Effect of reducing isoflurane level on glucosamine uptake in the mouse brain during magnetic resonance imaging studies.

Anesthesia is often required during magnetic resonance imaging (MRI) examinations in animal studies. Anesthetic drugs differ in their capacity to interfere with homeostatic mechanisms responsible for glucose metabolism in the brain, which may create a constraint in the study design. Recent studies suggest that the chemical exchange saturation transfer (CEST) MRI scanning technique can detect localized metabolic changes in rodent brains induced by the uptake of glucose or its analogs; however, most of these studies do not account for the impact of anesthesia type on the brain metabolism. Herein, we aimed to evaluate the effect of reduced isoflurane levels on the preclinical imaging of glucosamine (GlcN) uptake in healthy mouse brains to establish optimal conditions for future brain imaging studies using the CEST MRI technique. The commonly used anesthesia protocol for longitudinal MRI examinations using 1.5% isoflurane level was compared to that using a mixture of low isoflurane (0.8%) level combined with midazolam (2 mg/kg, SC). Magnetization transfer ratio asymmetry (MTRasym) and area under the curve (AUC) analyses were used to characterize GlcN signals in the brain. The results indicated that mice injected with GlcN and anesthetized with 1.5% isoflurane exhibited low and insignificant changes in the MTRasym and AUC signals in the frontal cortex, whereas mice administered with 0.8% isoflurane combined with midazolam demonstrated a significant increase in these signals in the frontal cortex. This study highlights the diverse GlcN metabolic changes observed in mouse brains under variable levels of isoflurane anesthesia using the CEST MRI method. The results suggest that it is feasible to maintain anesthesia with low-dose isoflurane by integrating midazolam, which may enable the investigation of GlcN uptake in the brain. Thus, reducing isoflurane levels may support studies into mouse brain metabolism using the CEST MRI method and should be considered in future studies.

Mapping general anesthesia states based on electro-encephalogram transition phases.

Cortical electro-encephalography (EEG) served as the clinical reference for monitoring unconsciousness during general anesthesia. The existing EEG-based monitors classified general anesthesia states as underdosed, adequate, or overdosed, lacking predictive power due to the absence of transition phases among these states. In response to this limitation, we undertook an analysis of the EEG signal during isoflurane-induced general anesthesia in mice. Adopting a data-driven approach, we applied signal processing techniques to track θ- and δ-band dynamics, along with iso-electric suppressions. Combining this approach with machine learning, we successfully developed an automated algorithm. The findings of our study revealed that the dampening of the δ-band occurred several minutes before the onset of significant iso-electric suppression episodes. Furthermore, a distinct γ-frequency oscillation was observed, persisting for several minutes during the recovery phase subsequent to isoflurane-induced overdose. As a result of our research, we generated a map summarizing multiple brain states and their transitions, offering a tool for predicting and preventing overdose during general anesthesia. The transition phases identified, along with the developed algorithm, have the potential to be generalized, enabling clinicians to prevent inadequate anesthesia and, consequently, tailor anesthetic regimens to individual patients.

Sedation with propofol and isoflurane differs in terms of microcirculatory parameters: A randomized animal study using dorsal skinfold chamber mouse model.

OBJECTIVE: This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions. MATERIAL AND METHODS: Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed. RESULTS: In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001). CONCLUSIONS: Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.

Effect of isoflurane anaesthetic time on ocular a-scan ultrasonography measures and their relationship to age and OCT measures in the Guinea pig.

A-scan ultrasonography enables precise measurement of internal ocular structures. Historically, its use has underpinned fundamental studies of eye development and aberrant eye growth in animal models of myopia; however, the procedure typically requires anaesthesia. Since anaesthesia affects intra-ocular pressure (IOP), we investigated changes in internal ocular structures with isoflurane exposure and compared measurements with those taken in awake animals using optical coherence tomography (OCT). Continuous A-scan ultrasonography was undertaken in tri-coloured guinea pigs aged 21 (n = 5), 90 (n = 5) or 160 (n = 5) days while anaesthetised (up to 36 min) with isoflurane (5% in 1.5L/min O2). Peaks were selected from ultrasound traces corresponding to the boundaries of the cornea, crystalline lens, retina, choroid and sclera. OCT scans (Zeiss Cirrus Photo 800) of the posterior eye layers were taken in 28-day-old animals (n = 19) and compared with ultrasound traces, with choroid and scleral thickness adjusted for the duration of anaesthesia based on the changes modelled in 21-day-old animals. Ultrasound traces recorded sequentially in left and right eyes in 14-day-old animals (n = 30) were compared, with each adjusted for anaesthesia duration. The thickness of the cornea was measured in enucleated eyes (n = 5) using OCT following the application of ultrasound gel (up to 20 min). Retinal thickness was the only ultrasound internal measure unaffected by anaesthesia. All other internal distances rapidly changed and were well fitted by exponential functions (either rise-to-max or decay). After 10 and 20 min of anaesthesia, the thickness of the cornea, crystalline lens and sclera increased by 17.1% and 23.3%, 0.4% and 0.6%, and 5.2% and 6.5% respectively, whilst the anterior chamber, vitreous chamber and choroid decreased by 4.4% and 6.1%, 0.7% and 1.1%, and 10.7% and 11.8% respectively. In enucleated eyes, prolonged contact of the cornea with ultrasound gel resulted in an increase in thickness of 9.3% after 10 min, accounting for approximately half of the expansion observed in live animals. At the back of the eye, ultrasound measurements of the thickness of the retina, choroid and sclera were highly correlated with those from posterior segment OCT images (R2 = 0.92, p = 1.2 × 10-13, R2 = 0.55, p = 4.0 × 10-4, R2 = 0.72, p = 5.0 × 10-6 respectively). Furthermore, ultrasound measures for all ocular components were highly correlated in left and right eyes measured sequentially, when each was adjusted for anaesthetic depth. This study shows that the depth of ocular components can change dramatically with anaesthesia. Researchers should therefore be wary of these concomitant effects and should employ adjustments to better render 'true' values.

Dopaminergic psychostimulants cause arousal from isoflurane-induced sedation without reversing memory impairment in rats.

BACKGROUND: Dopaminergic psychostimulants can restore arousal in anaesthetised animals, and dopaminergic signalling contributes to hippocampal-dependent memory formation. We tested the hypothesis that dopaminergic psychostimulants can antagonise the amnestic effects of isoflurane on visuospatial working memory. METHODS: Sixteen adult Sprague-Dawley rats were trained on a trial-unique nonmatching-to-location (TUNL) task which assessed the ability to identify a novel touchscreen location after a fixed delay. Once trained, the effects of low-dose isoflurane (0.3 vol%) on task performance and activity, assessed by infrared beam breaks, were assessed. We attempted to rescue deficits in performance and activity with a dopamine D1 receptor agonist (chloro-APB), a noradrenergic reuptake inhibitor (atomoxetine), and a mixed dopamine/norepinephrine releasing agent (dextroamphetamine). Anaesthetic induction, emergence, and recovery from anaesthesia were also investigated. RESULTS: Low-dose isoflurane impaired working memory in a sex-independent and intra-trial delay-independent manner as assessed by task performance, and caused an overall reduction in activity. Administration of chloro-APB, atomoxetine, or dextroamphetamine did not restore visuospatial working memory, but chloro-APB and dextroamphetamine recovered arousal to levels observed in the baseline awake state. Performance did not differ between induction and emergence. Animals recovered to baseline performance within 15 min of discontinuing isoflurane. CONCLUSIONS: Low-dose isoflurane impairs visuospatial working memory in a nondurable and delay-independent manner that potentially implicates non-hippocampal structures in isoflurane-induced memory deficits. Dopaminergic psychostimulants counteracted sedation but did not reverse memory impairments, suggesting that isoflurane-induced amnesia and isoflurane-induced sedation have distinct underlying mechanisms that can be antagonised independently.

Isoflurane-induced neuroinflammation and NKCC1/KCC2 dysregulation result in long-term cognitive disorder in neonatal mice.

BACKGROUND: The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+-K+-2Cl--1 (NKCC1) and K+-2Cl--2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. METHODS: We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified using ELISA. RESULTS: We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1ß levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1ß, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. CONCLUSIONS: Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Isoflurane preconditioning attenuates OGD/R-induced cardiomyocyte cytotoxicity by regulating the miR-210/BNIP3 axis.

Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R-induced upregulation of miR-210, a hypoxia-responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR-210 in regulating the effects of isoflurane preconditioning on OGD/R-induced cardiomyocyte injury, AC16 cells were transfected with anti-miR-210 or control anti-miRNA. Results showed that isoflurane preconditioning attenuated OGD/R-induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK-MB levels), which could be reversed by anti-miR-210. Isoflurane preconditioning also prevented OGD/R-induced increase in apoptotic rate, caspase-3 and caspase-9 activities, and Bax level and decrease in Bcl-2 expression level, while anti-miR-210 blocked these effects. We also found that anti-miR-210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R-induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p-DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR-210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR-210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R-induced cardiac cytotoxicity by regulating the miR-210/BNIP3 axis.

Research Progress of Hippocampal Dopamine System Changes in Perioperative Neurocognitive Disorders.

Perioperative neurocognitive disorders (PND) are a cognitive impairment that occurs after anesthesia, especially in elderly patients and significantly affects their quality of life. The hippocampus, as a critical region for cognitive function and an important location in PND research, has recently attracted increasing attention. However, in the hippocampus the impact of anesthesia and its underlying mechanisms remain unclear. This review focuses on investigation of the effects of anesthesia on the hippocampal dopamine (DA) system and explores its potential association with PND. Through comprehensive review of existing studies, it was found that anesthesia affects the hippocampus through various pathways involved in metabolism, synaptic plasticity and oxygenation. Anesthesia may also influence the DA neurotransmitter system in the brain which plays a role in emotions, rewards, learning and memory functions. Specifically, anesthesia may participate in the pathogenesis of PND by affecting the DA system within the hippocampus. Future studies should explore the molecular mechanisms of these effects through techniques such as neuroimaging to study real-time effects to improve animal models to better simulate clinical observations. For clinical application, it is recommended that physicians exercise caution when selecting and managing anesthetic drugs by adopting comprehensive cognitive assessment methods to reduce post-anesthesia cognitive risk. Overall, this review provides a better understanding of the relationship between the hippocampal DA system and perioperative neurocognitive function and provides valuable guidance for prevention and treatment strategies for PND.

The Impact of the Combined Effect of Inhalation Anesthetics and Iron Dextran on Rats' Systemic Toxicity.

Disruption of any stage of iron homeostasis, including uptake, utilization, efflux, and storage, can cause progressive damage to peripheral organs. The health hazards associated with occupational exposure to inhalation anesthetics (IA) in combination with chronic iron overload are not well documented. This study aimed to investigate changes in the concentration of essential metals in the peripheral organs of rats after iron overload in combination with IA. The aim was also to determine how iron overload in combination with IA affects tissue metal homeostasis, hepcidin-ferritin levels, and MMP levels according to physiological, functional, and tissue features. According to the obtained results, iron accumulation was most pronounced in the liver (19×), spleen (6.7×), lungs (3.1×), and kidneys (2.5×) compared to control. Iron accumulation is associated with elevated heavy metal levels and impaired essential metal concentrations due to oxidative stress (OS). Notably, the use of IA increases the iron overload toxicity, especially after Isoflurane exposure. The results show that the regulation of iron homeostasis is based on the interaction of hepcidin, ferritin, and other proteins regulated by inflammation, OS, free iron levels, erythropoiesis, and hypoxia. Long-term exposure to IA and iron leads to the development of numerous adaptation mechanisms in response to toxicity, OS, and inflammation. These adaptive mechanisms of iron regulation lead to the inhibition of MMP activity and reduction of oxidative stress, protecting the organism from possible damage.

Comparison of cardiopulmonary effects of propofol, ketamine-propofol and isoflurane anesthesia in the domestic chicken (Gallus gallus domesticus).

OBJECTIVE: To compare the effects of propofol, ketamine-propofol and isoflurane, at similar anesthetic depth, on cardiopulmonary variables in unpremedictated chickens. STUDY DESIGN: Prospective, randomized, crossover experimental trial. ANIMALS: A total of 10 male Leghorn domestic chickens, aged 3 months and body mass 1.4-2.0 kg. METHODS: Birds were randomly assigned to each of three anesthetic protocols, 7 days apart: intravenous propofol, intravenous ketamine-propofol or isoflurane. Anesthesia was induced (indicated by loss of righting reflex and tracheal intubation) and maintained with propofol (10 mg kg-1 minute-1, then 1.1 mg kg-1 minute-1), ketamine-propofol (5 mg mL-1 ketamine and 5 mg mL-1 propofol combined; 10 mg kg-1 minute-1, then 1.1 mg kg-1 minute-1) or isoflurane [5% vaporizer setting initially, then end-tidal concentration (Fe'Iso) of 2%] for 65 minutes. Anesthesia was maintained at a similar anesthetic depth based upon positive or negative responses to toe pinch. Heart rate (HR), respiratory rate (fR), noninvasive arterial blood pressure and arterial blood gases were measured during anesthesia. Propofol or ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to a noxious stimulus and recovery times were recorded. RESULTS: Anesthesia induction dose was 9.0 ± 0.8 (mean ± SD) and 12.2 ± 0.3 mg kg-1 for propofol and ketamine-propofol, respectively. Propofol and ketamine-propofol infusion rates and Fe'Iso required to prevent movement in response to the noxious stimulus were 0.88 ± 0.14 mg kg-1 minute-1, 0.92 ± 0.14 mg kg-1 minute-1 and 1.45 ± 0.28%, respectively. Cardiopulmonary variables remained clinically acceptable, but ketamine-propofol was associated with a significantly higher HR (p = 0.0001) and lower fR (p = 0.0001). Time to extubation did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Cardiovascular and respiratory variables were maintained within normal ranges in all treatments. Coadministration of ketamine with propofol significantly reduced the induction and maintenance dose of propofol.

Anaesthetic-sparing effect of the anxiolytic drug tasipimidine in Beagle dogs.

OBJECTIVE: To evaluate the effect of oral tasipimidine on dog handling, ease of catheter placement and propofol and isoflurane requirements for anaesthesia. STUDY DESIGN: Placebo-controlled, randomized, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 13.1 ± 2.7 kg with a mean age of 18.6 ± 1 months. METHODS: The dogs underwent four treatments before induction of anaesthesia with propofol. PP: placebo orally (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) intravenously (IV). TP: tasipimidine 30 µg kg-1 (PO) 60 minutes before induction of anaesthesia followed by placebo (NaCl 0.9%) IV. TMP: tasipimidine 30 µg kg-1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg-1 IV. TMPD: tasipimidine 30 µg kg-1 PO 60 minutes before induction of anaesthesia followed by methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by a dexmedetomidine constant rate infusion of 1 µg kg-1 hour-1. Sedation, response to catheter placement, intubation quality, time to loss of consciousness, time to intubation, required dose of propofol and minimum alveolar isoflurane concentration preventing motor movement (MACNM) were determined. A mixed-model analysis or the Friedman and Mann-Whitney test were used; p-value < 0.05. RESULTS: Response to catheter placement did not differ between treatments. Tasipimidine alone reduced the propofol dose by 30%. Addition of methadone or methadone and dexmedetomidine reduced the propofol dose by 48% and 50%, respectively. Isoflurane MACNM was reduced by 19% in tasipimidine-medicated dogs, whereas in combination with methadone or methadone and dexmedetomidine, isoflurane MACNM was reduced by 35%. CONCLUSIONS AND CLINICAL RELEVANCE: An anxiolytic dose of tasipimidine induced mild signs of sedation in dogs and reduced propofol and isoflurane requirements to induce and maintain anaesthesia, which needs to be considered in an anaesthetic plan.

The effect of oral pregabalin on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To investigate the effect of three different doses of oral pregabalin on minimum alveolar concentration of isoflurane (MACISO) in cats. STUDY DESIGN: Prospective, randomized, placebo-controlled, blinded, crossover trial. ANIMALS: A group of eight healthy adult cats aged 24-48 months. METHODS: Cats were randomly assigned to three oral doses of pregabalin (low dose: 2.5 mg kg-1, medium dose: 5 mg kg-1, high dose: 10 mg kg-1) or placebo 2 hours before MACISO determination, with the multiple treatments administered with a minimum 7 day washout period. Anesthesia was induced and maintained with isoflurane in oxygen until endotracheal intubation was achieved, and maintained with isoflurane with volume-controlled ventilation. MACISO was determined in triplicate using the bracketing technique and tail clamp method 120 minutes after pregabalin or placebo administration. Physiologic variables (including heart rate and blood pressure) recorded during MACISO determination were averaged and compared between the pregabalin and placebo treatments. One-way analysis of variance and the Friedman test were used to assess the difference for normally and non-normally distributed data, respectively. The Tukey test was used as a post hoc analysis. Values of p < 0.05 were considered significant. RESULTS: The MACISO with the medium- and high-dose pregabalin treatments were 1.33 ± 0.21% and 1.23 ± 0.17%, respectively. These were significantly lower than MACISO after placebo treatment (1.62 ± 0.13%; p = 0.014, p < 0.001, respectively), representing a decrease of 18 ± 9% and 24 ± 6%. The mean plasma pregabalin concentration was negatively correlated with MACISO values. Physiologic variables did not differ significantly between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Doses of 5 or 10 mg kg-1 pregabalin, administered orally 2 hours before determining MACISO, had a significant isoflurane-sparing effect in cats.

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs.

OBJECTIVE: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. STUDY DESIGN: Prospective, placebo-controlled, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. METHODS: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 µg kg-1 orally and placebo IV; TMP: tasipimidine 30 µg kg-1 orally and methadone 0.2 mg kg-1 IV; and TMPD: tasipimidine 30 µg kg-1 orally with methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by 1 µg kg-1 hour-1. Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. RESULTS: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

Isoflurane pretreatment protects against myocardial ischemia/reperfusion injury via mediating lncRNA CASC15/miR-542-3p axis.

The protective effect of isoflurane on cardiomyocyte ischemia/reperfusion injury (I/RI) was explored in hypoxia and reoxygenation (H/R) induced cardiomyocyte injury model. In terms of mechanism, the participation of long non-coding RNA CASC15/microR-542-3p axis was further discussed. H9c2 cells received H/R treatment to mimic myocardial I/RI. RT-qPCR was performed to quantify mRNA levels. Cell viability and apoptosis were evaluated after isoflurane pretreatment and cell transfection. ELISA was performed to measure the concentrations of inflammatory/oxidative stress-related cytokines (TNF-α, IL-6, MDA, SOD). The target relationship between CASC12 and miR-542-3p was determined via dual-luciferase reporter assay. Isoflurane pretreatment alleviated H/R-induced cell viability suppression and cell apoptosis promotion, which was accompanied by CASC15 downregulation. CASC15 overexpression abolished the influence of isoflurane on cardiomyocytes' viability and apoptosis. H/R-induced excessive release of TNF-α and IL-6 was hold down by isoflurane, which was re-activated after CASC15 overexpression. The concentration changes of both MDA and SOD by isoflurane were reversed by CASC15 overexpression. CASC15 functioned as miR-542-3p sponger, and miR-542-3p overexpression attenuated the effect of isoflurane and CASC15 on H/R-induced cardiac I/RI. Isoflurane pretreatment was beneficial for the alleviation of cardiac I/RI by inhibiting oxidative stress and myocardial inflammatory response. CASC15/miR-542-3p axis was required for isoflurane to exhibit its protective activity against cardiac I/RI.

Anesthesia and humane euthanasia methods for king worm larvae (Zophobas morio).

A growing spotlight on insect welfare as research subjects, fodder for vertebrate animals, and patients for veterinarians highlights the need to establish humane euthanasia methods for these species. An insect of increasing commercial importance is the king worm (Zophobas morio), a type of darkling beetle larvae. The initial objective of this study was to determine if prolonged exposure to isoflurane would lengthen anesthetic recovery and lead to euthanasia. Larvae were exposed to isoflurane for 10 min, 40 min, 70 min, 190 min, 13 h, and 24 h (n = 10 for each treatment duration group), and time to recovery was subsequently monitored in room air. The second objective was to determine effectiveness of secondary euthanasia methods: injectable potassium chloride at 1 mg/g body weight (n = 5) and 3 mg/g body weight (n = 5) doses; immersion in 200 proof ethanol (n = 10), 10% buffered formalin (n = 10), and water (n = 10); and freezing at -18°C (n = 10). Prolonged exposure to isoflurane led to extended recovery times, but 100% mortality was not achieved. Submersion in ethanol and injection of potassium chloride at a 3 mg/g body weight dose resulted in 100% mortality. If these larvae are to be used as future food sources, a humane euthanasia method that preserves the ability to be consumed is required.

Effects of ketamine, propofol and isoflurane on electrocardiographic variables in clinically healthy dogs premedicated with medetomidine and midazolam.

The purpose of this study was to investigate the effects of three anesthetic agents, with premedication of medetomidine and midazolam, on electrocardiographic variables in dogs. Ten adult mixed breed dogs were used in a crossover design study, where they received ketamine, propofol and isoflurane treatments with a one-week washout period between them. In all three groups, medetomidine was administered first followed by midazolam after 15 min. Then, after 20 min, group 1 received ketamine intravenously (IV), group 2 received propofol (IV), and group 3 received isoflurane (inhalation). In all dogs, electrocardiographs were taken before and after premedication's, as well as every 15 min during anesthesia. Medetomidine significantly decreased heart rate and P wave amplitude and increased PR interval, R wave amplitude, QT interval, and T wave amplitude. Midazolam increased the amplitude of the R and T waves. Ketamine increased the heart rate and PR interval. Propofol increased the heart rate for up to 15 min, decreased the PR interval for up to 30 min, and the QT interval for up to 45 min. Isoflurane increased the heart rate and decreased the amplitude of R and T waves. The results showed that the drugs used in this study did not have many side effects on electrocardiographic variables and could be used without serious concern. The most important side effects observed were a severe reduction in heart rate and 1st degree atrioventricular (AV) block and, to a lesser extent, 2nd degree AV block caused by medetomidine and midazolam which were masked by the anesthetics.

Dysregulation of iron homeostasis and ferroptosis in sevoflurane and isoflurane associated perioperative neurocognitive disorders.

In recent years, sevoflurane and isoflurane are the most popular anesthetics in general anesthesia for their safe, rapid onset, and well tolerant. Nevertheless, many studies reported their neurotoxicity among pediatric and aged populations. This effect is usually manifested as cognitive impairment such as perioperative neurocognitive disorders. The wide application of sevoflurane and isoflurane during general anesthesia makes their safety a major health concern. Evidence indicates that iron dyshomeostasis and ferroptosis may establish a role in neurotoxicity of sevoflurane and isoflurane. However, the mechanisms of sevoflurane- and isoflurane-induced neuronal injury were not fully understood, which poses a barrier to the treatment of its neurotoxicity. We, therefore, reviewed the current knowledge on mechanisms of iron dyshomeostasis and ferroptosis and aimed to promote a better understanding of their roles in sevoflurane- and isoflurane-induced neurotoxicity.

Intraoperative Isoflurane End-Tidal Concentration during Infusion of Fentanyl, Tramadol, or Fentanyl-Tramadol Combination in Cats.

The aim of this study was to evaluate the end-tidal concentration of isoflurane required, clinical parameters, intraoperative antinociceptive effect, and postoperative analgesia in cats undergoing ovariohysterectomy, receiving fentanyl, tramadol, or fentanyl/tramadol. Sixty-six cats in three groups, were premedicated with dexmedetomidine and infused with one of the following treatments: fentanyl, tramadol, or fentanyl/tramadol combination. Anesthesia was induced with alfaxolone and maintained with isoflurane, titrated to keep heart rate, respiratory rate and systolic arterial pressure within target values recorded at endotracheal intubation. An intraoperative cumulative scale was performed. Postoperatively, a short form of the Glasgow Composite Measure Pain Scale Feline was used at 2, 12, and 24 h. The groups were similar for age, weight, dose of dexmedetomidine, and alfaxalone administered. A greater reduction in the end-tidal isoflurane fraction was observed with the combined fentanyl/tramadol infusion than with either fentanyl or tramadol alone. No differences in the end-tidal isoflurane fraction were found between fentanyl or tramadol alone. Hemodynamic stability associated with minimal cardiopulmonary changes, low response to noxious intraoperative stimulation, and low postoperative pain scores were also observed with the fentanyl/tramadol combination. The fentanyl/tramadol combination provided a reduction in the end-tidal isoflurane fraction compared with fentanyl or tramadol alone.

Isoflurane treatment for refractory and super-refractory status epilepticus in dogs.

Introduction: Resistant epileptic episodes, such as refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE), are neurological emergencies that require immediate medical treatment. Although inhalational anesthetics, such as isoflurane (ISO), have been proposed as a means of seizure control in dogs, there is currently a lack of both experimental and clinical studies on this subject. Study design: This is a retrospective clinical study. Methods: Records of dogs that received ISO for the management of RSE and SRSE during their intensive care unit (ICU) hospitalization at the Companion Animal Clinic of the Aristotle University of Thessaloniki were included in the present study. The study period spanned from February 2013 to March 2023. Dogs were identified as responders (R) when RSE/SRSE ceased after ISO administration, and the dogs were successfully discharged from the ICU after ISO discontinuation. Dogs were identified as non-responders (NR) when RSE/SRSE ceased after ISO administration, but RSE/SRSE reoccurred after ISO discontinuation. Additional data about the number and time of ISO cycles, the time of ICU hospitalization, the side effects of ISO administration, and an additional administration of antiepileptic drugs (AEDs) and anesthetic drugs were also recorded. Results: A total of 20 dogs with 26 recorded RSE/SRSE episodes and 26 anesthetic cycles with ISO were included in the present study. The clinical termination of seizure activity was achieved 100% (26/26) in all episodes. In 73.1% (19/26) of the episodes, ISO administration resulted in successful RSE/SRSE treatment. Poor outcome was recorded in 26.9% (7/26) of the episodes because RSE/SRSE reoccurred after ISO discontinuation, and the dogs were euthanatized or died due to cardiac arrest. Inspiratory ISO ranged between 0.5 and 4.0%. The median time of the anesthetic cycles with ISO was 12.67 h (4.00-62.00). The median duration of the ICU hospitalization was 48.00 h (24.00-120.00). At least one ISO-related side effect was recorded in 23 out of 26 (88.5%) episodes. Conclusion: To the authors' knowledge, this is the first clinical study that addresses the administration of ISO for RSE/SRSE treatment in dogs. The use of ISO may be beneficial in terminating RSE/SRSE; however, further prospective studies are necessary to confirm this observation.