preoperative chemotherapy than propofol combined anesthesia.

Comparación del efecto cardioprotector del preacondicionamiento farmacológico con anestésicos halogenados: sevoflurano versus isoflurano in vivo / Comparison of the cardioprotective effect of pharmacological preconditioning with halogenated anaesthetic agents: sevofluorane vs isofluorane in vivo

Fundamento: los anestésicos halogenados inducen preacondicionamiento y se utilizan en cirugía cardíaca. Muestran diferente poder preacondicionador, lo que se adjudica en parte a sus propiedades fisicoquímicas, al modelo animal utilizado y a su uso en distintas concentraciones. Objetivo: generar estrategias aplicables de protección frente al daño isquemia-reperfusión miocárdica. Comparar el efecto preacondicionador de sevoflurano e isoflurano in vivo. Material y método: estudiamos cuatro grupos de seis ratas cada uno (n = 24). Se utilizó un modelo en rata Wistar de isquemia-reperfusión miocárdica mediante infarto por ligadura de la arteria coronaria izquierda. Se realiza monitoreo hemodinámico y electrocardiograma (ECG) continuo, tinción histológica de área de infarto y en riesgo de infarto. El preacondicionamiento isquémico se realizó mediante ligadura seriada intermitente de la arteria coronaria izquierda previa al episodio de infarto de 30 minutos de duración; el preacondicionamiento farmacológico se realiza por exposición intermitente a halogenados previo a evento de infarto: 1 MAC de isoflurano y sevoflurano. Se comparan resultados con control. Resultados: se expresan como porcentaje del área de infarto isquémico (15,8±3,1); sevoflurano (21,8±1,3); isoflurano (28,3±1,3). Punta-control (41,3±2,0); preacondicionamiento en relación con el área de riesgo de infarto (media ± desvío estándar). Las zonas donde fue más evidente el fenómeno fueron: centro-control (33,7±2,2); preacondicionamiento isquémico (18,5±1,4); sevoflurano (26,5±1,9); isoflurano (33,9±2,3). Hubo significación con p<0,05 (ANOVA - Bonferroni) para todos los grupos entre sí. Conclusiones: el sevoflurano fue más efectivo que el isoflurano en la protección frente al daño por isquemia reperfusión. El preacondicionamiento isquémico mostró mayor protección que ambos halogenados.

Background: halogenated anesthetics induce preconditioning and are used in cardiac surgery. They show different preconditioning effect, in part due to their distinct physical and chemical properties, animal model chosen and different concentrations, utilized.Objectives: To develop applicable strategies of myocardial protection against ischemia-reperfusion injury. To compare the preconditioning effect of sevoflurane and isoflurane in vivo. Methods: four groups of 6 Wistar rats each (n=24) were studied using a myocardial ischemia-reperfusion model with infarct produced by occlusion of the left coronary artery. Continuous hemodynamic and electrocardiographic monitoring, and histological staining of infarct and at-risk areas were performed. Ischemic preconditioning was performed by intermittent serial occlusion of the left coronary artery before the 30-minute infarct occlusion; pharmacological preconditioning was performed by intermittent exposure to volatile anesthetic before the infarct: 1 Minimal Alveolar Concentration of isoflurane and sevoflurane. Results were compared with control. Results: they are expressed as percentage of infarct area in relation to area at risk (mean ± standard deviation). Preconditioning was more evident in these areas: center- control (33,7±2,2); ischemic preconditioning (15,8±3,1); sevoflurane (21,8±1,3); isoflurane (28,3±1,3). apex- control (41,3±2,0); ischemic preconditioning (18,5±1,4); sevoflurane (26,5±1,9); isoflurane (33,9±2,3). Statistically significant differences were found between all groups with p<0.05 (ANOVA-Bonferroni). Conclusions: sevoflurane was more effective than Isoflurane in protecting against ischemia reperfusion injury. Ischemic preconditioning prove to be more protective than both halogenated anesthetics.