Use of a rat model to characterize 35 arterial pulse wave parameters in a comparative study of isoflurane and Zoletil/ xylazine anesthesia and the effect of Acanthopanax senticosus extract

Background : Information obtained from arterial pulse waveforms (APW) can be usefulfor characterizing the cardiovascular system. To achieve this, it is necessary to know thedetailed characteristics of APWs in different states of an organism, which would allowAPW parameters (APW- Ps) to be assigned to particular (patho)physiological conditions.Therefore, our work aimed to characterize 35 APW- Ps in rats under the influence ofisoflurane (ISO) and Zoletil/xylazine (ZO/XY) anesthesia and to study the effect of rootextract from Acanthopanax senticosus (ASRE) in these anesthetic conditions.Methods : The right jugular vein of anesthetized rats was cannulated for the administrationof ASRE and the left carotid artery for the detection of APWs from which 35APW- Ps were evaluated.Results : We obtained data on 35 APW- Ps, which significantly depended on the anesthesia,and thus, they characterized the cardiovascular system under these two conditions.ASRE transiently modulated all 35 APW- Ps, including a transient decrease insystolic and diastolic blood pressure (BP) and heart rate or increases in pulse BP, d P /d t max , and systolic and diastolic areas. Whereas the transient effects of ASRE weresimilar, the extract had prolonged disturbing effects on the cardiovascular system inrats under ZO/XY but not under ISO anesthesia. This negative effect can result fromthe disturbance caused by ZO/XY anesthesia on the cardiovascular system.Conclusions : We characterized 35 APW- Ps of rats under ISO and ZO/XY anesthesiaand found that ASRE contains compounds that can modulate the properties of thecardiovascular system, which significantly depended on the status of the cardiovascularsystem. This should be considered when using ASRE as a nutritional supplementby individuals with cardiovascular problems.

ISOFLURANE REDUCES THE SYNTHESIS OF SURFACTANT-RELATED PROTEIN A OF ALVEOLAR TYPE II CELLS INJURED BY H_2O_2

Objective To explore the influence of isoflurane(Iso) on the synthesis of surfactant-related protein(SP-A) of alveolar type II cells(AT II cells) cultured in primary and injured by hydrogen peroxide(H2O2).Methods AT II cells were isolated from adult SD rats and used for experiments after 32h in primary culture and randomized into six groups: control group,0.28 mM Iso group,2.8mM Iso group,75 μM H2O2 group,75 μM H2O2 +0.28 mM Iso group and 75 μM H2O2 +2.8 mM Iso group. Each group was continuously incubated for 3 h after administration of Iso or/and H2O2. The intracellular SP-A and the SP-A of cultured medium were measured with an enzyme-linked immunosorbent assay(ELISA).Results Iso significantly decreased SP-A content of cultured medium and the intracellular,and aggravated the decrease of SP-A content induced by H2O2 in a dose-dependent manner.Conclusion Iso itself may decrease SP-A synthesis of AT II cells in vitro,and aggravate the damage of AT II cells especially under peroxidation condition.

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).

Ginsenoside Rb1 Attenuates Isoflurane/surgery-induced Cognitive Dysfunction via Inhibiting Neuroinflammation and Oxidative Stress

Objective Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress. Methods Five-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA. Results Here we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus. Conclusion These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

Effect of emulsified isoflurane on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytes

Objective:To explore the effect of emulsified isoflurane(EI)on apoptosis of anoxia-reoxygenation neonatal rat cardiomyocytea and relevant protein expression.Methods:Cardiac muscle anoxiareoxygenation damage model was established with culture in vitro neonatal rat cardiomyocytes.The cardiomyocytes were divided into control group,model group,fat emulsion group and EI group.The cardiomyocytes apoptosis rates and lactic dehydrogenase(LDH),superoxide dismutase(SOD)and malondialdehyde(MDA)index standardization were detected after relevant treatment The expression of apoptosis-related proteins Bel-2,Bax and Caspase-3 were detected with Western blot approach.Results:After hypoxia/reoxygenation(H/R)model was treated by EI,the cells apoptosis rate decreased and was dramatically below the fat emulsion group(P<0.05),Cardiomyocytes biochemical index detection presented that,compared with the control group that the LDH activity and MDA content dramatically increased(P<0.05),while the SOD activity notably decreased(P<0.05);compared with the H/R group,the SOD activity of the fat emulsion group and EI group increased(P<0.05);while the LDH activity and MDA content decreased(P<0.05).And the change of the EI group was more remarkable than the fat emulsion group(P<0.05).The Western blot analysis presented that,compared with the control group,the Bcl-2 protein expression of the other groups significantly decreased(P<0.05),the expressions of Bax protein and Caspase-3protein increased significantly(P<0.05);compared with H/R group,cardiomyocytes Bc1-2protein expression of EI group increased significantly(P<0.05),the expressions of Bax protein and Caspase-3 protein decreased significantly(P<0.05),and the change of EI group was more remarkable than the fat emulsion group(P<0.05).Conclusions:EI can inhabit the apoptosis of anoxia-reoxygenation damage model cardiomyocytes,and may he related to the up-regulation of expression of Bcl-2 and down-regulation of expression of Caspase-3 protein.

GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice

Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment.GLYX-13(rapastinel)acts on the glycine site of N-methyl-D-aspartate receptors(NMDARs)and has been shown to enhance hippocampus-dependent learning and memory function.However,the mechanisms by which GLYX-13 affects learning and memory function are still unclear.In this study,we investigated these mechanisms in a mouse model of long-term anesthesia exposure.Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure(1.5%for 6 hours).Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test.The mRNA expression and phosphorylated protein levels of NMDAR pathway components,N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca^2+/calmodulin dependent protein kinaseⅡ(CaMKII)-cyclic adenosine monophosphate response element binding protein(CREB),in the hippocampus were evaluated by quantitative RT-PCR and western blot assay.Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B,CaMKII and CREB mRNA and phosphorylated protein levels.Intracerebroventricular injection of KN93,a selective CaMKII inhibitor,significantly diminished the effect of GLYX-13 on cognitive function and NR2B,CaMKII and CREB levels in the hippocampus.Taken together,our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus.Therefore,GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction.This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November 20,2017.

Inhibition of α5 GABAA receptors has preventive but not therapeutic effects on isoflurane-induced memory impairment in aged rats

The α5 subunit-containing gamma-amino butyric acid type A receptors(α5 GABAARs) are a distinct subpopulation that are specifically distributed in the mammalian hippocampus and also mediate tonic inhibitory currents in hippocampal neurons. These tonic currents can be enhanced by low-dose isoflurane, which is associated with learning and memory impairment. Inverse agonists of α5 GABAARs, such as L-655,708, are able to reverse the short-term memory deficit caused by low-dose isoflurane in young animals. However, whether these negative allosteric modulators have the same effects on aged rats remains unclear. In the present study, we mainly investigated the effects of L-655,708 on low-dose(1.3%) isoflurane-induced learning and memory impairment in elderly rats. Young(3-month-old) and aged(24-month-old) Wistar rats were randomly assigned to receive L-655,708 0.5 hour before or 23.5 hours after 1.3% isoflurane anesthesia.The Morris Water Maze tests demonstrated that L-655,708 injected before or after anesthesia could reverse the memory deficit in young rats. But in aged rats, application of L-655,708 only before anesthesia showed similar effects. Reverse transcription-polymerase chain reaction showed that low-dose isoflurane decreased the mRNA expression of α5 GABAARs in aging hippocampal neurons but increased that in young animals. These findings indicate that L-655,708 prevented but could not reverse 1.3% isoflurane-induced spatial learning and memory impairment in aged Wistar rats. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Academy of Military Medical Science of China(approval No. NBCDSER-IACUC-2015128) in December 2015.

An appropriate level of autophagy reduces emulsified isoflurane-induced apoptosis in fetal neural stem cells

Autophagy plays essential roles in cell survival.However,the functions and regulation of the autophagy-related proteins Atg5,LC3B,and Beclin 1 during anesthetic-induced developmental neurotoxicity remain unclear.This study aimed to understand the autophagy pathways and mechanisms that affect neurotoxicity,induced by the anesthetic emulsified isoflurane,in rat fetal neural stem cells.Fetal neural stem cells were cultured,in vitro,and neurotoxicity was induced by emulsified isoflurane treatment.The effects of pretreatment with the autophagy inhibitors 3-methyladenine and bafilomycin and the effects of transfection with small interfering RNA against ATG5(siRNA-Atg5)were observed.Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,and apoptosis was assessed using flow cytometry.Ultrastructural changes were analyzed through transmission electron microscopy.The levels of the autophagy-related proteins LC3B,Beclin 1,Atg5,and P62 and the pro-apoptosis-related protein caspase-3 were analyzed using western blot assay.The inhibition of cell proliferation and that of apoptosis rate increased after treatment with emulsified isoflurane.Autophagolysosomes,monolayer membrane formation due to lysosomal degradation,were observed.The autophagy-related proteins LC3B,Beclin 1,Atg5,and P62 and caspase-3 were upregulated.These results confirm that emulsified isoflurane can induce toxicity and autophagy in fetal neural stem cells.Pre-treatment with 3-methyladenine and bafilomycin increased the apoptosis rate in emulsified isoflurane-treated fetal neural stem cells,which indicated that the complete inhibition of autophagy does not alleviate emulsified isoflurane-induced fetal neural stem cell toxicity.Atg5 expression was decreased significantly by siRNA-Atg5 transfection,and cell proliferation was inhibited.These results verify that the Atg5 autophagy pathway can be regulated to maintain appropriate levels of autophagy,which can inhibit the neurotoxicity induced by emulsified isoflurane anesthetic in fetal neural stem cells.

Molecular mechanisms and the role of the protein kinase pathway in rat spatial memory impairment following isoflurane anesthesia

BACKGROUND: Animal experiments have demonstrated that isoflurane exposure alone induces learning and memory deficits for weeks or months. However, the molecular mechanisms of learning and memory remain poorly understood. Hippocampal expression of calcium/phospholipid- dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA) in rats have been shown to be associated with memory processing. OBJECTIVE: To investigate changes in rat spatial memory and hippocampal CA1 neuronal kinase system following isoflurane anesthesia, and to explore the correlation between molecular changes in cerebral neurons and behavioral manifestations following anesthesia. DESIGN, TIME AND SETTING: A randomized, controlled, animal study. All experiments were performed at the Department of Anesthesia, Beijing Chaoyang Hospital, Capital Medical University from November 2007 to December 2008. MATERIALS: A total of 72 male, 3 month-old (young group), Sprague Dawley rats, and 36 male, 20 month-old (aged group), Sprague-Dawley rats were used in the study. Isoflurane was purchased from Baxter, USA. METHODS: Young and aged rats were randomly assigned to control, training (no anesthesia, Morris water maze training), and isoflurane (1.2% isoflurane, Morris water maze training) groups. The isoflurane group was further subdivided into four groups, which were exposed to anesthesia for 2 or 4 hours, and were subjected to Morris water maze training at 2 days or 2 weeks post- anesthesia. Finally, each aged group comprised 6 rats, and the young group comprised 12 rats. MAIN OUTCOME MEASURES: Spatial learning and memory were observed during Morris water maze training. Hippocampal CA1 PKA and PKC expression and activity were detected by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). RESULTS: A 4-hour isoflurane exposure induced spatial memory deficits in all rats for 2 days to 2 weeks. In particular, aged rats exhibited more severe spatial memory deficits. Immunohistochemistry and ELISA results showed a significant increase in PKC and PKA expression and activity in the hippocampus CA1 subfield following Morris water maze training (P < 0.05). Moreover, isoflurane anesthesia inhibited PKC and PKA expression and activity, and this inhibition increased with increasing exposure duration and increasing age. CONCLUSION: Results suggested that increased isoflurane exposure and age could extensively inhibit the hippocampal CA1 kinase system. Inhibition of protein kinases could play an important role in the cognitive decline following anesthesia.

Influence of Isoflurane Exposure for 15 Consecutive Days on Ovarian Function in Adult Female Mice

Female infertility after occupational exposure to inhaled anesthetic agents has attracted critical attention,but systematic studies focusing on the impact of inhaled anesthetics on the female reproductive system have not been well-established.We used a murine model to study the effect of isoflurane exposure on infertility in female adult mice and investigated the potential underlying mechanism.One hundred adult female C57 mice were randomly allocated into 5 groups exposed in air containing 0,2500,5000,10000 or 20000 ppm isoflurane for 15 consecutive days.Estrous cycle length was measured based on vaginal smear examination,ovarian histopathologic enumeration of follicles,and serum estradiol(E2),anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)levels to assess the effect of isoflurane on ovarian reserve.Compared to the control group,significant prolongation of the estrous cycle of the adult female mice was observed in the 20000 ppm isoflurane exposure group.Serum AMH was significantly decreased,and FSH and LH levels profoundly increased in the 5000,10000,and 20000 ppm isoflurane exposure groups compared to the control group.The histopathologic examination revealed a reduced number of developing follicles and an increased number of atretic follicles after isoflurane exposure,but the difference was not statistically significant.Thus,exposure to a higher concentration of isoflurane might have an adverse effect on ovarian reserve in sexually-mature female mice.

Evaluating the Efficacy of Remifentanil-Propofol versus Isoflurane in Reducing Blood Loss with Considering Depth of Anesthesia during Endoscopic Sinus Surgery

Several methods have been suggested to decrease bleeding during surgery, one of which is the usage of hypotensive anesthetic agents. Endoscopic Sinus Surgery (ESS) is one of the surgeries which need a clear field and the amount of bleeding profoundly impacts the ability of surgeons. Current study was designed to evaluate the effect of remifentanil combined with propofol versus Isoflurane on blood loss during ESS and its possible interaction with Depth of Anesthesia. Fifty one patients comprising 15 females and 36 males undergoing ESS were chosen for this study. One group received propofol and remifentanil to induce and maintain anesthesia and the second group received Isoflurane. Mean Arterial Blood Pressure (MAP), Depth of Anesthesia and total blood loss were recorded for the patients of both group. Data were analyzed using t-test, Repeated Measures ANOVA and Pearson’s correlation. P 0.05 was considered statistically significant. Both agents induced hypotension during surgery. No significant difference was observed in total blood loss between two groups. DA was decreased in both groups, but no significant correlation was found between DA and MAP or DA and blood loss. There is no significant difference between remifentanil combined with propofol and Isoflurane in decreasing blood loss during ESS, thus we suggest usage of hypotensive anesthetic agent regardless of its type is ESS.

Comparison of Entropy vs. Bispectral Index Anesthetic Depth Monitoring during Isoflurane Anesthesia in Living Donor Liver Transplantation: Observational Study

Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.

Effect of isoflurane on expression of NR4A1 in hypoxic pulmonary artery

Objective: To investigate the effects of emulsified isoflurane on hypoxic pulmonary artery endothelial cells (HPAECs) injury and orphan nuclear receptor subfamily 4A1 (NR4A1) expression. Methods: HPAECs were divided into normal control group, model group and test group. Normal control group was cultured under normoxia. Cells in model group and test group were treated in a hypoxic chamber with oxygen concentration of about 3% (95% N2+ 5% CO2) for 2 h. The final concentration of 1 mmol·L-1 emulsified isoflurane was added to the test group, and 30% Intralipid? was added to the normal control group and the model group. MTT method was used to detect cell proliferation, Hoechst 33258 nuclear staining was used to detect cell apoptosis, Griess method was used to detect the production of NO in cell supernatant, and real-time fluorescence quantitative PCR (q-RT-PCR) was used to detect the expression of NR4A1 in cells. Results: After 12 h of intervention, the cell viability of normal control group, model group and test group were (98.45±2.41)%, (15.46±2.69)%, (79.52±4.16)%, the apoptosis rate were (2.51±0.36)%, (50.12±3.36)%, (22.15±3.42)%respectively, the concentration of NO in the culture supernatant were (59.52±4.1) μmol·L^-1, (25.16±4.85) μmol·L^-1, (43.58±6.19) μmol·L^-1, and the relative expression of NR4A1 were 1.00±0.09, 5.89±0.41, 2.39±0.24, respectively. The difference was statistically significant (P<0.05). Conclusion: Emulsified isoflurane can promote the proliferation, inhibit apoptosis and increase NO production of hypoxic HPAECs. NR4A1 may be involved in the endogenous protective mechanism of endothelial cell injury after hypoxia.

The Effects of Dexmedetomidine Continuous Rate Infusion (CRI) on Isoflurane Anaesthesia in Healthy Horses

The concept of the modern anaesthesiological technique partial intravenous anaesthesia (PIVA) is by means of infusion of different pharmacological agents as a supplement to inhalation anaesthetics to reduce the concentration of volatile agents maintaining surgical anaesthesia and to decrease their noxious side effects mainly on cardiovascular and respiratory systems. Alpha-2 agonists are agents with frequent use in equine practice either as sedatives or in general anaesthesia PIVA protocols. The most selective amongst them, dexmedetomidine, is characterized by fewer side effects, lower doses, and fast elimination which make it appropriate for application as a continuous rate infusion (CRI). The purpose of this study was to trace out the effects of dexmedetomidine continuous rate infusion (CRI) as part of PIVA using isoflurane on volatile agent requirements, cardiovascular function, respiration and coagulation parameters, and recovery in healthy horses. Six healthy horses with average age 9.0 ± 5.1 year and mean body weight 247.7 ± 71.4 kg were subjected to either 3-hour lasting isoflurane or isoflurane-dexmedetomidine anaesthesia two weeks apart. The main clinical and anaesthesiological parameters were monitored in 10 minutes intervals. Electrolytes, acid-base, blood gases, and coagulation parameters were measured at the beginning and at the end of each anaesthesia. Recovery times and qualities were also recorded. The results showed that, the addition of dexmedetomidine by CRI at 1.75 μg·kg-1·hour-1 to isoflurane anaesthesia slightly reduced isoflurane requirement for maintenance of surgical anaesthesia but had negligible effects on the recovery time and quality. PIVA using dexmedetomidine and isoflurane produced respiratory acidosis similar to isoflurane anaesthesia alone but with significantly more pronounced hypoxaemia and hyperlactaemia. Both investigated anaesthesia protocols did not influence significantly haemocoagulation parameters.

异氟烷(Isoflurane)新的吸入麻醉药

吸入麻醉药异氟烷,1965年由Terrell发现。1965年以后,在动物实验和人类的临床上被广泛使用。1976年因Corbett指出有致癌的可疑,使制造此药一时被中断。1978年EGARⅡ否认其有致癌的可能性,因而美国从1981年作为人的吸入麻醉药又在市场销售。直至最近作为兽药也开始出售。英国不久也作为人的吸入麻醉药在市场销售。

Lateral Hypothalamic Area Glutamatergic Neurons and Their Projections to the Lateral Habenula Modulate the Anesthetic Potency of Isoflurane in Mice

The lateral hypothalamic area(LHA)plays a pivotal role in regulating consciousness transition,in which orexinergic neurons,GABAergic neurons,and melanin-concentrating hormone neurons are involved.Glutamatergic neurons have a large population in the LHA,but their anesthesia-related effect has not been explored.Here,we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice.In contrast,chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery.Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram(EEG)and shifted EEG features to an arousal pattern.Photostimulation of LHA glutamatergic projections to the lateral habenula(LHb)also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level.Collectively,LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.

Protective effects of emulsified isoflurane after myocardial ischemia-reperfusion injury and its mechanism in rabbits

Objective: To evaluate the protective effects of 8% emulsified isoflurane after myocardial ischemia-reperfusion injury and its mechanism in rabbits.Methods: Twenty-four male adult New Zealand white rabbits were anesthetized with intravenous injection of 30 mg/kg pentobarbital followed by 5 mg·kg-1·h-1 infusion. All rabbits were subjected to 30 minutes of left anterior de-scending coronary artery (LAD) occlusion and 3 hours of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into three groups for precondi-tioning treatment (eight for each group). The control group (C group) received intravenously 0.9% NaCl for 30 minutes. The emulsified isoflurane group (EI group) received 8% emulsified isoflurane intravenously till 0.64% end-tidal con-centration for 30 minutes that was followed by a 15-minute washout period. The Intralipid group (IN group) received 30% Intralipid for 30 minutes. The infarcted area, plasma malondialdehyde (MDA) content, superoxide dismutase activity (SOD) and nitrite concentration after 3-hour myo-cardial perfusion were recorded simultaneously.Results: For the myocardial ischemia-reperfusion in-jury animals, the infarcted size in the EI group was signifi-cantly reduced (91.9%±8%) as compared with control group (39%±6%,t=5.19, P<0.01). The plasma SOD activity and nitrite concentration in EI group were significantly higher than those in control group (t=2.82, t=8.46, P<0.05), but MDA content was lower in EI group than that in control group (t=2.56, P<0.05).Conclusions: The results indicate that emulsified isoflurane has a cardioprotection effect against ischemia-reperfusion injury. This beneficial effect of emulsified isoflurane is probably through NO release and consequently by increase in autioxidation of myocardium.

Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein,effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters’ interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol,atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice

General anesthesia severely affects the metabolites in the brain.Glycogen,principally stored in astrocytes and providing the short-term delivery of substrates to neurons,has been implicated as an affected molecule.However,whether glycogen plays a pivotal role in modulating anesthesia-arousal remains unclear.Here,we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions.Glycogen synthase(GS)and glycogen phosphorylase(GP),key enzymes of glycogen metabolism,showed increased activity after isoflurane exposure.Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-Darabinitol(DAB),a GP antagonist,we found a prolonged time of emergence from anesthesia and an enhancedδfrequency in the EEG(electroencephalogram).In addition,augmented expression of glycogenolysis genes in glycogen phosphorylase,brain(Pygb)knock-in(PygbH11/H11)mice resulted in delayed induction of anesthesia,a shortened emergence time,and a lower ratio of EEG-δ.Our findings revealed a role of brain glycogen in regulating anesthesiaarousal,providing a potential target for modulating anesthesia.

Selective breeding of mice strains with different sensitivity to isoflurane

背景不稳定的麻药的行动的机制 unknown.Recently 是静止的，调查麻药行动的一个工具在 scale.However 增加了的遗传的使用，仅仅有限的向前基因的途径研究在哺乳动物被执行，特别与是的不稳定的麻药选择 agent.In 现在的学习，一个选择繁殖过程被设计与不同敏感生产老鼠的紧张到 isoflurane.Methods 160 男、女的处女 outbred