Reducing the environmental impact of mask inductions in children: A quality improvement report.

BACKGROUND: Inhalational anesthetic agents are potent greenhouse gases with global warming potential that far exceed that of carbon dioxide. Traditionally, pediatric inhalation inductions are achieved with a volatile anesthetic delivered to the patient in oxygen and nitrous oxide at high fresh gas flows. While contemporary volatile anesthetics and anesthesia machines allow for a more environmentally conscious induction, practice has not changed. We aimed to reduce the environmental impact of our inhalation inductions by decreasing the use of nitrous oxide and fresh gas flows. METHODS: Through a series of four plan-do-study-act cycles, the improvement team used content experts to demonstrate the environmental impact of the current inductions and to provide practical ways to reduce this, by focusing on nitrous oxide use and fresh gas flows, with visual reminders introduced at point of delivery. The primary measures were the percentage of inhalation inductions that used nitrous oxide and the maximum fresh gas flows/kg during the induction period. Statistical process control charts were used to measure improvement over time. RESULTS: 33 285 inhalation inductions were included over a 20-month period. nitrous oxide use decreased from 80% to <20% and maximum fresh gas flows/kg decreased from a rate of 0.53 L/min/kg to 0.38 L/min/kg, an overall reduction of 28%. Reduction in fresh gas flows was greatest in the lightest weight groups. Induction times and behaviors remained unchanged over the duration of this project. CONCLUSIONS: Our quality improvement group decreased the environmental impact of inhalation inductions and created cultural change within our department to sustain change and foster the pursuit of future environmental efforts.

Retrospective Comparison between the Effects of Propofol and Inhalation Anesthetics on Postoperative Recurrence of Early- and Intermediate-Stage Hepatocellular Carcinoma.

OBJECTIVE: Previous studies have reported that propofol has antitumor, anti-inflammatory, and antioxidant effects in addition to its anesthetic properties. To confirm this, a retrospective investigation was conducted to determine whether different anesthetic agents, particularly propofol and inhalation anesthetics, have an effect on the recurrence of hepatocellular carcinoma (HCC) in patients who were diagnosed with primary HCC and underwent laparoscopic hepatectomy. SUBJECTS AND METHODS: Patients with Barcelona Clinic Liver Cancer stages 0, A, and B HCC, who underwent laparoscopic hepatic resection, were enrolled in this study. Post-operative HCC recurrence, which was determined from postoperative liver CT, was evaluated 24 months postoperatively with respect to the main anesthetic agents. The characteristics of HCC and other patient-related or surgery-related variables were evaluated together. RESULTS AND CONCLUSION: During the 24-month period after hepatic resection, less HCC patients in the propofol group than in the inhalation group recurred (p = 0.046). The mean time to recurrence was 20.8 months (95% CI, 19.7-22.0) and 19.1 months (95% CI, 17.8-20.4) in the propofol group and the inhalation group, respectively. In addition, multivariable Cox proportional regression analysis revealed that the propofol group showed significantly decreased recurrence versus the inhalation group (hazard ratio, 0.57; 95% CI, 0.47-0.69; p = 0.029). When propofol was used as the main general anesthetic agent for laparoscopic hepatic resection, the postoperative 2-year recurrence rate decreased in early- and intermediate-stage HCC.

Beclin1-mediated ferroptosis activation is associated with isoflurane-induced toxicity in SH-SY5Y neuroblastoma cells.

The widely used inhalation anesthetic, isoflurane, potentially induces neuronal injury in clinical practice. Previous studies showed multiple forms of cell death that resulted from isoflurane-induced cytotoxicity, but the precise underlying mechanism remains poorly understood. Ferroptosis has recently been identified as a non-apoptotic form of regulated cell death. Here, we found that ferroptosis inhibitors, ferrostatin-1 and deferoxamine mesylate (DFOM), showed great efficiency in maintaining cell viability in SH-SY5Y neuroblastoma cells exposed to a high concentration of isoflurane for 24 h. We also observed that cellular chelatable iron and lipid peroxidation were increased in a concentration-dependent manner in response to isoflurane. In addition, isoflurane upregulated Beclin1 phosphorylation, followed by the formation of a Beclin1-solute carrier family 7 member 11 (SLC7A11) complex, which affected the activity of cystine/glutamate antipoter and further regulated ferroptotic cell death. Accordingly, Beclin1 overexpression aggravated isoflurane-induced cell damage by upregulating ferroptosis. This phenomenon was significantly attenuated by silencing of Beclin1 in SH-SY5Y cells. These findings indicate that Beclin1 may regulate ferroptosis in a manner involving inhibition of glutamate exchange activity of system xc(-), which is implicated in isoflurane-induced toxicity. In particular, when isoflurane is administrated at high concentrations and for an extended duration, ferroptosis is more likely to play a crucial role in isoflurane-induced toxicity.

Fetal Surgery Decreases Anesthesia-Induced Neuroapoptosis in the Mid-Gestational Fetal Ovine Brain.

BACKGROUND: Studies demonstrating an association between anesthesia and brain cell death (neuroapoptosis) in young animals were performed without accompanying surgery. This study tests the hypothesis that fetal surgery decreases anesthesia-induced neuroapoptosis. MATERIALS AND METHODS: Seventy-day-pregnant ewes received 2% isoflurane for 1 h (low dose [LD]) or 4% for 3 h (high dose [HD]) with or without fetal surgery (S). Unexposed fetuses served as controls (C). Fetal brains were processed for neuroapoptosis using anti-caspase-3 antibodies. Data were analyzed using ANOVA. RESULTS: Twenty-eight fetal sheep were evaluated. Dentate gyrus neuroapoptosis was lower in the HD+S group (13.1 ± 3.76 × 105/mm3) than in the HD (19.1 ± 1.40 × 105/mm3, p = 0.012) and C groups (18.3 ± 3.55 × 105/mm3, p = 0.035). In the pyramidal layer of the hippocampus, neuroapoptosis was lower in the HD+S group (8.11 ± 4.88 × 105/mm3) than in the HD (14.8 ± 2.82 × 105/mm3, p = 0.006) and C groups (14.1 ± 4.54 × 105/mm3, p = 0.019). The LD+S group showed a trend towards a significant decrease in neuroapoptosis in the pyramidal layer (LD+S 7.51 ± 1.48 vs. LD 13.5 ± 1.87 vs. C 14.1 ± 4.54 × 105/mm3, p = 0.07) but not in the dentate gyrus. Fetal surgery did not affect neuroapoptosis in the frontal cortex or endplate. CONCLUSIONS: Fetal surgery decreases isoflurane-induced neuroapoptosis in the dentate gyrus and the pyramidal layer of mid-gestational fetal sheep. Long-term effects of these observations on memory and learning deserve further exploration.

The negative effects of chronic exposure to isoflurane on spermatogenesis via breaking the hypothalamus-pituitary-gonadal equilibrium.

This study aims to investigate the negative effects of chronic exposure to isoflurane on spermatogenesis and explore the underlying mechanisms. Sixty male rats were randomly allocated to two groups: control group, receiving no treatment, and anesthesia group, administrated exposure to isoflurane (2 ppm) for 25 consecutive days (1 h/day). The negative effects of chronic exposure to isoflurane were evaluated by analyzing the median eminence GnRH content, the relevant hormone levels, some sperm parameters and the mRNA expressions for some reproduction-related genes. Isoflurane significantly decreased the GnRH content and the serum gonadotrophin levels compared with the control group (p<0.01). Meanwhile, the mRNA expressions of GnRH in hypothalamus, GnRH receptor, luteinizing hormone (LH)-ß and follicle-stimulating hormone (FSH)-ß in pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited (p<0.01). Furthermore, the mRNA expressions of androgen receptor (AR), kisspeptin encoded gene (Kiss-1) and its receptor (GPR54) in hypothalamus were significantly diminished by isoflurane (p<0.01). The results indicated that chronic exposure to isoflurane diminished the synthesis and secretion of GnRH by inhibiting the androgen-AR-Kisspeptin-GPR54 pathway and breaking the hypothalamic-pituitary-gonadal equilibrium, and therefore it could inhibit spermatogenesis.

Balanced volatile sedation with isoflurane in critically ill patients with aneurysmal subarachnoid hemorrhage - a retrospective observational study.

Introduction: In patients with severe aneurysmal subarachnoid hemorrhage (SAH) deep sedation is often used early in the course of the disease in order to control brain edema formation and thus intracranial hypertension. However, some patients do not reach an adequate sedation depth despite high doses of common intravenous sedatives. Balanced sedation protocols incorporating low-dose volatile isoflurane administration might improve insufficient sedation depth in these patients. Methods: We retrospectively analyzed ICU patients with severe aneurysmal SAH who received isoflurane in addition to intravenous anesthetics in order to improve insufficient sedation depth. Routinely recorded data from neuromonitoring, laboratory and hemodynamic parameters were compared before and up to 6 days after initiation of isoflurane. Results: Sedation depth measured using the bispectral index improved in thirty-six SAH patients (-15.16; p = 0.005) who received additional isoflurane for a mean period of 9.73 ± 7.56 days. Initiation of isoflurane sedation caused a decline in mean arterial pressure (-4.67 mmHg; p = 0.014) and cerebral perfusion pressure (-4.21 mmHg; p = 0.013) which had to be balanced by increased doses of vasopressors. Patients required increased minute ventilation in order to adjust for the increase in PaCO2 (+2.90 mmHg; p < 0.001). We did not detect significant increases in mean intracranial pressure. However, isoflurane therapy had to be terminated prematurely in 25% of the patients after a median of 30 h due to episodes of intracranial hypertension or refractory hypercapnia. Discussion: A balanced sedation protocol including isoflurane is feasible for SAH patients experiencing inadequately shallow sedation. However, therapy should be restricted to patients without impaired lung function, hemodynamic instability and impending intracranial hypertension.

Establishing a health-based recommended occupational exposure limit for isoflurane using experimental animal data: a systematic review protocol.

BACKGROUND: Isoflurane is used as an inhalation anesthetic in medical, paramedical, and veterinary practice. Epidemiological studies suggest an increased risk of miscarriages and malformations at birth related to maternal exposure to isoflurane and other inhalation anesthetics. However, these studies cannot be used to derive an occupational exposure level (OEL), because exposure was not determined quantitatively and other risk factors such as co-exposures to other inhalation anesthetics and other work-related factors may also have contributed to the observed adverse outcomes. The aim of this systematic review project is to assess all available evidence on the effects of isoflurane in studies of controlled exposures in laboratory animals to derive a health-based recommended OEL. METHODS: A comprehensive search strategy was developed to retrieve all animal studies addressing isoflurane exposure from PubMed, EMBASE, and Web of Science. Title-abstract screening will be performed by machine learning, and full-text screening by one reviewer. Discrepancies will be resolved by discussion. We will include primary research in healthy, sexually mature (non human) vertebrates of single exposure to isoflurane. Studies describing combined exposure and treatments with > = 1 vol% isoflurane will be excluded. Subsequently, details regarding study identification, study design, animal model, and intervention will be summarized. All relevant exposure characteristics and outcomes will be extracted. The risk of bias will be assessed by two independent reviewers using an adapted version of the SYRCLE's risk of bias tool and an addition of the OHAT tool. For all outcomes for which dose-response curves can be derived, the benchmark dose (BMD) approach will be used to establish a point of departure for deriving a recommended health-based recommended OEL for 8 h (workshift exposure) and for 15 min (short-term exposure). DISCUSSION: Included studies should be sufficiently sensitive to detect the adverse health outcomes of interest. Uncertainties in the extrapolation from animals to humans will be addressed using assessment factor. These factors are justified in accordance with current practice in chemical risk assessment. A panel of experts will be involved to reach consensus decisions regarding significant steps in this project, such as determination of the critical effects and how to extrapolate from animals to humans. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022308978.

High anesthetic (isoflurane) indoor pollution is associated with genetic instability, cytotoxicity, and proliferative alterations in professionals working in a veterinary hospital.

This is the first study to monitor anesthetic pollution in veterinary operating rooms (VOR) and assess the toxicological impact of the inhalational anesthetic isoflurane (exposed group) compared to matched volunteers (control group). DNA damage was evaluated in mononuclear cells by the comet assay while genetic instability (including micronucleus-MN), cell proliferation, and cell death markers were assessed by the buccal MN cytome assay. Residual isoflurane concentrations in VOR (air monitoring) lacking the scavenging system were assessed by infrared spectrophotometry; the mean concentration was 11 ppm (≥ 5 times above the international recommended threshold). Comet assay results did not differ between groups; however, both younger exposed professionals (with higher week workload) compared to older individuals exposed for the same period and older professionals with greater time of exposure (years) compared to those in the same age group with fewer years of exposure presented higher DNA damage. The exposed group had a higher frequency of MN, nuclear buds, binucleated cells, karyorrhexis, and karyolysis and a lower frequency of basal cells than the control group. Exposed women were more vulnerable to genetic instability and proliferative index; exposed men presented more cytotoxicity. High WAG exposure has deleterious effects on exposed professionals.

Gene and systemic inflammatory effects and neuroendocrine response in surgical patients anesthetized with desflurane-nitrous oxide or desflurane-nitrous oxide-free: A randomized trial.

There is growing interest in assessing possible immunotoxicological effects in anesthetized patients. There are controversial findings concerning the effect of nitrous oxide (N2O) anesthetic gas effect on inflammatory response. We tested the hypothesis that N2O associated with desflurane (inhalational anesthetic) was likely to worsen neuro-immune-endocrine effects when compared with desflurane alone in this randomized trial. The primary endpoint of this study was to evaluate the systemic proinflammatory interleukin (IL)-6, and the secondary endpoints included other systemic (IL-1ß, TNF-α, IL-8, IL-10, IL-17A and high-sensitivity C-reactive protein - hs-CRP) and genetic inflammatory markers (NF-kB, IL-6 and COX-2) as well as hormones (adrenocorticotropic hormone, cortisol and prolactin) comparing patients undergoing minor surgery with or without N2O-desflurane. As a second aim, we assessed whether there were changes in the neuro-immune-endocrine profiles within each group. Blood samples were collected before anesthesia, 90 min after anesthesia induction, and the day after surgery. We assessed serum cytokines using a cytometric bead array and hs-CRP by chemiluminescent immunoassay. Expression of three proinflammatory transcripts was assessed by real-time quantitative polymerase chain reaction, and neuroendocrine hormones were detected by chemiluminescent microparticle immunoenzymatic assay. There were no significant between-group differences for any analyzed biomarkers. However, there was a significant increase in: (a) systemic IL-6 and hs-CRP values one day after surgery in both groups and (b) prolactin levels in the intraoperative period compared to baseline and postoperative period levels for both groups. In conclusion, N2O does not impair the inflammatory profile and neuroendocrine response compared to patients who receive only desflurane anesthesia.

Inflammation and DNA damage induction in surgical patients maintained with desflurane anesthesia.

The use of anesthetics during surgical interventions may contribute to disorders in the perioperative period. Desflurane is the newest volatile halogenated anesthetic to be introduced in clinical practice. Considering that inflammation and genotoxicity are linked events, and that little is known regarding possible genetic and inflammatory effects of desflurane in surgical patients, this study evaluated DNA damage, systemic inflammatory cytokines and related gene expression in adult patients without comorbidities who underwent minor otorhinological surgeries under general anesthesia maintained with the inhalational anesthetic desflurane. This study involved a self-controlled design in which venous blood samples were collected from subjects before anesthesia administration and after the surgical procedure. The comet assay was applied to assess DNA lesions, while the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were evaluated by flow cytometry. A genotoxic effect was observed (p = 0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (p = 0.001 and p = 0.02, respectively), whereas the levels of the other cytokines did not significantly change. Considering that serum IL-6 and IL-8 were increased, we further evaluated IL-6 and IL-8 gene expression by quantitative real-time polymerase chain reaction (qPCR). However, IL-6 and IL-8 gene expression was unaltered (p >  0.05). In conclusion, anesthetic maintenance with the modern agent desflurane during minor surgeries led to genotoxic and inflammatory effects without altering the expression of inflammation related-genes the day after surgery in patients without comorbidities.

Early, Subclinical Hematological Changes Associated with Occupational Exposure to High Levels of Nitrous Oxide.

This study was undertaken to determine whether exposure of operating room personnel to inhalation anesthetics, nitrous oxide, isoflurane, and sevoflurane was associated with any hematological changes. This historical cohort study was performed in 2018 at a large public hospital in Shiraz, where 52 operating room personnel and 52 administrative staff were investigated. The blood sample was taken from all individuals for Complete Blood Count. Furthermore, demographic information was collected through questionnaires. Mean atmospheric concentrations of nitrous oxide, isoflurane, and sevoflurane, to which subjects were exposed, were 850.92, 2.40, and 0.18 ppm, respectively. The hematological parameters were within the normal range in both groups. However, the mean values of hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count in the exposed group were significantly lower than the control group. No significant differences were noted between the two groups as far as other hematological factors were concerned. These findings provide circumstantial evidence to further substantiate the notion that occupational exposure to inhalation anesthetics, under the exposure scenario explained in this study, is associated with subtle, subclinical, prepathologic hematological changes. Long-term consequence and ramifications of these effects require further investigation. The range of exposure levels to anesthetic gases in operating rooms.

Monitoring early cell damage in physicians who are occupationally exposed to inhalational anesthetics.

Worldwide, millions of professionals who work in operating rooms are occupationally exposed to inhalational anesthetics. Thus, the potential health effects of the continuous exposure to inhalational anesthetics on individuals in the operating room remain a subject of debate. Human biomonitoring is a potentially useful tool for assessing the health of exposed professionals. No report has yet evaluated the possible cytotoxic and genotoxic effects of the most commonly used inhalational anesthetics on young professionals who are occupationally exposed. Considering the importance of this issue, we monitored physicians who were exposed to inhalational anesthetics during their first year of a medical residency program to evaluate the possible early damage events. Twenty-six young physicians who had been occupationally exposed to the anesthetics isoflurane, sevoflurane, desflurane, and nitrous oxide and who worked in operating rooms using modern anesthesia workstations during their medical residency program, participated in this study. Blood samples were evaluated before the start of the program (before the exposure), and after 1/2 year and 1 year of exposure. We monitored the subjects by assessing the cytotoxicity (early apoptosis and loss of the mitochondrial membrane potential) using flow cytometry and genotoxicity using the comet assay. No significant changes were observed in the biomarkers of cytotoxicity or genotoxicity (p > 0.05). Thus, biomonitoring showed that short-term exposure to inhalational anesthetics did not induce early cell damage during the first year of medical residency. Based on the results, brief occupational exposure to anesthetics does not induce either cytotoxicity or genotoxicity in mononuclear cells under the conditions of this study. Thus, young physicians should undergo additional biomonitoring at the beginning of their careers to determine possible toxic effects on their cells and genetic material, and further investigations are warranted to determine whether a longer exposure to inhalational anesthetics results in mitochondrial depolarization, apoptosis and DNA breaks.

Ligand partitioning into lipid bilayer membranes under high pressure: Implication of variation in phase-transition temperatures.

The variation in phase-transition temperatures of dipalmitoylphosphatidylcholine (DPPC) bilayer membrane by adding two membrane-active ligands, a long-chain fatty acid (palmitic acid (PA)) and an inhalation anesthetic (halothane (HAL)), was investigated by light-transmittance measurements and fluorometry. By assuming the thermodynamic colligative property for the bilayer membrane at low ligand concentrations, the partitioning behavior of these ligands into the DPPC bilayer membrane was considered. It was proved from the differential partition coefficients between two phases that PA has strong affinity with the gel (lamellar gel) phase in a micro-molal concentration range and makes the bilayer membrane more ordered, while HAL has strong affinity with the liquid crystalline phase in a milli-molal concentration range and does the bilayer membrane more disordered. The transfer volumes of both ligands from the aqueous solution to each phase of the DPPC bilayer membrane showed that the preferential partitioning of the PA molecule into the gel (lamellar gel) produces about 20% decrease in transfer volume as compared with the liquid crystalline phase, whereas that of the HAL molecule into the liquid crystalline phase does about twice increase in transfer volume as compared with the gel (ripple gel) phase. Furthermore, changes in thermotropic and barotropic phase behavior of the DPPC bilayer membrane by adding the ligand was discussed from the viewpoint of the ligand partitioning. Reflecting the contrastive partitioning of PA and HAL into the pressure-induced interdigitated gel phase among the gel phases, it was revealed that PA suppresses the formation of the interdigitated gel phase under high pressure while HAL promotes it. These results clearly indicate that each phase of the DPPC bilayer membrane has a potential to recognize various ligand molecules.

Reinvestigation of the Two-step Synthesis of Sevoflurane.

Improvements in the two-step synthesis of 1,1,1,3,3,3-hexafluoro-2- (fluoromehoxy)propane (Sevoflurane) that result in the product cost reduction, safety level enhancement and positive environmental impacts are described. This process consists of chloromethylation reaction of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) followed by a halogen-exchange fluorination. This is the first synthesis of Sevoflurane in Iran which was successfully scaled up. During this work, several improvements have been achieved by optimization of the reaction time, the amount of consumed starting materials and solvents and work up procedure while keeping the yield and purity intact. The reaction time of the first step (24 h) was diminished to 4 h. (19)F NMR spectroscopy was used to investigate the rate of the reaction in the first step and to evaluate the influence of different parameters mentioned on the achieved improvements.

Case report: proximal tubule impairment following volatile anesthetic exposure.

The safety of contemporary volatile anesthetic agents with respect to kidney function is well established, and growing evidence suggests that volatile anesthetics even protect against ischemic nephropathy. However, studies examining effects of volatile anesthetics on kidney function frequently demonstrate transient proteinuria and glycosuria following exposure to these agents, although the cause of these findings has not been thoroughly examined. We describe the case of a patient who underwent a neurosurgical procedure, then experienced glycosuria without hyperglycemia that resolved within days. Following a second neurosurgical procedure, the patient again developed glycosuria, now associated with ketonuria. Further examination demonstrated nonalbuminuric proteinuria in conjunction with urinary wasting of phosphate and potassium, indicative of proximal tubule impairment. We suggest that transient proximal tubule impairment may play a role in the proteinuria and glycosuria described following volatile anesthetic exposure and discuss the relationship between these observations and the ability of these agents to protect against ischemic nephropathy.

Effects of sevoflurane and halothane anesthesia on liver circulation and oxygen metabolism in the dog during hepatolobectomy.

PURPOSE: Effects of sevoflurane and halothane anesthesia on liver circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, with the aim of choosing a better anesthetic for hepatic resection. METHODS: Sixteen mongrel dogs were randomly divided into two groups with eight in each. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows (1) before the inhalation of each anesthetic (base line); (2) 1 h after the start of inhalation of 1.5 minimum alveolar concentration (MAC) anesthetic; (3) 1 h after hepatolobectomy with the same MAC of anesthesia; and (4) 2 h after the discontinuation of anesthesia. Measurements of systemic hemodynamics, blood gas tensions, plasma enzyme leaks and arterial ketone body ratio were made at the same time. RESULTS: Sevoflurane maintained hepatic arterial blood flow better than halothane anesthesia, both before and after hepatolobectomy. Hepatic arterial vascular resistance increased in the halothane group but did not change in the sevoflurane group after hepatolobectomy. No significant difference was found in oxygen metabolism and arterial ketone body ratio between two groups. Serum enzyme leakage was less in the sevoflurane group. CONCLUSION: Sevoflurane has less adverse effects on liver circulation, especially hepatic arterial blood flow, and hepatic function than halothane in the case of hepatolobectomy.

Isoflurane Enhances the Expression of Cytochrome C by Facilitation of NMDA Receptor in Developing Rat Hippocampal Neurons In Vitro / 华中科技大学学报（医学）（英德文版）

This study examined the effects of clinically relevant concentrations of isoflurane on the amplitude of NMDA receptor current (INMDA) and the expression of cytochrome C in cultured developing rat hippocampal neurons.The hippocampi were dissected from newborn Sprague-Dawley rats.Hippocampal neurons were primarily cultured for 5 days and then treated with different concentrations of isoflurane [(0.25,0.5,0.75,1 minimum alveolar concentration (MAC))].The peak of INMDA was recorded by means of the whole cell patch clamp technique.The cytochrome C level was detected by Western blotting and quantitative real-time PCR.Our results showed that isoflurane (0.25,0.5,0.75 and 1 MAC) potentiated the amplitude of INMDA by (116±8.8)％,(122±11.7)％,(135±14.3)％ and (132±14.6)％,respectively,and isoflurane increased the mRNA expression of cytochrome C in a concentration-dependent manner.The cytochrome C mRNA expression reached a maximum after 0.5 MAC isoflurane stimulation for 6 h (P＜0.05).It was concluded that isoflurane enhances the expression of cytochrome C in cultured rat hippocampal neurons,which may be mediated by facilitation of NMDA receptor.