OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

Anesthetics, Inhalation ; pharmacology ; Child ; Electrocardiography ; Heart Rate ; drug effects ; Humans ; Isoflurane ; analogs & derivatives ; pharmacology ; Methyl Ethers ; pharmacology

BACKGROUNDIt is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp1).

METHODSA Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows: CON group, ischemia reperfusion (I/R) group, SP group , SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor II group, SP+dimethylsufoxide group, and Pim-1 inhibitor II group (n = 12, each). Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial I/R injury. The expressions of Pim-1, B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria, the Drp1 in mitochondria, and the total Drp1 and p-Drp1ser637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016.

RESULTSSP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P< 0.05). However, Pim-1 inhibitor II significantly (P < 0.05) abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P < 0.05) were upregulated. Meanwhile, SP inhibited Drp1 compartmentalization to the mitochondria followed by a reduction in the release of Cyt C. Pretreatment with Pim-1 inhibitor II significantly (P < 0.05) abolished SP-induced Pim-1/p-Drp1ser637 signaling activation.

CONCLUSIONSThese findings suggested that SP could attenuate myocardial ischemia-reperfusion injury by increasing the expression of the Pim-1 kinase. Upregulation of Pim-1 might phosphorylate Drp1 and prevent extensive mitochondrial fission through Drp1 cytosolic sequestration.

Animals ; Dynamins ; metabolism ; Hemodynamics ; drug effects ; Ischemic Postconditioning ; methods ; Male ; Methyl Ethers ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-pim-1 ; antagonists & inhibitors ; metabolism ; Quinazolinones ; pharmacology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDSevoflurane and propofol are widely used anesthetics for surgery. Studies on the mechanisms of general anesthesia have focused on changes in protein expression properties and membrane lipid. MicroRNAs (miRNAs) regulate neural function by altering protein expression. We hypothesize that sevoflurane and propofol affect miRNA expression profiles in the brain, expect to understand the mechanism of anesthetic agents.

METHODSRats were randomly assigned to a 2% sevoflurane group, 600 μg·kg - 1·min - 1 propofol group, and a control group without anesthesia (n = 4, respectively). Treatment group was under anesthesia for 6 h, and all rats breathed spontaneously with continuous monitoring of respiration and blood gases. Changes in rat cortex miRNA expression profiles were analyzed by miRNA microarrays and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Differential expression of miRNA using qRT-PCR among the control, sevoflurane, and propofol groups were compared using one-way analysis of variance (ANOVA).

RESULTSOf 677 preloaded rat miRNAs, the microarray detected the expression of 277 miRNAs in rat cortex (40.9%), of which 9 were regulated by propofol and (or) sevoflurane. Expression levels of three miRNAs (rno-miR-339-3p, rno-miR-448, rno-miR-466b-1FNx01) were significantly increased following sevoflurane and six (rno-miR-339-3p, rno-miR-347, rno-miR-378FNx01, rno-miR-412FNx01, rno-miR-702-3p, and rno-miR-7a-2FNx01) following propofol. Three miRNAs (rno-miR-466b-1FNx01, rno-miR-3584-5p and rno-miR-702-3p) were differentially expressed by the two anesthetic treatment groups.

CONCLUSIONSSevoflurane and propofol anesthesia induced distinct changes in brain miRNA expression patterns, suggesting differential regulation of protein expression. Determining the targets of these differentially expressed miRNAs may help reveal both the common and agent-specific actions of anesthetics on neurological and physiological function.

Anesthesia, General ; Animals ; Brain ; drug effects ; metabolism ; Male ; Methyl Ethers ; pharmacology ; MicroRNAs ; genetics ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

PURPOSE: The aim of this study was to evaluate the effects of premedication with oral atenolol or enalapril, in combination with remifentanil under sevoflurane anesthesia, on intraoperative blood loss by achieving adequate deliberate hypotension (DH) during orthognathic surgery. Furthermore, we investigated the impact thereof on the amount of nitroglycerin (NTG) administered as an adjuvant agent. MATERIALS AND METHODS: Seventy-three patients undergoing orthognathic surgery were randomly allocated into one of three groups: an angiotensin converting enzyme inhibitor group (Group A, n=24) with enalapril 10 mg, a beta blocker group (Group B, n=24) with atenolol 25 mg, or a control group (Group C, n=25) with placebo. All patients were premedicated orally 1 h before the induction of anesthesia. NTG was the only adjuvant agent used to achieve DH when mean arterial blood pressure (MAP) was not controlled, despite the administration of the maximum remifentanil dose (0.3 microg kg-1min-1) with sevoflurane. RESULTS: Seventy-two patients completed the study. Blood loss was significantly reduced in Group A, compared to Group C (adjusted p=0.045). Over the target range of MAP percentage during DH was significantly higher in Group C than in Groups A and B (adjusted p-values=0.007 and 0.006, respectively). The total amount of NTG administered was significantly less in Group A than Group C (adjusted p=0.015). CONCLUSION: Premedication with enalapril (10 mg) combined with remifentanil under sevoflurane anesthesia attenuated blood loss and achieved satisfactory DH during orthognathic surgery. Furthermore, the amount of NTG was reduced during the surgery.
Administration, Oral ; Adrenergic beta-Antagonists/administration & dosage/*pharmacology ; Adult ; Aged ; *Anesthesia, Inhalation ; Atenolol/administration & dosage/*pharmacology ; Blood Loss, Surgical ; Blood Pressure/drug effects ; Cardiac Output/drug effects ; Double-Blind Method ; Enalapril/administration & dosage/*pharmacology ; Female ; Heart Rate/drug effects ; Humans ; Intraoperative Care ; Male ; Methyl Ethers/*administration & dosage ; Middle Aged ; *Orthognathic Surgical Procedures ; Piperidines/*administration & dosage ; *Premedication ; Treatment Outcome

OBJECTIVETo observe the effects of preconditioning with different concentrations of sevoflurane on cariomyocyte apoptosis and myocardial inflammation in rats with sepsis and explore the possible mechanism of sevoflurane for myocardial protection.

METHODSForty adult male Sprague-Dawley rats were randomly divided into 4 groups (n=10), namely the control group, LPS group, low-concentration sevoflurane group and high-concentration sevoflurane group. Following sevoflurane pretreatment for 30 min and a washout period for 10 min, all the rats received intraperitoneal injection of LPS or normal saline (NS) and were sacrificed 12 h later to observe the myocardial histopathology. Apoptosis of the ardiomyocytes was detected with TUNEL assay, and enzyme-linked immunosorbent assay was used to detect serum cTnI level and myocardial TNF-α level.

RESULTSCompared with the control group, the rats in the other 3 groups showed significantly increased serum cTnI level, myocardial TNF-α content, and apoptotic index of the cardiomyocytes (P<0.05). Compared with those in LPS group, serum cTnI level, myocardial TNF-α content, and apoptotic index of the cardiomyocytes were significantly decreased in the two sevoflurane preconditioning groups (P<0.05), and the effect was more obvious with a high dose of sevoflurane (P<0.05 CONCLUSION: Sevoflurane preconditioning can concentration-dependently reduce LPS-induced myocardial injury in rats possibly by decreasing cardiomyocyte apoptosis and alleviating myocardial inflammations.

Animals ; Apoptosis ; Male ; Methyl Ethers ; pharmacology ; Myocarditis ; drug therapy ; Myocardium ; pathology ; Myocytes, Cardiac ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sepsis ; Troponin I ; blood ; Tumor Necrosis Factor-alpha ; metabolism

PURPOSE: Mentally disabled patients show different recovery profiles compared to normal patients after general anesthesia. However, the relationship of dose-recovery profiles of mentally disabled patients has never been compared to that of normal patients. MATERIALS AND METHODS: Twenty patients (10 mentally disabled patients and 10 mentally intact patients) scheduled to dental surgery under general anesthesia was recruited. Sevoflurane was administered to maintain anesthesia during dental treatment. At the end of the surgery, sevoflurane was discontinued. End-tidal sevoflurane and recovery of consciousness (ROC) were recorded after sevoflurane discontinuation. The pharmacodynamic relation between the probability of ROC and end-tidal sevoflurane concentration was analyzed using NONMEM software (version VII). RESULTS: End-tidal sevoflurane concentration associated with 50% probability of ROC (C50) and gamma value were lower in the mentally disabled patients (C50=0.37 vol %, gamma=16.5 in mentally intact patients, C50=0.19 vol %, gamma=4.58 in mentally disabled patients). Mentality was a significant covariate of C50 for ROC and gamma value to pharmacodynamic model. CONCLUSION: A sigmoid Emanx model explains the pharmacodynamic relationship between end-tidal sevoflurane concentration and ROC. Mentally disabled patients may recover slower from anesthesia at lower sevoflurane concentration at ROC an compared to normal patients.
*Anesthesia Recovery Period ; Anesthesia, Dental/*methods ; Anesthesia, General/*methods ; Anesthetics, Inhalation/*administration & dosage/pharmacology ; Case-Control Studies ; Child ; Child, Preschool ; Consciousness/drug effects ; Dental Care for Disabled/*methods ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Mentally Disabled Persons ; Methyl Ethers/*administration & dosage/pharmacology

OBJECTIVETo investigate the effects of sevoflurane on cytosolic phospholipase A₂ (C-PLA₂) and clara cell secretory protein (CCSP) in lung tissues of rabbits with one-lung ventilation (OLV)-induced lung injuries.

METHODSThirty-six healthy Japanese white rabbits were randomized into sham-operated group, OLV group, and OLV plus sevoflurane group subdivided into 4 subgroups with sevoflurane concentrations of 1%, 2%, 3% and 4%. CCSP and C-PLA₂ mRNA and protein expressions in rabbit lung tissues were detected by Western blotting and real-time PCR, and the content of arachidonic acid (AA) was measured using ELISA. The severities of the lung injury were evaluated according to lung wet/dry weight (W/D) ratio and histological scores.

RESULTSIn the OLV group and OLV+ sevoflurane groups, pulmonary CCSP expressions were significantly lower, while C-PLA₂ expression, lung W/D ratios and lung histological scores were significantly higher than those in the sham-operated group (P<0.05). Compared with OLV group, the OLV+sevoflurane groups showed significantly increased expressions of CCSP and reduced C-PLA₂ expression, lung W/D ratios and histological scores (P<0.05). In the 4 OLV+sevoflurane groups, CCSP expressions underwent no significant changes as sevoflurane concentration increased, but C-PLA₂ expressions, lung W/D ratios and histological scores all decreased gradually as the concentrations of sevoflurane increased (P<0.05).

CONCLUSIONOLV can result in down-regulated CCSP expressions and up-regulated C-PLA₂ expressions in rabbit lung tissues. Sevoflurane can protect against OLV-induced acute lung injury possibly by inhibiting C-PLA₂ expression via up-regulation of CCSP expressions or through other mechanisms resulting in down-regulated expression of C-PLA₂.

Animals ; Female ; Lung ; metabolism ; pathology ; Male ; Methyl Ethers ; pharmacology ; One-Lung Ventilation ; adverse effects ; Phospholipases A2 ; metabolism ; Rabbits ; Uteroglobin ; metabolism ; Ventilator-Induced Lung Injury ; metabolism

BACKGROUND: The aims of this study were to compare the stability, correlation with end-tidal sevoflurane, and area below the effect (AUCeffect) vs. time curves of temporal linear mode complexity (TLMC) and approximate entropy (ApEn) during sevoflurane anesthesia. Another study goal was to characterize the time course of the effects of sevoflurane. METHODS: Electroencephalogram (EEG) parame1ter stability was evaluated using the coefficients of variation (CV) of the median baseline (E0), maximal (Emax), and individual median E0 - Emax values. Correlations between sevoflurane concentration and EEG parameters were tested. AUCeffect vs. time curves of TLMC and ApEn were calculated to quantitate any decrease in central nervous system activities. A sigmoid Emax model was used for pharmacodynamic modeling. RESULTS: TLMC and ApEn demonstrated CVs of 8.36 and 7.35 (for E0) and 19.61 and 13.45 (Emax), respectively. The CVs of the individual median E0 - Emax values were 65.16 for TLMC and 59.97 for ApEn. The Spearman correlation coefficient was -0.3103 for TLMC and -0.3410 for ApEn (P < 0.001 for both parameters). The median AUCeffect value was 338.9 for TLMC and 246.5 for ApEn (P = 0.457). The final pharmacodynamic parameters estimated by sigmoid Emax models were described as follows; E0: 0.614, 0.617, Emax: 0.334, 0.287, Ce50: 5.48, 5.07 vol%, gamma: 1.88, 2.01, ke0: 0.306, 0.236 min (TLMC, ApEn). CONCLUSIONS: TLMC is comparable to ApEn according to the univariate EEG descriptors of the effects of sevoflurane. A sigmoid Emax model well described the pharmacodynamics of sevoflurane for TLMC and ApEn.
Anesthesia* ; Central Nervous System ; Colon, Sigmoid ; Electroencephalography ; Entropy ; Methyl Ethers ; Pharmacology ; Subject Headings

OBJECTIVETo explore the effect of simulated navigation stimulation on the anesthetic sensitivity of sevoflurane in rats, so as to provide basis for rational using sevoflurane during navigation.

METHODSSD rats were stimulated by Crampton model and the conditioned taste aversion (CTA) was regarded as criterion of motion sickness. (1) 60 rats were randomly divided into control (n = 15) and rotation group (n = 45). The changes of behavior and autonomic activity, sevoflurane concentration achieved sleep and anesthesia states, and the revitalization time were observed in two group rats. (2) 32 rats were randomly divided into control (I), rotation (II), anesthesia (III) and rotation plus anesthesia (IV) group (n = 8). The acetylcholine (Ach), norepinephrine (NE), r-aminobutyric acid (GABA), glutamic acid (Glu) of brain cortex, thalamus and hippocampus were determined respectively in the four group rats.

RESULTSIn control group, the sevoflurane concentration achieved sleep and anesthesia states were 1.74% +/- 0.05% and 3.54% +/- 0.05% respectively, but, those concentrations were 1.51% +/- 0.06% and 3.14% +/- 0.08% in rotation group. There were lower significantly in rotation group than those in control group (P < 0.01). It was a major characteristic that all of the neurotransmitters were reduced significantly in II group, this was even more in brain cortex and thalamus (P < 0.01). In II group, Ach was upward in brain cortex, NE and GABA were reduced in hippocampus obviously. The change tendency of neurotransmitters in IV group was more close to II group, that was, the effect of rotation stimulation was more obvious.

CONCLUSIONThe anesthetic sensitivity of sevoflurane could be obvious increased in rats simulated navigation stimulation.

Anesthetics ; pharmacology ; Animals ; Cerebral Cortex ; drug effects ; metabolism ; Gravity, Altered ; Hippocampus ; drug effects ; metabolism ; Male ; Methyl Ethers ; pharmacology ; Neurotransmitter Agents ; analysis ; Norepinephrine ; analysis ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Rotation ; Thalamus ; drug effects ; metabolism ; gamma-Aminobutyric Acid ; analysis