General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

Anesthesia,Anesthetics,and Postoperative Cognitive Dysfunction in Elderly Patients

Postoperative cognitive dysfunction(POCD)remains a major issue that worsens the prognosis of elderly surgery patients.This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients,aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols,ultimately reducing the incidence of POCD in elderly surgery patients.

Inhaled volatile anesthetics in the intensive care unit

The discovery and utilization of volatile anesthetics has significantly transformed surgical practices since their inception in the mid-19th century.Recently,a paradigm shift is observed as volatile anesthetics extend beyond traditional confines of the operating theatres,finding diverse applications in intensive care settings.In the dynamic landscape of intensive care,volatile anesthetics emerge as a promising avenue for addressing complex sedation requirements,managing refractory lung pathologies including acute respiratory distress syndrome and status asthmaticus,conditions of high sedative requirements including burns,high opioid or alcohol use and neurological conditions such as status epilepticus.Volatile anesthetics can be administered through either inhaled route via anesthetic machines/devices or through extracorporeal membrane oxygenation circuitry,providing intensivists with multiple options to tailor therapy.Furthermore,their unique pharmacokinetic profiles render them titratable and empower clinicians to individualize management with heightened accuracy,mitigating risks associated with conventional sedation modalities.Despite the amounting enthusiasm for the use of these therapies,barriers to widespread utilization include expanding equipment availability,staff familiarity and training of safe use.This article delves into the realm of applying inhaled volatile anesthetics in the intensive care unit through discussing their pharmacology,administration considerations in intensive care settings,complication considerations,and listing indications and evidence of the use of volatile anesthetics in the critically ill patient population.

Different Volumes of Local Anesthetics in Ultrasound-Guided Combined Interscalene-Supraclavicular Block for Traumatic Humeral Fracture

Background: Procedures that require anesthesia of entire length of the arm should have combined Interscalene block (ISB) and Supraclavicular block (SCB) to ensure adequate block. However, dual block requires high dose of local anesthetic (LA). We examined if Ultrasound (U/S) guided block helps to decrease the required volume of LA by visualizing trunks, so we only need injection of LA toward cervical nerve roots C5 and C6 aiming to block branches escaped from supraclavicular block. Patients and methods: Ninety-three patients were randomly allocated into one of three equal groups, each included 31 patients. All patients received SCB 20 ml (10 ml Bupivacaine 0.5% plus 10 ml lidocaine 2%) and ISB with different volumes of LA according to the group as follow: group A: 20 ml, group B: 15 ml, and group C: 10 ml. Result: No significant difference in onset of block (sensory and motor) and duration of block (motor only) between the three groups (P value > 0.05). The duration of sensory block was significantly longer in group A (760.65 ± 30.87 minutes) than in either group B (740.48 ± 21.15 minutes, P value P value P value P value P value P value < 0.001). Conclusion: A reduced volume of LA can be used in ultra sound guided ISB in combined with SCB to give satisfactory level of anesthesia to entire length of the arm, but the sensory block duration and duration of post-operative analgesia will be decreased significantly with decreasing the volume.

Comparative studies on the binding site of anesthetics to GABA a receptors using in silico docking methods

Although the GABAA receptor(GABAAR)has been proposed as the main action site for sevoflurane,isoflurane,halothane,enflurane,propofol,and benzodiazepines(BZDs),binding of these anesthetics with high-resolution structures of the GABAAR have been rarely examined by comparative docking analyses.Moreover,various combinations of ligands on more GABAARs with various subtypes need to be analyzed to understand the elaborate action mechanism of GABAARs better because some GABAA ligands showed specificity toward the distinct subtypes of the GABAAR.Methods:We performed in silico docking analysis to compare the binding modes of sevoflurane,isoflurane,halothane,enflurane,propofol,and BZDs to the GABAAR based on one of the most recently provided 3D structures.We performed the docking analysis and the affinity-based ranking of the binding sites.Results:Our docking studies revealed that isoflurane,halothane,and enflurane docked in an extracellular domain(ECD)on GABAARs,in contrast to sevoflurane.Conclusion:Our results supported a multi-site mechanism for the allosteric modulation of propofol.Propofol was bound to the pore or favored various subsites in the transmembrane domain(TMD).Our result confirmed that different chemically related BZD ligands interact via distinct binding modes rather than by using a common binding mode,as previously suggested.

Anesthetic effect of phenobarbital sodium on female BALB/c mice

Objective:Anesthetics are of great importance in avoiding severe pain and suffering in animals and ensuring experimental progress.This study was aimed at elucidating the anesthesia score of phenobarbital sodium as a general anesthetic at different concentrations and doses in BALB/c mice,and finding the suitable anesthesia strategies for experimental surgeries.Methods:Phenobarbital sodium was administrated intraperitoneally at the doses of 75,100,125,150,and 200 mg/kg and randomly in different concentrations(2%,5%,and 10%)to female BALB/c mice.The anesthesia score was evaluated based on the stimulus index including tail-pinch,front and hind limb withdrawal,and eyelid reflexes.The speed and duration of anesthesia in different groups were recorded per the occurrence and duration of the righting reflex.Results:The anesthetic effect of phenobarbital sodium on female BALB/c mice showed an obvious dose-dependency.Respiratory suppression caused by high-dose anesthesia may lead to mouse death.Based on the anesthesia score,when the phenobarbital sodium treatment was greater than or equal to five percent or 200 mg/kg,more than 80%mice meet the anesthesia depth that surgical operation needed.The rates of achieving surgical anesthesia depth(standard-reaching rate)in mice treated with 2%sodium phenobarbital were 0%in the 75 mg/kg group,0%in the 100 mg/kg group,50%in the 125 mg/kg group,66.7%in the 150 mg/kg group,and 100%in the 200 mg/kg group.The standard-reaching rate of mice treated with 5%concentration of phenobarbital sodium were:0%in the 75 mg/kg group,0%in the 100 mg/kg group,83.33%in the 125 mg/kg group,100%in the 150 mg/kg group,and 100%in the 200 mg/kg group.The standard-reaching rate of mice treated with 10%concentration of phenobarbital sodium were:50%in the 75 mg/kg group,66.7%in the 100 mg/kg group,100%in the 125 mg/kg group,100%in the 150mg/kg group,and 100%in the 200 mg/kg group.Sedation and hypnosis were induced in the low-concentration dose group,and anesthesia was induced in the high-concentration dose group.In the 5%and 125 mg/kg phenobarbital sodium groups,the mortality rate of mice was 0,the anesthesia induction time was(35.5±7.92)minutes,and the anesthesia duration was(106±39.59)minutes.In the 5%and 150 mg/kg phenobarbital sodium groups,the mortality rate of mice was 0,the anesthesia induction time was(34.83±5.27)minutes,and the anesthesia duration was(131.7±36.75)minutes.Conclusion:Phenobarbital sodium alone can provide appropriate general anesthesia in female BALB/c mice.Both the concentration and dose of phenobarbital sodium can affect the anesthetic effect.On the basis of our findings,we recommend the 5%and 125 mg/kg and 5%and 150 mg/kg concentration–dose combinations of phenobarbital sodium for anesthetizing mice according to the surgical requirement.

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

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

Studies on Anesthetic Effect of Eugenol on Juvenile Fenneropenaeus chinensis

[Objective] The aim of the study is to seek a good anesthetic to Fenneropenaeus chinensis. [Method] The anesthetic effect of eugenol to juvenile Fenneropenaeus chinensis was investigated. [Result] The juveniles could be effectively anaesthetized by 50-400 mg/L eugenol aqueous solution with temperature of 24 ℃. Within the concentration range of 50-400 mg/L, the increase of the eugenol concentration could shorten the time required for anesthesia, meanwhile could prolong the time for recovery. The recovered rate of prawn reached 100% when the eugenol concentration was lower than 200 mg/L, while the recovered rate of prawn was just 66.67% when the eugenol concentration was higher than 400 mg/L. The survival rate of prawns in test group was 100% from the observation of three consecutive days. For the specific dose, the anesthetic effect enhanced with the increase of water temperature (18-27℃). [Conclusion] Eugenol is a safe and efficient anesthetics that can be applied in genetic breeding of prawn.

Anesthesia Management in Hereditary Pheochromocytoma and Paraganglioma:Updated Insights into Clinical Features and Perioperative Care

Approximately 40% of pheochromocytoma and paraganglioma(PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau(VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2(MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1(NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team(MDT) approach is often invaluable in perioperative management.

Nurse anesthetists’perceptions and experiences of managing emergence delirium:A qualitative study

BACKGROUND This study employs a descriptive phenomenological approach to investigate the challenges anesthesia nurses face in managing emergence delirium(ED),a common and complex postoperative complication in the post-anesthesia care unit.The role of nurses in managing ED is critical,yet research on their understanding and management strategies for ED is lacking.AIM To investigate anesthetic nurses’cognition and management experiences of ED in hopes of developing a standardized management protocol.METHODS This study employed a descriptive phenomenological approach from qualitative research methodologies.Purposeful sampling was utilized to select 12 anesthetic nurses from a tertiary hospital in Shanghai as research subjects.Semi-structured interviews were conducted,and the data were organized and analyzed using Colaizzi’s seven-step analysis method,from which the final themes were extracted.RESULTS After analyzing the interview content,four main themes and eight subthemes were distilled:Inefficient cognition hinders the identification of ED(conceptual ambiguity,empirical identification),managing diversity and challenges(patientcentered safe care,low level of medical-nursing collaboration),work responsibilities and pressure coexist(heavy work responsibilities,occupational risks and stress),demand for high-quality management(expecting the construction of predictive assessment tools and prevention strategies,and pursuing standardized management processes to enhance management effectiveness).CONCLUSION Nursing managers should prioritize the needs and suggestions of nurses in order to enhance their nursing capabilities and provide guidance for standardized management processes.

Effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy

AIM : To systematically evaluate the effect of intraperitoneal local anesthetic on pain characteristics after laparoscopic cholecystectomy(LC).METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library. Randomized controlled trials in English that compared the effect of intraperitoneal administration of local anesthetics on pain with that of placebo or nothing after elective LC under general anesthesia were included. The primary outcome variables analyzed were the combined scores of abdominal, visceral, parietal, and shoulder pain after LC at multiple time points. We also extracted pain scores at resting and dynamic states.RESULTS: We included 39 studies of 3045 patients in total. The administration of intraperitoneal local anesthetic reduced pain intensity in a resting state after laparoscopic cholecystectomy: abdominal [standardized mean difference(SMD) =-0.741; 95%CI:-1.001 to-0.48, P < 0.001]; visceral(SMD =-0.249; 95%CI:-0.493 to-0.006, P = 0.774); and shoulder(SMD =-0.273; 95%CI:-0.464 to-0.082, P = 0.097). Application of intraperitoneal local anesthetic significantly reduced the incidence of shoulder pain(RR = 0.437; 95%CI: 0.299 to 0.639, P < 0.001). There was no favorable effect on resting parietal or dynamic abdominal pain.CONCLUSION: Intraperitoneal local anesthetic as an analgesic adjuvant in patients undergoing laparoscopic cholecystectomy exhibited beneficial effects on postoperative abdominal, visceral, and shoulder pain in a resting state.

Anesthetic management for small bowel enteroscopy in a World Gastroenterology Organization Endoscopy Training Center

AIM:To study the anesthetic management of patients undergoing small bowel enteroscopy in the World Gastroenterology Organization(WGO) Endoscopy Training Center in Thailand.METHODS:Patients who underwent small bowel enteroscopy during the period of March 2005 to March 2011 in Siriraj Gastrointestinal Endoscopy Center were retrospectively analyzed.The patients' characteristics,pre-anesthetic problems,anesthetic techniques,anesthetic agents,anesthetic time,type and route of procedure and anesthesia-related complications were assessed.RESULTS:One hundred and forty-four patients underwent this procedure during the study period.The mean age of the patients was 57.6 ± 17.2 years,andmost were American Society of Anesthesiologists(ASA) class Ⅱ(53.2%).Indications for this procedure were gastrointestinal bleeding(59.7%),chronic diarrhea(14.3%),protein losing enteropathy(2.6%) and others(23.4%).Hematologic disease,hypertension,heart disease and electrolyte imbalance were the most common pre-anesthetic problems.General anesthesia with endotracheal tube was the anesthetic technique mainly employed(50.6%).The main anesthetic agents administered were fentanyl,propofol and midazolam.The mean anesthetic time was 94.0 ± 50.5 min.Single balloon and oral(antegrade) intubation was the most common type and route of enteroscopy.The anesthesia-related complication rate was relatively high.The overall and cardiovascular-related complication rates including hypotension in the older patient group(aged ≥ 60 years old) were significantly higher than those in the younger group.CONCLUSION:During anesthetic management for small bowel enteroscopy,special techniques and drugs are not routinely required.However,for safety reasons anesthetic personnel need to optimize the patient's condition.

Adjuvants to local anesthetics: Current understanding and future trends

Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by itsduration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids(dexamethasone), anti-inflammatory agents(parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action(tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability(liposomal, microspheres and cyclodextrin systems) and further studies with other drugs(adenosine, neuromuscular blockers, dextrans).

Laparoscopic cholecystectomy in patients with anesthetic problems

Laparoscopic cholecystectomy is a standard operation for benign gallbladder disease. As experience with laparoscopic cholecystectomy has increased, the procedure has become possible in patients with anesthetic problems. Patients with ankylosing spondylitis or severe kyphosis represent a challenging group to anesthesiologists and laparoscopic surgeons since these diseases are associated with difficult intubation, restrictive ventilatory defects, and cardiac problems. The relatively new approach of awake fiberoptic intubation is considered to be the safest option for patients with anticipated airway difficulties. Laparoscopic cholecystectomy is usually performed under general anesthesia but considerable difficulties in anesthetic management are encountered during laparoscopic surgery; for example, hemodynamic instability may develop in patients with cardiopulmonary dysfunction due to pneumoperitoneum and position changes during the operation. Nonetheless, regional anesthesia can be considered as a valid option for patients with gallbladder disease who are poor candidates for general anesthesia due to cardiopulmonary problems. We report three cases of laparoscopic cholecystectomy successfully performed in patients with anesthetic problems that included cardiopulmonary disease, severe kyphosis, and ankylosing spondylitis.

Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice

AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice.

Anesthetic management and associated complications of peroral endoscopic myotomy:A case series

AIM To investigate the anesthetic management of peroral endoscopic myotomy(POEM) and its associated complications.METHODS This study was a single-center,retrospective,observational study comprising a case series of all patients who underwent POEM in our hospital from April 2015 to November 2016.We collected data regarding patient characteristics,anesthetic methods,surgical factors,and complications using an electronic chart.RESULTS There were 86 patients who underwent POEM in our hospital during the study period.Preoperatively,patients were maintained on a low residue diet for 48 h prior to the procedure.They were fasted of solids for 24 h before surgery.There was one case of aspiration(1.2%).During POEM,patients were positioned supine with the upper abdomen covered by a clear drape so that pneumoperitoneum could be timeously identified.In three cases,the peak airway pressure exceeded 35 cm H2 O during volume controlled ventilation with tidal volumes of 6-8 m L/kg and subsequent impairment of ventilation.These cases had been diagnosed with spastic esophageal disorders(SEDs) and the length of the muscular incision on the esophageal side was longer than normal.CONCLUSION In the anesthetic management of POEM,it is important to prevent aspiration during induction of anesthesia and to identify and treat complications associated with CO_2 insufflation.

Neuroendocrine,epigenetic,and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics(GAs).Despite advancements in refining anesthesia approaches,the effects of GAs are not fully reversible upon GA withdrawal.Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly.Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research,but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects.The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents,which are far more extensively studied than any other species.Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated.Specifically,we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities(somatic effects),but also epigenetic reprogramming of germ cells(germ cell effects).The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring,who may be affected even at levels of anesthesia that are not harmful to the exposed parents.The large number of patients who require general anesthesia,the even larger number of their future unexposed offspring whose health may be affected,and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs.In this mini review,we discuss emerging experimental findings on neuroendocrine,epigenetic,and intergenerational effects of GAs.

Exertional rhabdomyolysis and heat stroke: Beware of volatile anesthetic sedation

In view of the enormous popularity of mass sporting events such as half-marathons, the number of patients with exertional rhabdomyolysis or exercise-induced heat stroke admitted to intensive care units(ICUs) has increased over the last decade. Because these patients have been reported to be at risk for malignant hyperthermia during general anesthesia, the intensive care community should bear in mind that the same risk of life-threatening rhabdomyolysis is present when these patients are admitted to an ICU, and volatile anesthetic sedation is chosen as the sedative technique. As illustrated by the three case studies we elaborate upon, a thorough diagnostic work-up is needed to clarify the subsequent risk of strenuous exercise, and the anesthetic exposure to volatile agents in these patients and their families. Other contraindications for the use of volatile intensive care sedation consist of known malignant hyperthermia susceptibility, congenital myopathies, Duchenne muscular dystrophy, and intracranial hypertension.

Effect of Inhalational Anesthetics on Cytotoxicity and Intracellular Calcium Differently in Rat Pheochromocytoma Cells (PC12)

Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in rat pheochromocytoma cells （PC12） in a concentration- and time-dependent manner with unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum （ER） via activation of inositol 1,4,5-trisphosphate （IP3） receptors. Alzheimer＇s presenilin-1 （PS 1） mutation increased activity of IP3 receptors and therefore rendered cells vulnerable to isoflurane-induced cytotoxicity. Sevoflurane and desflurane had less ability to disrupt intracellular calcium homeostasis and thus being less potent pared the cytotoxic effects of various inhaled to cause cytotoxicity. This study examined and com-anesthetics on PC12 cells transfected with the Alzheimer＇s mutated PS 1 （L286V） and the disruption of intracellular calcium homeostasis. PC 12 cells transfected with wild type （WT） and mutated PS 1 （L286V） were treated with equivalent of 1 MAC of isoflurane, sevoflurane and desflurane for 12 h. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in cytosolic space （[Ca^2＋]c） were determined after exposing different types of cells to various inhalational anesthetics. The effects of IP3 receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in L286V PC12 cells were also determined. The results showed that isoflurane at 1 MAC for 12 h induced cytoxicity in L286V but not WT PC12 cells, which was also associated with greater and faster elevation of peak [Ca^2＋]c in L286V than in the WT cells. Xestospongin C significantly ameliorated isoflurane cytotoxicity in L286V cells, as well as inhibited the calcium release from the ER in L286V cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar cytotoxicity or elevation of peak [Ca^2＋]c in L286V PC 12 cells. These results suggested that isoflurane induced cytoxicity by partially causing abnormal calcium release from the ER via activation of IP3 receptors in L286V PC12 cells. Sevoflurane and desflurane at equivalent exposure to isoflurane did not induce similar elevation of [Ca^2＋]c or neurotoxicity in PC 12 cells transfected with the Alzheimer＇s PS 1 mutation.