Effect of Propofol Versus Sevoflurane on Erections during Narcosis in Transurethral Surgery: The PENIS Trial.

Penile erection is unwanted during transurethral interventions as it may be associated with adverse events such as impaired access, prolonged operation time, abortion of the procedure, or a need for ancillary measures to reach penis flaccidity, such as intracorporeal injection of vasoactive drugs. In recent years, anesthesia with propofol has been favored over sevoflurane for environmental reasons. To the best of our knowledge, there have been no prospective randomized clinical trials evaluating the impact of general narcosis medications on the risk of such unwanted penile erections during transurethral surgery. To fill this gap, we have planned a prospective, double-blind (surgeon and patient), single-center, randomized controlled trial. The primary outcome is the occurrence of an intraoperative penile erection. The secondary outcomes are related to the impact of the primary outcome on the surgery, such as changes in operative strategy or operation duration, abortion of the procedure, and adverse events. The plan is to randomize 200 patients undergoing transurethral surgery to receive general anesthesia with either propofol or sevoflurane. The inclusion criteria are men aged <75 yr with an International Index of Erectile Function-5 score of ≥12 points. All men fulfilling the inclusion criteria will be asked to participate. Exclusion criteria are patient characteristics associated with a higher risk of complications with the use of either propofol or sevoflurane. Randomization and treatment allocation will occur after patients give consent. The results will be statistically analyzed using a logistic regression model. This research has received ethical clearance from the local ethics committee (KEK code 2023-01682). The trial is registered on the Swiss National Clinical Trials Portal (SNCTP000005681) and on ClinicalTrial.gov (NCT06378645).

Effects of prophylactic nalbuphine on emergence agitation and postoperative pain in pediatric patients undergoing ENT surgery with sevoflurane anesthesia.

Background: Emergence agitation (EA) is a common complication in the pediatric population. This study aimed to investigate the effect of the prophylactic nalbuphine on EA in pediatric patients receiving sevoflurane anesthesia. Methods: The children undergoing ear, nose, and throat (ENT) surgery were administered 0.2 mg/kg nalbuphine (the nalbuphine group) or the same volume of normal saline (the control group) 5 min before the end of the surgery. The extubating time, time to eye-opening and duration of the post-anesthesia care unit (PACU) were recorded. Heart rate and blood pressure were monitored before and 5 min after nalbuphine administration. Pain was assessed using Face Legs Activity Cry and Consolability (FLACC) scales, and the drug-related postoperative complications (e.g., EA, delayed awakening, nausea and vomiting, and respiratory depression) were recorded. Results: One-hundred and thirty pediatric patients were randomly divided into nalbuphine and control groups (n = 65). The nalbuphine group showed a significantly lower incidence of EA than the control group (20% vs. 46.2%, P = 0.002). No significant differences between the two groups were observed in heart rate and blood pressure 5 min after nalbuphine administration (P > 0.05). No significant differences were observed between the two groups regarding extubating time, time to eye-opening, and duration of PACU. The FLACC scales demonstrated lower values in the nalbuphine group than in the control group during the initial 4 h after the surgery. However, the FLACC scales showed similar values between 5 and 12 h after the surgery. Conclusions: In summary, the results of this study demonstrated that prophylactic natbuphine could minimize the incidence of EA in pediatric patients following ENT surgery without increasing the extubating time and PACU duration. Clinical Trial Registration: http://www.chictr.org.cn, identifier [ChiCTR2300070046].

The activity of suprahyoid muscles during sevoflurane-induced gasping in mice.

Sevoflurane-induced gasping in mice involves an enormous increase in inspiratory effort, mandibular movement, and a marked decrease in respiratory frequency (fR). We examined differences in breathing patterns and electromyogram activity (EMGSH) of the suprahyoid muscles (SHMs) during eupnea under 3.2% (1 MAC: minimum alveolar concentration) sevoflurane inhalation and sevoflurane-induced gasping under 6.5% (2 MAC) sevoflurane inhalation in eight spontaneously breathing, tracheally intubated, adult mice. We found that the phasic EMGSH is obtained only during inspiration in eupnea and gasping and that integrated EMGSH increases more, as a percent of baseline (% baseline) than tidal volume (VT) during gasping (median [interquartile range]; integrated EMGSH: 720 [425-1965] vs. VT: 300 [238-373], P<0.05). We also found that the onset of EMGSH precedes the start of airflow while maintaining a bell-shaped EMGSH contour, which characterizes the EMG of upper airway dilator (UAD) muscles during eupnea and gasping. Vigorous respiratory-related mandibular movements were never observed during eupnea but were observed in seven of 8 mice during sevoflurane-induced gasping. Our observations indicate that SHMs act as a preferentially activating UAD muscle, contributing to the development of mandibular respiratory movements.

How Much Time Do Focal Treatments for Retinoblastoma Add to Anesthetic Exposure?

Introduction: Children with retinoblastoma have anesthesia for exams and treatment, but there is little information about how long treatment interventions (laser, cryotherapy, and intravitreal injections) add to routine exams under anesthesia (EUA). This information would be useful for planning operating room schedules, staff schedules, family expectations, and billing. Methods: A retrospective, single-center, Institutional Review Board (IRB) approved review of anesthesia duration for retinoblastoma children undergoing EUA with laser, cryotherapy, or intravitreal injections performed at MSK between January 2019 and November 2023. Results: Three hundred eight patients had 2,399 EUAs. The average EUA lasted 24.3 min (range 7-77 min) when no interventions were done. Laser photocoagulation added an average of 18.9 min (range 19-77 min), cryotherapy 26.1 min (range 27-75 min), and intravitreal injection 23.5 min (range 10-71 min) to the basic EUA time. Bilateral laser treatments took 8 min longer than unilateral treatments. Conclusion: EUAs for children with retinoblastoma can be performed relatively quickly. Interventions such as laser, cryotherapy, or intravitreal injections roughly double the time under anesthesia but in some cases can take much longer (>1 h).

ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on gastric cancer cell malignancy by regulating the N6-methyladenosine modification of the lncRNA DLX6-AS1.

Sevoflurane, an inhalation anesthetic, has been shown to suppress cancer development. In this study, we investigated the specific mechanisms involving sevoflurane, zinc-finger CCCH-type containing 13 (ZC3H13), and lncRNA DLX6-AS1 in gastric cancer (GC) progression, focusing on the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs). We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to measure the levels of ZC3H13 and lncRNA DLX6-AS1 in GC tissues and cells. Furthermore, we conducted Cell Counting Kit-8, colony formation, Transwell, and tumor xenograft assays to evaluate changes in GC cell malignancy following cell transfection and sevoflurane treatment. Additionally, actinomycin D, methylated RNA immunoprecipitation, and qRT-PCR assays were performed to examine the regulatory effects of ZC3H13 on the DLX6-AS1 m6A modification. We detected elevated levels of ZC3H13 in GC samples, while ZC3H13 silencing inhibited GC cell proliferation, migration, and invasion. Silencing ZC3H13 also enhanced the inhibitory effects of sevoflurane on GC cell malignancy. Moreover, we found that the increased expression of DLX6-AS1 in GC cells could be suppressed by ZC3H13 through the mediation of the m6A modification of DLX6-AS1, thereby reducing DLX6-AS1 stability. In conclusion, ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on GC cell malignancy by inducing DLX6-AS1 m6A modification. Our findings may help identify potential therapeutic targets for the treatment of GC.

Triple Anesthesia: Combining Sevoflurane, Propofol, and Remimazolam for General Anesthesia in a Case Series.

There is an ongoing quest for an ideal uniform anesthesia regimen that adequately covers all nociceptive stimuli preventing hypertension and tachycardia while minimizing hypotension and the need for antihypotensive drugs. Recently, the ultra-short-acting benzodiazepine remimazolam was approved for the induction and maintenance of general anesthesia. Combining remimazolam with sevoflurane and propofol may combine the antiemetic properties of propofol, the depressing (immobilizing) effect on spinal motor neurons of sevoflurane, and the hemodynamic stability afforded by remimazolam, making it an attractive addition to the armamentarium of anesthetic agents. We describe five patients in whom general anesthesia was maintained with this triple combination, along with multimodal analgesia. All patients maintained hemodynamic stability at sufficient hypnotic depth, with no observable movement during surgery or episodes of cardiac arrhythmias.

Impact of Sevoflurane and Propofol on Perioperative Respiratory Adverse Events in Pediatrics: A Systematic Review and Meta-analysis.

PURPOSE: Perioperative respiratory adverse events continue to pose significant challenges in pediatric anesthesia. Research has hinted at a lower incidence of these complications in children anesthetized with propofol than sevoflurane. This study aimed to assess and compare respiratory complications in children undergoing general anesthesia with either sevoflurane or propofol during surgery. DESIGN: Systematic review and meta-analysis. METHODS: We conducted comprehensive searches of the PubMed, Embase, and Cochrane Library databases and manual searches to identify pertinent randomized controlled trials (RCTs) published up to August 19, 2023. The Cochrane risk assessment tool was employed to evaluate the risk of bias in the selected studies. The pooled analysis of relevant data compared respiratory complications, vomiting, agitation, anesthesia duration, extubation time, and recovery time in pediatric patients undergoing anesthesia with sevoflurane and propofol. FINDINGS: A total of 17 RCTs, containing 1,758 pediatric participants, were included and analyzed. Respiratory adverse events were examined, encompassing laryngospasm, apnea, cough, and SpO2. In comparison to sevoflurane, children subjected to propofol anesthesia demonstrated a significant reduction in the risk of laryngospasm (P = .001), vomiting (P < .001), and agitation (P = .029). Especially in patients receiving laryngeal mask airway, propofol anesthesia significantly reduced the incidence of laryngospasm (P = .003) and agitation (P < .001). At the same time, they exhibited an increased risk of apnea (P = .039). Notably, no statistically significant disparities were observed between sevoflurane and propofol concerning cough, SpO2 < 95%, anesthesia time, extubation time, and recovery time. Administration of propofol following sevoflurane anesthesia did not significantly impact the occurrence of vomiting or the recovery time. CONCLUSIONS: While propofol presents an elevated risk of apnea, it concurrently yields a significant reduction in laryngospasm, vomiting, and agitation. Consequently, propofol emerges as a favorable anesthetic option for pediatric patients.

The bioenergetics of traumatic brain injury and its long-term impact for brain plasticity and function.

Mitochondria provide the energy to keep cells alive and functioning and they have the capacity to influence highly complex molecular events. Mitochondria are essential to maintain cellular energy homeostasis that determines the course of neurological disorders, including traumatic brain injury (TBI). Various aspects of mitochondria metabolism such as autophagy can have long-term consequences for brain function and plasticity. In turn, mitochondria bioenergetics can impinge on molecular events associated with epigenetic modifications of DNA, which can extend cellular memory for a long time. Mitochondrial dysfunction leads to pathological manifestations such as oxidative stress, inflammation, and calcium imbalance that threaten brain plasticity and function. Hence, targeting mitochondrial function may have great potential to lessen the outcomes of TBI.

Novel technique of switching TIVA and sevoflurane during epilepsy surgery for combined intraoperative motor evoked potentials monitoring and electrocorticography: an illustrative case report.

BACKGROUND: During epilepsy surgery, it is equally important to record electrocorticography (ECoG) for detecting epileptogenic activity and guiding brain resection, and to evaluate neuromonitoring data, particularly motor evoked potentials (MEP), for avoidance of postoperative neurological complications. However, sevoflurane, which is commonly used during recording of ECoG, may attenuate the MEP response. It enforces anesthesiologists and neurosurgeons to select one anesthetic agent over another, facilitating either ECoG or MEP monitoring. CASE PRESENTATION: In the presented case of a 20-year-old man, who underwent surgery for temporal lobe epilepsy, a novel technique of neuroanesthesia was introduced, integrating initial induction of the total intravenous anesthesia (TIVA) with propofol (effect-site concentration, 2.3-3.0 µg/ml), its subsequent switching to sevoflurane (end-tidal concentration, 2.5%) for ECoG recording, and further change back to TIVA for MEP monitoring during brain resection. CONCLUSIONS: Intraoperative switch of anesthetic agents according to specific intraoperative requirements may be useful for cases of brain surgery requiring both ECoG recordings and MEP monitoring.

Different ethanol exposure durations affect cytochrome P450 2E1-mediated sevoflurane metabolism in rat liver.

BACKGROUND: Chronic alcohol users often exhibit an increased minimum alveolar concentration (MAC) of sevoflurane, yet the specific mechanism remains unclear. It has been reported that ethanol exposure can upregulate the protein expression and enzyme activity of cytochrome P450 2E1 (CYP2E1). CYP2E1 is a key enzyme that converts 2-5% of sevoflurane into equimolar amounts of hexafluoroisopropanol (HFIP) and F-. This study aims to explore whether ethanol exposure could alter sevoflurane metabolism through CYP2E1 modulation, potentially explaining the increased MAC observed in alcohol users. METHODS: Eighty adult male Sprague-Dawley (SD) rats were randomly divided into two groups and received either 50% ethanol (dose: 3 g/kg) or 0.9% saline twice daily by gavage. After 1, 2, 3, and 4 weeks of gavage, ten rats were randomly selected from each group to undergo 1-hour anesthesia with 2.3% sevoflurane. Blood samples were collected after anesthesia to measure the concentration of free HFIP using gas chromatography. Additionally, the left lobe tissue of the liver was collected for the analysis of CYP2E1 protein expression by Western blot and CYP2E1 enzyme activity by colorimetric assay. Correlations between these parameters were analyzed using Pearson's correlation. RESULTS: In the ethanol group, CYP2E1 expression, activity, and the concentration of free HFIP were significantly higher at all time points compared to the control group (P < 0.05), except for protein expression in the first week (P > 0.05). Within-group comparisons indicated no significant changes in any of the parameters for the control group (P > 0.05). In the ethanol group, there was no difference in free HFIP concentration between the first and second weeks (P > 0.05), but a significant increase was observed in the third and fourth weeks (P < 0.01); protein expression and enzyme activity significantly varied over time, especially showing a notable increase from the first to the third and fourth weeks (P < 0.05). Correlation analysis revealed strong positive correlations between free HFIP concentration and CYP2E1 activity (r = 0.7898), free HFIP concentration and CYP2E1 expression (r = 0.8418), and CYP2E1 activity and expression (r = 0.8740), all with P < 0.001. CONCLUSIONS: Ethanol exposure increased both the expression and enzymatic activity of CYP2E1, consequently enhancing the metabolism of sevoflurane.

Cognitive impairment induced by sevoflurane anesthesia is mediated by the cholinergic system after gastrointestinal surgery in older patients: A randomized, controlled trial.

Delayed neurocognitive recovery after surgery is associated with increased morbidity and mortality. However, its mechanism of action remains controversial and complex. A prospective, double-blind, randomized controlled trial was performed at the Affiliated Hospital of Zunyi Medical University. Older patients (aged 65 years and older) who underwent gastrointestinal surgery were randomly divided into sevoflurane-based or propofol-based anesthesia groups. The Mini-Mental State Examination was performed to evaluate cognitive function. Peripheral venous blood was collected to test the levels of choline acetyltransferase and acetylcholinesterase. A total of 75 patients were enrolled and 30 patients in each group completed the study. On Day 1 postoperation, patients in the sevoflurane group showed worse performance on the Mini-Mental State Examination than patients in the propofol group. Lower blood choline acetyltransferase concentrations and higher acetylcholinesterase concentrations were observed in patients who had sevoflurane anesthesia than in patients who had propofol anesthesia 1 day postoperative. At 3 days postoperation, patients with sevoflurane- or propofol-based general anesthesia did not differ regardless of Mini-Mental State Examination score or choline acetyltransferase and acetylcholinesterase levels. Sevoflurane-based anesthesia has short-term delayed neurocognitive recovery in older surgical patients, which may be related to central cholinergic system degeneration.

The Role of the SIRT1-mTOR Signaling Pathway in Regulating Autophagy in Sevoflurane-Induced Apoptosis of Fetal Rat Brain Neurons.

BACKGROUND: Isoflurane is a commonly used general anesthetic widely employed in clinical surgeries. Recent studies have indicated that isoflurane might induce negative impacts on the nervous system, notably by triggering neuronal apoptosis. This process is pivotal to the development and emergence of neurological disorders; its misregulation could result in functional deficits and the initiation of diseases within nervous system. However, the potential molecular mechanism of isoflurane on the neuronal apoptosis remains fully unexplored. This study aims to investigate the regulatory role of the sirtuin 1-mechanistic target of rapamycin (SIRT1-mTOR) signaling pathway in autophagy during isoflurane-induced apoptosis of fetal rat brain neuronal cells. METHODS: Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, real-time quantitative polymerase chain reaction (qPCR), and Western blot were utilized to evaluate the apoptotic status of hippocampal tissue cells in fetal mice after sevoflurane exposure. Our further investigation was commenced with flow cytometry, immunofluorescence, qPCR, and Western blot to determine the impact of autophagy on sevoflurane-induced apoptosis in these neurons. On the other hand, we conducted an additional set of analyses, including flow cytometric analysis, qPCR, and Western blot, to further elucidate the neuroprotective potential of autophagy in neural cells of fetal mice subjected to sevoflurane-induced apoptosis. RESULTS: Our findings indicated that a 3% sevoflurane treatment led to a significant rise in apoptosis among fetal rat hippocampal tissue cells and neurons. Levels of apoptosis-associated proteins, cleaved-caspase-3 and Bcl-2 associated X protein (Bax), were found to be markedly higher, coinciding with an enhancement in autophagy as evidenced by increased microtubule-associated proteins 1A/1B-light chain 3 (LC3) and decreased p62 expression. Concurrently, there was a notable up-regulation of sirtuin 1 (SIRT1) and a down-regulation of mechanistic target of rapamycin (mTOR) expression. In conclusion, our research elucidated the pivotal function of cellular autophagy in an apoptosis induced by sevoflurane in fetal rat nerve cells. Through experimental manipulation, we observed that interference with SIRT1 resulted in a reduction of both cleaved-caspase-3 and Bax levels. This intervention also beget a diminished expression of the autophagy-associated factor LC3 and an up-regulation of p62. Furthermore, inhibition against mTOR reversed the effects induced by SIRT1 interference, suggesting a complex interplay amid these regulatory pathways. CONCLUSIONS: SIRT1 possesses a capacity to modulate apoptosis in the hippocampal neurons of fetal rats triggered by sevoflurane, with mTOR functioning as an inhibitory factor within this signaling pathway.

Evaluation of the Effect of Different Inhalation Agents on Ovaries with Hyperthermic Intraperitoneal Chemotherapy: An Experimental Study.

Background and Objectives: Cisplatin is a chemotherapeutic drug that is frequently used with hyperthermic intraperitoneal chemotherapy (HIPEC). Cisplatin-induced gonadotoxicity leads to a depletion of the ovarian reserve, causing premature ovarian insufficiency. This study aimed to investigate the impact of hyperthermia on cisplatin-induced ovarian toxicity and to determine whether sevoflurane or desflurane could be a more appropriate choice of anesthetic for reducing ovarian toxicity in HIPEC procedures. Materials and Methods: A total of 24 New Zealand rabbits were randomly divided into 4 groups as follows: Group H: HIPEC (cisplatin 7 mg/kg), Group HS: HIPEC (cisplatin 7 mg/kg) + 3% sevoflurane (2 h), Group HD: HIPEC (cisplatin 7 mg/kg) + 6% desflurane (2 h), and Group C: Control (Saline). Two catheters were placed in the abdominal cavity, the upper and lower quadrants. The perfusate was heated to 42 °C and given intraperitoneally for 90 min at a rate of 4 mL/min by catheters. Ovarian tissues were collected for Hematoxylin and Eosin staining and immunohistochemical analysis. Results: The primary follicle number was significantly decreased in Group H and HD compared to the C group (p < 0.05). Bax expression was high in Group H, according to all groups (p < 0.0001). Bax expression significantly decreased after sevoflurane, compared to group H (p = 0.012). The bcl-2 expression decreased in all groups compared to the C group. Bcl-2 expression was increased with sevoflurane compared to the H group (p = 0.001). Caspase 3 and p53 expression increased in all groups compared to the C group. p53 expression was decreased with sevoflurane and desflurane compared to the H group (p = 0.002, p = 0.008, respectively). Conclusions: The application of cisplatin with the intraoperative HIPEC method caused ovarian damage. According to our results, sevoflurane anesthesia could be a better option in mitigating cell death I the n ovarian reserve (follicle count) and apoptosis in the HIPEC procedures. We think that our findings should be supported by large series of clinical and experimental studies.

Effects of Cohabitation on Neurodevelopmental Outcomes in Rats Discordant for Neonatal Exposure to Sevoflurane.

Background: Having a sibling with autism spectrum disorder is a risk factor for autism spectrum disorder. We used a rat model in which the general anesthetic sevoflurane (SEVO) induces autism spectrum disorder-like neurodevelopmental abnormalities to test whether they can be transmitted via cohabitation. Methods: Male rat pups from several litters were mixed and randomized to 3 new litter types: SEVO-exposed (SEVO), SEVO-unexposed (control), and equal numbers of SEVO-exposed and SEVO-unexposed (MIXED). After weaning, rats in experiment 1 were housed with littermates in SEVO, control, and MIXED (MIXED-exposed and MIXED-unexposed) pairs. In experiment 2, MIXED-exposed and MIXED-unexposed rats were paired with an unfamiliar naïve cagemate. Corticosterone levels, gene expression, central inflammatory markers (experiment 1), and behavior and corticosterone levels (experiment 2) were assessed in adulthood. Results: In experiment 1, compared with control rats, SEVO rats exhibited abnormalities in the hypothalamic-pituitary-adrenal axis, inflammatory markers, oxytocin, arginine vasopressin, and DNA methylation systems. Almost all these measures in MIXED-exposed and MIXED-unexposed rats were statistically indistinguishable from and similar to those in SEVO or control rats, with most measures in MIXED rats being similar to those in SEVO rats. Experiment 2 showed that pairing with unfamiliar, naïve rats after weaning caused MIXED-unexposed and MIXED-exposed rats' behavior to be no different from that of control and SEVO rats, respectively; however, the 2 groups of MIXED rats also did not differ from each other. Conclusions: These findings suggest that neurodevelopmental abnormalities can be transmitted to otherwise healthy individuals through interactions during cohabitation; however, subsequent pairing with unfamiliar, naïve cohabitants may weaken this interaction effect.

This study was driven by the results of human studies that found poorer neurocognitive performance than expected in both twins, even though only one of the twins had early-life exposure to general anesthesia. We evaluated whether rats housed together in the same cage but discordant for neonatal exposure to the general anesthetic sevoflurane share similar neurodevelopmental abnormalities in adulthood. The gene expression, neuroendocrine, neuroinflammatory marker, and behavioral measurements revealed that cohoused neonatally sevoflurane-exposed and sevoflurane-unexposed cagemates exhibited similar deficiencies. These findings suggest that in studies of anesthesia-induced neurodevelopmental abnormalities in particular, and neurocognitive development in general, interactions between cohabitants should be considered as a factor that may influence outcomes.

Sevoflurane anesthesia during late gestation induces cognitive disorder in rat offspring via the TLR4/BDNF/TrkB/CREB pathway.

Sevoflurane (Sevo) is widely used for general anesthesia during pregnancy. Emerging evidence indicates that maternal Sevo exposure can trigger developmental neurotoxicity in the offspring. Nonetheless, the underlying mechanisms need further investigation. Pregnant Sprague-Dawley rats on gestational day 18 were exposed to 3.5% Sevo to induce the rat model of neurotoxicity. TAK-242, a TLR4 inhibitor, was administrated to inhibit the signaling transduction. Hippocampal tissues of rat offspring were harvested for immunohistochemical staining, TUNEL staining, Western blotting, ELISA, and measurement of oxidative stress-related markers. Serum samples were collected to evaluate lipid metabolism-associated factors. Morris water maze was implemented to test the cognitive function of offspring rats. Rat hippocampal neurons were isolated to elucidate the effect of TAK-242 on the BDNF/TrkB/CREB signaling in vitro. The results showed that maternal Sevo exposure during the third trimester induced neuroinflammation, lipid metabolism disturbance, and oxidative stress, and impaired the spatial learning and memory of rat offspring. Sevo upregulated TLR4 and impeded BDNF/TrkB/CREB signaling transduction in the hippocampus of rat offspring; TAK-242 administration reversed these effects. In conclusion, Sevo anesthesia during late gestation impairs the learning and memory ability of rat offspring possibly by promoting neuroinflammation and disturbing lipid metabolism via the TLR4/BDNF/TrkB/CREB pathway.

Berberine Alleviates Sevoflurane Anesthesia-Induced Cognitive Dysfunction in Neonatal Mice via Regulating CREB1.

BACKGROUND: Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed to investigate the effects of berberine on cognitive dysfunction induced by sevoflurane anesthesia and its potential mechanisms. METHODS: In the in vivo study, neonatal mice were subjected to sevoflurane anesthesia to induce cognitive dysfunction. The cognitive function of the neonatal mice was evaluated using the Morris water maze test, open field test, and tail suspension test. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess the levels of inflammatory factors. Immunohistochemistry (IHC) was conducted to detect ionized calcium-binding adaptor molecule 1 (IBA-1)-positive cells and cleaved caspase-3-positive cells in the hippocampus of the neonatal mice. Western blotting was used to measure the levels of cyclic adenosine monophosphate (cAMP) response element-binding protein 1 (CREB1) in hippocampal tissues and neurons. Hippocampal neurons were isolated from the hippocampus of neonatal mice. These neurons were treated with berberine or subjected to cell transfection. The cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were conducted to measure cell viability and apoptosis of hippocampal neurons in vitro. RESULTS: Berberine significantly attenuated sevoflurane-induced cognitive impairment and inflammation in neonatal mice (p < 0.05 or p < 0.01). Additionally, berberine reduced sevoflurane-triggered neuronal apoptosis in the hippocampus of neonatal mice (p < 0.01). Sevoflurane markedly decreased CREB1 expression in the hippocampus of neonatal mice (p < 0.01), which was elevated by berberine treatment (p < 0.01). Mechanistically, sevoflurane significantly suppressed cell viability and promoted cell apoptosis of hippocampal neurons (p < 0.0001 or p < 0.01), which were mitigated by berberine (p < 0.05, p < 0.01, or p < 0.001). Furthermore, berberine significantly elevated CREB1 expression in sevoflurane-treated hippocampal neurons (p < 0.01). The beneficial effects of berberine on cell viability and apoptosis in sevoflurane-treated hippocampal neurons were blocked by CREB1 depletion (p < 0.001). CONCLUSION: Our results demonstrated that CREB1 was significantly decreased in the hippocampus of sevoflurane-treated neonatal mice in vivo and in sevoflurane-treated hippocampal neurons in vitro. This decrease was mitigated by berberine treatment. Moreover, berberine improved sevoflurane anesthesia-induced cognitive impairment in neonatal mice by attenuating neuronal inflammation and apoptosis in vivo. The inhibitory effects of berberine on sevoflurane-induced cell apoptosis were reversed by CREB1 downregulation. These findings indicate that berberine protects against sevoflurane anesthesia-induced cognitive impairment by reducing apoptosis of hippocampal neurons, partially through increasing CREB1 expression.

Hypothermia and rewarming times during general anesthesia in Hispaniolan Amazon parrots (Amazona ventralis): A comparative study between isoflurane, sevoflurane and desflurane.

OBJECTIVE: To evaluate induced hypothermia and rewarming times in Hispaniolan Amazon parrots (HAP; Amazona ventralis) anesthetized using isoflurane, sevoflurane or desflurane, and to describe selected cardiovascular and respiratory effects. STUDY DESIGN: Randomized, balanced, crossover experimental study. ANIMALS: A group of 12 adult HAP. METHODS: Parrots were premedicated with intramuscular butorphanol (0.5 mg kg-1) and anesthetized with the three inhalants with a 7 day washout period between events. Anesthesia was induced using isoflurane at 4 vol%, sevoflurane at 6 vol% or desflurane 12 vol% carried in oxygen, delivered via face mask. After orotracheal intubation, anesthesia maintenance was with end-tidal concentrations of 1.4-2% (Fe'Iso), 2.4-3% (Fe'Sevo) and 8.5-9.2% (Fe'Des). Hypothermia was defined as an esophageal temperature (BT) below 37.8 °C. External heat support was provided when BT dropped to 37.5 °C. Time for temperature decrease from 38.9 °C to 37.5 °C (T1), time to first increase in BT above 37.5 °C (T2) and time from external heat support to achieving 38.9 °C (T3) were recorded and compared via Friedman tests with post hoc Dunn's test. Heart rate, respiratory rate and end-tidal carbon dioxide, amongst other variables, were evaluated. RESULTS: All inhalants caused hypothermia (T1): isoflurane, 12 (2-37) minutes [median (range)]; sevoflurane, 12 (4-18) minutes; desflurane, 11.5 (6-24) minutes, with no significant differences between treatments (p > 0.05). T2 was significantly (p = 0.042) longer for sevoflurane than for desflurane but not isoflurane. Transient apnea was observed with all inhalants, including 25% of birds anesthetized with sevoflurane. Second-degree atrioventricular block and ventricular escape beats occurred with all inhalants with hypothermia potentially exacerbating cardiac arrhythmias. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia rapidly developed in butorphanol-sedated HAP anesthetized using isoflurane, sevoflurane or desflurane. Sevoflurane prolonged warming time. Hypothermia may be associated with an increased likelihood of bradyarrhythmia in parrots anesthetized with inhalants.

Novel insights into sevoflurane-induced developmental neurotoxicity mechanisms.

Aim: This study explores Sevoflurane (Sevo)-induced neurotoxicity mechanisms in neonates through transcriptome sequencing and models.Methods: Seven-day-old mice were exposed to 3% Sevo, and hippocampal tissue was collected for analysis of differentially expressed lncRNAs and mRNAs compared with normal mice. MiR-152-3p was selected, and the interaction between H19, USP30, and miR-152-3p was explored in BV2 microglial cells and mouse hippocampal neurons.Results: Sevo disrupts mitochondrial autophagy via USP30 upregulation, exacerbating neurotoxicity and activating NLRP1 inflammasome-mediated inflammation.Conclusion: Sevo neurotoxicity is mediated through the H19/miR-152-3p/USP30 axis, implicating microglial regulation of neuronal pyroptosis.

[Box: see text].

Anaesthetics disrupt complex I-linked respiration and reverse the ATP synthase.

The mechanism of volatile general anaesthetics has long been a mystery. Anaesthetics have no structural motifs in common, beyond lipid solubility, yet all exert a similar effect. The fact that the inert gas xenon is an anaesthetic suggests their common mechanism might relate to physical rather than chemical properties. Electron transfer through chiral proteins can induce spin polarization. Recent work suggests that anaesthetics dissipate spin polarization during electron transfer to oxygen, slowing respiration. Here we show that the volatile anaesthetics isoflurane and sevoflurane specifically disrupt complex I-linked respiration in the thoraces of Drosophila melanogaster, with less effect on maximal respiration. Suppression of complex I-linked respiration was greatest with isoflurane. Using high-resolution tissue fluorespirometry, we show that these anaesthetics simultaneously increase mitochondrial membrane potential, implying reversal of the ATP synthase. Inhibition of ATP synthase with oligomycin prevented respiration and increased membrane potential back to the maximal (LEAK state) potential. Magnesium-green fluorescence predicted a collapse in ATP availability following a single anaesthetic dose, consistent with ATP hydrolysis through reversal of the ATP synthase. Raised membrane potential corresponded to a rise in ROS flux, especially with isoflurane. Anaesthetic doses causing respiratory suppression were in the same range as those that induce anaesthesia, although we could not establish tissue concentrations. Our findings show that anaesthetics suppress complex I-linked respiration with concerted downstream effects. But we cannot explain why only mutations in complex I, and not elsewhere in the electron-transfer system, confer hypersensitivity to anaesthetics.

Links between mutations in functionally separate arms of mitochondrial complex I and responses to volatile anesthetics.

BACKGROUND: Individuals with mitochondrial defects, especially those in Complex I of the electron transport chain, exhibit behavioral hypersensitivity and toxicity to volatile anesthetics. In Drosophila melanogaster, mutation of ND23 (NDUFS8 in mammals), which encodes a subunit of the matrix arm of Complex I, sensitizes flies to toxicity from isoflurane but not an equipotent dose of sevoflurane. Also, in ND23 flies, both anesthetics activate expression of stress response genes, but to different extents. Here, we investigated the generality of these findings by examining flies mutant for ND2 (ND2 in mammals), which encodes a subunit of the membrane arm of Complex I. METHODS: The serial anesthesia array was used to expose ND2del1 and ND2360114 flies to precise doses of isoflurane, sevoflurane, and oxygen. Behavioral sensitivity was assessed by a climbing assay and toxicity by percent mortality within 24 h of exposure. Changes in expression were determined by qRT-PCR of RNA isolated from heads at 0.5 h after anesthetic exposure. RESULTS: Unlike ND2360114, ND2del1 did not affect behavioral sensitivity to isoflurane or sevoflurane. Furthermore, sevoflurane in hyperoxia as well as anoxia caused mortality of ND2del1 but not ND2360114 flies. Finally, the mutations had different effects on induction of stress response gene expression by the anesthetics. CONCLUSION: Mutations in different arms of Complex I resulted in different behavioral sensitivities and toxicities to isoflurane and sevoflurane, indicating that (i) the anesthetics have mechanisms of action that involve arms of Complex I to different extents and (ii) the lack of behavioral hypersensitivity does not preclude susceptibility to anesthetic toxicity.