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Background: Sclareol (SCL), a labdane diterpene compound found in Salvia sclarea L., exhibited therapeutic effects. This study investigated the potential interaction between SCL and diazepam (DZP) in modulating sedation in the thiopental sodium-induced sleeping animal model, supported by in-silico molecular docking analysis., Methods: The control, sclareol (5, 10 and 20 mg/kg), and the reference drugs [diazepam: 3 mg/kg and Caffeine (CAF): 10 mg/kg] were used in male albino mice. Then, sodium thiopental (40 mg/kg, i.p.) was administrated to induce sleep. The latent period, percentage of sleep incidence and modulation of latency were measured. Further, homology modeling of human γ-aminobutyric acid (GABA) was conducted examine the binding mode of GABA interaction with SCL, DZP, and CAF compounds RESULTS: SCL (low dose) slightly increased the sleep latency, while the higher dose significantly prolonged sleep latency. DZP, a GABA A receptor agonist, exhibited strong sleep-inducing properties, reducing sleep latency, and increasing sleeping time. Caffeine (CAF) administration prolonged sleep latency and reduced sleeping time, consistent with its stimulant effects. The combination treatments involving SCL, DZP, and CAF showed mixed effects on sleep parameters. The molecular docking revealed good binding affinities of SCL, DZP, and CAF for GABA A receptor subunits A2 and A5., Conclusions: Our findings highlighted the complex interplay between SCL, DZP, and CAF in regulating sleep behaviors and provided insights into potential combination therapies for sleep disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked. In the FST test, the animals were subjected to forced swimming after 30 min of administration of the test and/or controls for 5 min. In this case, immobility time was measured. In silico studies were conducted to evaluate the involvement of GABA receptors. SCL (5 and 10 mg/kg) significantly increased the latency and decreased sleeping time compared to the control in the TS-induced sleeping time study. DZP (3 mg/kg) showed a sedative-like effect in animals in both sleeping and FST studies. QR (50 mg/kg) exhibited a similar pattern of activity as SCL. However, its effects were more prominent than those of SCL groups. SCL (10 mg/kg) altered the DZP-3-mediated effects. SCL-10 co-treated with QR-50 significantly (p < 0.05) increased the latency and decreased sleep time and immobility time, suggesting possible synergistic antidepressant-like effects. In silico studies revealed that SCL and QR demonstrated better binding affinities with GABAA receptor, especially α 2 , α 3 , and α 5 subunits. Both compounds also exhibited good ADMET and drug-like properties. In animal studies, the both compounds worked synergistically to provide antidepressant-like effects in a slightly different fashion. As a conclusion, the combined administration of SCL and QR may be used in upcoming neurological clinical trials, according to in vivo and in silico findings. However, additional investigation is necessary to verify this behavior and clarify the potential mechanism of action., (© 2024 John Wiley & Sons Ltd.)

Background: Thiopental has been used as a pharmacological cerebral protection strategy during carotid endarterectomy surgeries. However, the optimal dosage required to induce burst suppression on the electroencephalogram (EEG) remains unknown. This retrospective study aimed to determine the optimal dosage of thiopental required to induce burst suppression during non-shunt carotid endarterectomy., Methods: The Neurological Institute of Thailand Review Board approved the study. Data were collected from 2009 to 2019 for all non-shunt carotid endarterectomy patients who received thiopental for pharmacological cerebral protection and had intraoperative EEG monitoring. Demographic information, carotid stenosis severity, intraoperative EEG parameters, thiopental dosage, carotid clamp time, intraoperative events, and patient outcomes were abstracted., Results: The study included 57 patients. Among them, 24 patients (42%) achieved EEG burst suppression pattern with a thiopental dosage of 26.3±10.1 mg/kg/hr. There were no significant differences in perioperative events between patients who achieved burst suppression and those who did not. After surgery, 33.3% of patients who achieved burst suppression were extubated and awakened. One patient in the non-burst suppression group experienced mild neurological deficits. No deaths occurred within one month postoperative., Conclusions: The optimal dosage of thiopental required to achieve burst suppression on intraoperative EEG during non-shunt carotid endarterectomy was 26.3±10.1 mg/kg/hr., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Sookplung P et al.)

Thiopental sodium (TPTS) is a barbiturate general anesthetic, while its effects on hypoxia/reoxygenation (H/R)-induced injury are still unclear. This study aimed to investigate whether TPTS exerts protective effects against the H/R-induced osteoblast cell injury and explore the underlying mechanisms. Osteoblast cell injury model was induced by the H/R condition, which was treated with or without TPTS. Cell viability and lactate dehydrogenase (LDH) release were determined by the corresponding commercial kits. The levels of oxidative stress were determined in the experimental groups. Cell apoptosis and Caspase-3 activities were determined by propidium iodide staining and substrate-based assay, respectively. Western blotting and qRT-PCR were performed to measure the mRNA and protein levels, respectively. Treatment with TPTS was able to increase cell viability and reduce LDH release in H/R-induced osteoblasts. Additionally, TPTS regulated oxidative stress in H/R-induced osteoblasts by suppressing malondialdehyde (MDA) and reactive oxygen species (ROS) as well as boosting superoxide dismutase (SOD). TPTS was able to suppress cell apoptosis by suppressing Caspase-3 activity and cleavage. TPTS exerted protective effects against cell injury and apoptosis induced by the H/R conditions, which were associated with its regulation of Akt signaling. Moreover, TPTS induced osteoblast differentiation under the H/R condition. In summary, TPTS attenuates H/R-induced injury in osteoblasts by regulating AKT signaling., (© 2023. The Society for In Vitro Biology.)

Background: Propofol and thiopental are commonly used induction agents in neonatal anesthesia. Even though both hypnotics have been used off-label for many years, pharmacological knowledge regarding these agents is scarce in neonates. The significant variability in neonates' body composition, organ function, and maturation makes pharmacological studies highly relevant albeit challenging. As a result, there is currently limited data about the anesthetic induction dose of thiopental and propofol in neonates. In addition, a knowledge gap exists concerning the pharmacodynamics of induction doses., Objective: To determine the median effective anesthetic induction dose of propofol and thiopental in neonatal patients of different gestational and postnatal ages and evaluate the pharmacodynamics of the anesthesia induction doses on the neonatal systemic and cerebral hemodynamics., Methods: This is a single-center, prospective, open-label, interventional, dose-finding study, including neonatal patients from birth up to 28 postnatal days undergoing general anesthesia for surgical or diagnostic procedures. The patients will be stratified according to their gestational and postnatal age and allocated to one of the two trial arms: anesthesia induction with propofol or anesthesia induction with thiopental. We will use Dixon's up-and-down method to estimate the median effective anesthesia induction dose of both agents in neonates of different gestational and postnatal ages. In addition, we will study the relationship between anesthesia induction doses and changes in systemic and cerebral hemodynamics., Discussion: Alterations in the systemic and cerebral regional hemodynamics secondary to anesthesia induction may be harmful in neonates, especially premature and critically ill newborns, due to their immature organ systems, reduced physiological reserves, and impaired cerebral autoregulation. Perfusion homeostasis is considered one of the significant and modifiable determinants of anesthesia-related neurocognitive outcomes. Therefore, dose-finding and safety pharmacological studies of the anesthetic induction agents in neonates are urgently needed and acknowledged as a high priority by the European Medicine Agency. Estimating adequate induction doses to ensure optimal depth of anesthesia while avoiding systemic and cerebral hemodynamic disturbances will help ensure safe anesthesia and potentially improve anesthesia-related outcomes in this group of patients., Trial Registration: EudraCT (EudraCT Identifier: 2019-001534-34), 05.07.2022., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Aims: To compare the effect on mortality and length of hospital stay of propofol with that of sodium thiopentone for the management of dogs with status epilepticus (SE) and refractory status epilepticus (RSE)., Methods: In this cohort study, medical records of a veterinary referral clinic in Argentina were retrospectively searched for dogs that were hospitalised and required induction of therapeutic coma (TC) with either propofol or sodium thiopentone for the management of SE or RSE of any cause. A logistic regression model was performed to evaluate the association between the type of anaesthetic used and in-hospital mortality adjusting for the type of epilepsy (idiopathic, structural, or reactive). Kaplan-Meier estimated survival curves for the length of hospital stay by the type of anaesthetic drug were compared using the log-rank test (deaths were considered censored events). Cox proportional hazards regression was used to estimate hazard ratios for time to hospital discharge, unadjusted and adjusted for type of epilepsy., Results: A total of 24 dogs with SE were included in the study: eight treated with propofol and 16 treated with sodium thiopentone. Four dogs treated with propofol (proportion = 0.50; 95% CI = 0.15-0.84), and eight treated with sodium thiopentone (proportion = 0.50; 95% CI = 0.50-0.74) died during hospitalisation. The median hospitalisation time was 43 (IQR 24-56) hours for dogs that were treated with propofol and 72 (IQR 64-96) hours for dogs that were treated with sodium thiopentone. There was no evidence of a difference in the median duration of TC in dogs treated with propofol (12 (IQR 8-24) hours) or with sodium thiopentone (12 (IQR 7.5-20) hours; p = 0.946). In the logistic regression model, no evidence of association between the anaesthetic protocol for the management of RSE and in-hospital mortality, adjusted for the type of epilepsy, was found (OR 1.09 (95% CI = 0.17-6.87); p = 0.925). Cox regression analysis revealed a difference in the time to hospital discharge, adjusted by the type of epilepsy, between treatment groups (HR = 0.05 (95% CI = 0.01-0.54); p = 0.013)., Conclusions and Clinical Relevance: The time spent in hospital before discharge was longer in dogs with RSE treated with sodium thiopentone compared to those treated with propofol. However, as the sample size was very small, the results obtained in the present study should be analysed with caution. Further studies including a greater number of dogs are required.

Introduction: One of the most important factors influencing post-transplant success in kidney transplantation is preserving the viability of the organ from removal to transfer into the recipient., Aim: This study aimed to reduce the energy requirement with thiopental doses administered before organ transplantation, and to increase the organ viability by minimizing the tissue damage during the cold ischemia process., Materials and Methods: Twenty female Wistar albino rats were divided into two groups: control group (group C), and thiopental group (group T). In group C, a midline incision was performed, and the renal artery was isolated under ketamine and xylazine anesthesia. A standard organ storage solution (cooled to +4°C) was used for kidney perfusion. Nephrectomy was applied, and the removed kidneys were placed into +4°C standard organ storage solution and stored at +4°C for 12 hours. Animals in group T were subjected to the procedures explained above under 85 mg/kg thiopental sodium anesthesia. After 12-hour storage, samples from the kidney tissues were fixed in 10% neutral buffered formalin. Histopathological evaluation and apoptosis detection via TUNEL method were performed., Results: Tubular necrosis was more extensive in group C compared with that in group T and this difference was statistically significant. Similarly, vacuolization was widely observed in group C, and this increase was also statistically significant. For the 'dilatation of Bowman's space' parameter, a significant decrease was observed in group T compared with group C. When the apoptotic index values of both groups were examined, it was seen that they were lower in group T than those in group C. This result was statistically significant., Conclusions: These data suggest that thiopental provides protection to the kidney tissue during the cold storage process. Thiopental has been shown to decrease the number of apoptotic cells in the kidney tissue when administered to the donor before organ transplantation, increasing the organ viability., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To determine the normal optical nerve sheath (ONS) diameter ultrasonography (ONSUS) and evaluate the possible effects of drugs on ONS diameter during anesthetic induction in healthy pigs., Methods: Healthy piglets were divided into three groups: a control group, that received xylazine and ketamine (X/K); other that received xylazine, ketamine and propofol (X/K/P); and a third group that received xylazine, ketamine, and thiopental (X/K/T). The sheath diameter was assessed by ultrasonography calculating the average of three measurements of each eye from the left and right sides., Results: 118 animals were anesthetized (49 X/K 33 X/K/P and 39 X/K/T). Mean ONS sizes on both sides in each group were 0.394 ± 0.048 (X/K), 0.407 ± 0.029 (X/K/P) and 0.378 ± 0.042 cm (X/K/T) (medians of 0.400, 0.405 and 0.389, respectively). The ONS diameter varied from 0.287-0.512 cm (mean of 0.302 ± 0.039 cm). For group X/K, the mean diameter was 0.394 ± 0.048 cm. Significant differences in ONS sizes between the groups P and T (X/K/P > X/K/T, p = 0.003) were found. No statistically significant differences were detected when other groups were compared (X/K = X/K/P, p = 0.302; X/K = X/K/T, p = 0.294)., Conclusions: Sedation with thiopental lead to significative ONS diameter reduction in comparison with propofol. ONSUS may be useful to evaluate responses to thiopental administration.

The current study aimed to investigate the neuropharmacological properties of ethanol, acetone, and ethyl acetate leaf extracts of Chassalia curviflora ( C. curviflora ) in mouse models. The neuropharmacological properties of this plant were studied on Swiss albino mice at dosages of 50, 100, and 200 mg/kg body weight in thiopental sodium-induced sleeping time test, and at dosages of 100 and 200 mg/kg body weight in other tests. The extracts caused a marked reduction in the initiation and sleep length ( P <0.05) in studies on thiopental sodium-induced sleeping time at dosages of 100 and 200 mg/kg and a significant decrease ( P <0.05) was found in terms of unconstrained locomotor and explorative activities in both hole crossing and open field tests at dosages of 100 and 200 mg/kg. Furthermore, the extracts increased sleeping time with a dosage-dependent onset of action. The hole-board test extracts also reduced the number of head dips at dosages of 100 and 200 mg/kg ( P <0.05). It was found in this study that C. curviflora had the best neuropharmacological properties at a dosage of 200 ml/kg. Our findings also showed that all of the extracts from C. curviflora were experimentally active in an in vivo model. The study results suggested that the leaves had strong anti-depressant and hypnotic CNS properties that might be exploited for neuropharmacological adjuvant therapy in conventional medicine. However, pharmacological studies are warranted to explore the active substances and the mode of action., Competing Interests: The authors declare that they have no conflict of interest.

Background: In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine., Objectives: To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats., Material and Methods: Male albino Wistar type rats received intraperitoneally (ip.) 30 mg/kg ketamine in the ketamine alone (KG) group (n = 6), 15 mg/kg thiopental in the thiopental alone (TG) group (n = 6), and 30 mg/kg ketamine + 15 mg/kg thiopental in the ketamine+thiopental (KTG) group (n = 6). The same volume of distilled water as solvent was given to the healthy (HG) animal group. This procedure was repeated once daily for 30 days. At the end of this period, the animals were killed by decapitation and their livers were removed. In liver tissue, malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) levels were measured. The IL-1β, IL-6, TNF-α, adrenalin (ADR), noradrenalin (NDR), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined in blood samples taken from the tail veins., Results: In the group treated with ketamine and thiopental alone, MDA, TOS, IL-1β, IL-6, TNF-α, ADR, NDR, ALT, and AST levels were found to be high, and those of tGSH and TAS to be low. However, there was no significant change in the levels of these parameters in the KTG., Conclusions: These results indicate that oxidative stress and inflammation developed in the liver tissue of the group that used ketamine and thiopental alone, suggesting that the KT form may be safer in terms of toxicity in the clinical usage.

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Aim: To investigate the effects of midazolam (MDZ) and thiopental on neonatal and adult rat brains., Material and Methods: The study included adult and 7-day-old rats that were administered 9 mg/kg of MDZ, 60 mg/kg of thiopental, or both. The Bax, procaspase-3, and caspase-3 levels were assessed using Western Blot analysis and the total oxidative stress index (OSI) values were measured spectrophotometrically., Results: The procaspase-3 and caspase-3 levels were 12% and 6% lower in the neonatal MDZ group when compared to the control group. The Bax, procaspase-3, and caspase-3 levels were higher in the neonatal thiopental group by 25%, 4%, and 34%, and in the MDZ group by 16%, 19%, and 43% when compared to the neonatal control group. In the adult rats, the caspase-3 levels were 10 times higher in the MDZ group when compared to the control and thiopental groups. Moreover, the caspase-3 levels were 7 times higher in the adult thiopental group when compared to the control group. The OSI values in the neonatal rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05). Similarly, the OSI values in the adult rats were significantly higher in the neonatal MDZ and neonatal thiopental groups when compared to the control group (p < 0.05)., Conclusion: MDZ and thiopental may promote apoptosis and oxidative stress, and thereby result in neurotoxicity, with MDZ showing a greater effect in adults and thiopental showing a greater effect in neonates.

Background: Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants., Methods: In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test., Results: Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test., Conclusion: 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section., Trial Registration: IRCT No: 2016082819470 N45 , 13/03/2019., (© 2021. The Author(s).)

Activation of renal sensory nerves by chemo- and mechanosensitive stimuli produces changes in efferent sympathetic nerve activity (SNA) and arterial blood pressure (ABP). Anesthesia and sex influence autonomic function and cardiovascular hemodynamics, but it is unclear to what extent anesthesia and sex impact SNA and ABP responses to renal sensory stimuli. We measured renal, splanchnic, and lumbar SNA and ABP in male and female Sprague-Dawley rats during contralateral renal infusion of capsaicin and bradykinin or during elevation in renal pelvic pressure. Responses were evaluated with a decerebrate preparation or Inactin, urethane, or isoflurane anesthesia. Intrarenal arterial infusion of capsaicin (0.1-30.0 μM) increased renal SNA, splanchnic SNA, or ABP but decreased lumbar SNA in the Inactin group. Intrarenal arterial infusion of bradykinin (0.1-30.0 μM) increased renal SNA, splanchnic SNA, and ABP but decreased lumbar SNA in the Inactin group. Elevated renal pelvic pressure (0-20 mmHg, 30 s) significantly increased renal SNA and splanchnic SNA but not lumbar SNA in the Inactin group. In marked contrast, SNA and ABP responses to every renal stimulus were severely blunted in the urethane and decerebrate groups and absent in the isoflurane group. In the Inactin group, the magnitude of SNA responses to chemo- and mechanosensory stimuli were not different between male and female rats. Thus, chemo- and mechanosensitive stimuli produce differential changes in renal, splanchnic, and lumbar SNA. Experimentally, future investigations should consider Inactin anesthesia to examine sympathetic and hemodynamic responses to renal sensory stimuli. NEW & NOTEWORTHY The findings highlight the impact of anesthesia, and to a lesser extent sex, on sympathetic efferent and hemodynamic responses to chemosensory and mechanosensory renal stimuli. Sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses were present in Inactin-anesthetized rats but largely absent in decerebrate, isoflurane, or urethane preparations. Renal chemosensory stimuli differentially changed SNA: renal and splanchnic SNA increased, but lumbar SNA decreased. Future investigations should consider Inactin anesthesia to study SNA and hemodynamic responses to renal sensory nerve activation.

Elevated renal afferent nerve (ARNA) activity or dysfunctional reno-renal reflexes via altered ARNA sensitivity contribute to hypertension and chronic kidney disease. These nerves contain mechano- and chemosensitive fibers that respond to ischemia, changes in intrarenal pressures, and chemokines. Most studies have utilized various anesthetized preparations and exclusively male animals to characterize ARNA responses. Therefore, this study assessed the impact of anesthesia, sex, and circadian period on ARNA responses and sensitivity. Multifiber ARNA recordings were performed in male and female Sprague-Dawley rats (250-400 g) and compared across decerebrate versus Inactin, isoflurane, and urethane anesthesia groups. Intrarenal artery infusion of capsaicin (0.1-50.0 μM, 0.05 mL) produced concentration-dependent increases in ARNA; however, the ARNA sensitivity was significantly greater in decerebrate versus Inactin, isoflurane, and urethane groups. Increases in renal pelvic pressure (0-30 mmHg, 30 s) produced pressure-dependent increases in ARNA; however, ARNA sensitivity was again greater in decerebrate and Inactin groups versus isoflurane and urethane. Acute renal artery occlusion (30 s) increased ARNA, but responses did not differ across groups. Analysis of ARNA responses to increased pelvic pressure between male and female rats revealed significant sex differences only in isoflurane and urethane groups. ARNA responses to intrarenal capsaicin infusion were significantly blunted at nighttime versus daytime; however, ARNA responses to increased pelvic pressure or renal artery occlusion were not different between daytime and nighttime. These results demonstrate that ARNA sensitivity is greatest in decerebrate and Inactin-anesthetized groups but was not consistently influenced by sex. NEW & NOTEWORTHY We determined the impact of anesthesia, sex, and circadian cycle on renal afferent nerve (ARNA) sensitivity to chemical and mechanical stimuli. ARNA sensitivity to renal capsaicin infusion was greatest in decerebrate > Inactin > urethane or isoflurane groups. Elevated renal pelvic pressure significantly increased ARNA; decerebrate and Inactin groups exhibited the greatest ARNA sensitivity. Sex differences in renal afferent responses were not consistently observed. Circadian cycle altered chemosensory but not mechanosensory responses.

This work evaluates solid lipid nanoparticles of thiopental sodium against obesity-induced cardiac dysfunction and hypertrophy and explores the possible mechanism of action. TS loaded SLNs were formulated by hot-homogenization and solvent diffusion method. TS-SLNs were scrutinized for entrapment efficiency, drug loading capacity, gastric stability, particle size, in vitro drug release. Mice were feed with the normal chow or high-fat diet for 08 weeks to induce obesity and primary cardiomyocytes. The therapeutic effects of thiopental sodium in the high fat diet (HFD) induced cardiac hypertrophy. Systolic blood pressure (SBP) was estimated at a regular time interval. At the end of the experimental study, systolic pressure left ventricular, LV end-diastolic pressure and rate of increase of LV pressure and antioxidant, apoptosis, cytokines and inflammatory scrutinized. HFD induced group mice exhibited a reduction in the body weight and enhancement of cardiac hypertrophy marker and dose-dependent treatment of thiopental sodium up-regulation the body weight and down-regulated the cardiac hypertrophy. Thiopental sodium significantly ( p  < .001) dose-dependently altered the antioxidant, biochemical, cardiac parameters and remodeling. Thiopental sodium significantly ( p  < .001) dose-dependently reduced the SBP. Thiopental sodium altered the apoptosis marker, pro-inflammatory cytokines, inflammatory parameters along with reduced the p38-MAPK level. The cardiac protective effect of thiopental sodium shed light on future therapeutic interventions in obesity and related cardiovascular complications via inflammatory pathway.

The effects of anaesthetic agents on brain energy metabolism may explain their shared neurophysiological actions but remain poorly understood. The brain lactate shuttle hypothesis proposes that lactate, provided by astrocytes, is an important neuronal energy substrate. Here we tested the hypothesis that anaesthetic agents impair the brain lactate shuttle by interfering with astrocytic glycolysis. Lactate biosensors were used to record changes in lactate release by adult rat brainstem and cortical slices in response to thiopental, propofol and etomidate. Changes in cytosolic nicotinamide adenine dinucleotide reduced (NADH) and oxidized (NAD + ) ratio as a measure of glycolytic rate were recorded in cultured astrocytes. It was found that in brainstem slices thiopental, propofol and etomidate reduced lactate release by 7.4 ± 3.6% (P < 0.001), 9.7 ± 6.6% (P < 0.001) and 8.0 ± 7.8% (P = 0.04), respectively. In cortical slices, thiopental reduced lactate release by 8.2 ± 5.6% (P = 0.002) and propofol by 6.0 ± 4.5% (P = 0.009). Lactate release in cortical slices measured during the light phase (period of sleep/low activity) was ~25% lower than that measured during the dark phase (period of wakefulness) (326 ± 83 μM vs 430 ± 118 μM, n = 10; P = 0.04). Thiopental and etomidate induced proportionally similar decreases in cytosolic [NADH]:[NAD + ] ratio in astrocytes, indicative of a reduction in glycolytic rate. These data suggest that anaesthetic agents inhibit astrocytic glycolysis and reduce the level of extracellular lactate in the brain. Similar reductions in brain lactate release occur during natural state of sleep, suggesting that general anaesthesia may recapitulate some of the effects of sleep on brain energy metabolism., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity., Competing Interests: The authors have declared that no competing interests exist. Micromem is not a commercial source, but the name of the project that is financed by the French National Agency for Research.

Inhibitors of acetylcholinesterase (AChE), which have an important role in the prevention of excessive AChE activity and β-amyloid (Aβ) formation are widely used in the symptomatic treatment of Alzheimer's disease (AD). The inhibitory effect of anesthetic agents on AChE was determined by several approaches, including binding mechanisms, molecular docking and kinetic analysis. Inhibitory effect of intravenous anesthetics on AChE as in vitro and in vivo have been discovered. The midazolam, propofol and thiopental have shown competitive inhibition type (midazolam > propofol > thiopental) and Ki values were found to be 3.96.0 ± 0.1, 5.75 ± 0.12 and 29.65 ± 2.04 µM, respectively. The thiopental and midazolam showed inhibition effect on AChE in vitro, whereas they showed activation effect in vivo when they are combined together. The order of binding of the drugs to the active site of the 4M0E receptor was found to be midazolam > propofol > thiopental. This study on anesthetic agents that are now widely used in surgical applications, have provided a molecular basis for investigating the drug-enzyme interactions mechanism. In addition, the study is important in understanding the molecular mechanism of inhibitors that are effective in the treatment of AD.

Objective: Although regional anesthesia is the most frequently used method for selected surgical approaches, general anesthesia (GA) is still common. Awareness and recall of events are among the main hazards during GA, particularly in Caesarean Section (C/S). In this study, we decided to compare depth of anesthesia, that was measured by Bispectral index (BIS) and isolated forearm technique (IFT) in GA, induced by propofol vs. thiopental for elective C/S. We also aimed to determine the incidence of postoperative recall using these two anesthetic medications., Methods: Ninety parturient were allocated to receive either thiopental (group T) or propofol (group P) with blocking on a 1:1 ratio. All patients underwent standard GA. BIS and IFT were used to monitor depth of anesthesia at different predetermined perioperative events. All patients were evaluated for recall of the events., Results: No patient recalled the perioperative events during the follow up period. BIS scores were significantly lower in group P compared with group T after induction of GA until discontinuation of volatile anesthetics (p < 0.001). IFT values were signifi cantly higher in thiopental group in time interval of induction to skin incision comparing to propofol group (p < 0.050)., Conclusion: The current study suggests regarding better effect of propofol on decreasing of awareness during anesthesia and surgery, it seems to be better to use propofol in cases where we are forced to use GA in cesarean section.

Previous studies indicated that some general anesthetics induce long-term antidepressant and/or anxiolytic-like effects. This raises the concern about the use of anesthesia in surgeries that precede psychopharmacological tests, since it may be a potential bias on results depending on the experimental design used. Thus, we evaluated whether general anesthetics used in surgeries preceding psychopharmacological tests would affect rats behavior in tests predictive of antidepressant or anxiolytic-like effects. We tested if a single exposure to sub-anesthetic or anesthetic doses of tribromoethanol, chloral hydrate, thiopental or isoflurane would change rats behavior in the forced swimming test (FST) or in the elevated plus-maze (EPM) test, at 2 h or 7 days after their administration. We also evaluated whether prior anesthesia would interfere in the detection of the antidepressant-like effect of imipramine or the anxiolytic-like effect of diazepam. Previous anesthesia with the aforementioned anesthetics did not change rats behaviors in FST per se nor it changed the antidepressant-like effect induced by imipramine treatment. Rats previously anesthetized with tribromoethanol or chloral hydrate exhibited, respectively, anxiogenic-like and anxiolytic-like behaviors in the EPM. Prior anesthesia with thiopental or isoflurane did not produce any per se effect in rats behaviors in the EPM nor disturbed the anxiolytic-like effect of diazepam. Our results suggest that, in our experimental conditions, tribromoethanol and chloral hydrate are improper anesthetics for surgeries that precede behavioral analysis in the EPM. Isoflurane or thiopental may be suitable for anesthesia before evaluation in the EPM or in the FST., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To compare the effect of chemical and mechanical stimulation on arytenoid cartilage motion during anaesthetic induction with alfaxalone, thiopentone or propofol., Study Design: Masked, randomized, crossover study., Animals: A group of eight adult Beagle dogs., Methods: Anaesthesia was induced with thiopentone (7.5 mg kg -1 ), propofol (3 mg kg -1 ) or alfaxalone (1.5 mg kg -1 ) intravenously (IV), which were concurrently paired with either chemical (doxapram at 2.5 mg kg -1 IV) or mechanical (gentle pressure to the corniculate process of the right arytenoid cartilage using a cotton bud) stimulation for enhanced assessment of laryngeal motion, in random order, with a 1 week wash-out period between treatments. If deemed inadequately anaesthetized, supplemental boli of thiopentone (1.8 mg kg -1 ), propofol (0.75 mg kg -1 ) or alfaxalone (0.4 mg kg -1 ) were administered. Assessment of number of arytenoid motions and vital breaths, among others, was initiated immediately after induction. Chemical (doxapram) and mechanical stimulation were begun 2 minutes after anaesthetic induction. Data were collected at 2, 3 and 5 minutes after anaesthetic induction and the Friedman rank-sum or repeated-measures analysis of variance tests were used when applicable for statistical analysis., Results: The duration of examination time was shorter among treatments combined with chemical stimulation (p=0.001). Examination time during induction was longer for alfaxalone-chemical (8.9 minutes) and -mechanical (10.9 minutes) compared to both induction with thiopentone-chemical (3.8 minutes) and propofol-chemical (4.0 minutes). The median number of arytenoid motions for both thiopentone (67) and propofol (59) induction combined with chemical stimulation was significantly higher in comparison to that of alfaxalone (1), thiopentone (2) and propofol (2), when combined with mechanical stimulation at 3 minutes after induction., Conclusion and Clinical Relevance: Among the regimens for assessing laryngeal motion assessed in the present study, combinations of thiopentone or propofol with doxapram are the most effective means of stimulating arytenoid motion and could improve the accuracy of diagnosis of laryngeal paralysis in dogs., (Copyright © 2019. Published by Elsevier Ltd.)

Some anesthetics including ketamine/xylazine and thiopental have been shown to alter the expression of genes related with inflammatory cytokines and chemokines in previous studies unassociated with wound healing, arising the question of whether commonly used anesthetics in wound healing models could interfere with the transcriptional responses of the genes associated with skin wound healing. The gene expression profile in wound biopsies of rats who received widely used anesthetics doses of intraperitoneal ketamine/xylazine (50 mg/kg and 10 mg/kg) or thiopental (50 mg/kg) in comparison with control rats was analyzed by monitoring the expression of genes effective on various phases of wound healing. The expression levels of 84 genes were determined on 3rd, 7th and 14th days of post-wounding using a qPCR array system. Of the genes either up or downregulated fivefolds or more, three (Egf, Col5a1 and Cxcl3) and two (Tgfa and Il2) genes were found to be the most responsive ones to ketamine/xylazine or thiopental anesthesia respectively in a period of 14 days after correction for multiple testing. However, up to 22 and 24 genes for ketamine/xylazine and thiopental were found to be differentially expressed in the same period without correction for multiple-comparisons testing (p < 0.05). In conclusion, our data suggest that ketamine/xylazine and thiopental may alter the transcriptional responses of some genes associated with wound healing in rats. We strongly suggest to consider the possible alteration effect of these anesthetics on gene expression in animal models of dermal wound healing.

Background: The time between anaesthetic induction and ECT stimulus administration has been hypothesised to significantly impact ictal EEG quality. In this study, our aim was to examine the effect of the time interval between anaesthetic induction and the ECT stimulus for ictal seizure quality in ECT sessions utilising thiopentone anaesthesia., Methods: 413 EEG traces from 42 patients, collected retrospectively, were manually rated using a quantitative-qualitative structured rating scale (indices including seizure amplitude, regularity, post-ictal suppression and general seizure quality). Linear Mixed Effects Models were used to analyse the effect of the anaesthetic-ECT time interval on seizure quality indices, seizure duration and orientation scores after ECT, controlling for patient and ECT treatment factors., Results: The anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p < 0.05), with longer times producing higher quality seizures. Seizure duration and orientation scores after ECT were not significantly influenced by the anaesthetic-ECT time interval. Age, anaesthetic dose, ECT type and ECT treatment number also had a significant impact on measures of seizure quality (p < 0.05)., Limitations: The effect of ventilation technique was not explicitly measured. Only manual ratings of ictal quality were analysed., Conclusions: The time between anaesthetic induction and ECT stimulus administration has a significant impact on the ictal EEG seizure quality observed, with thiopentone anaesthetic. These results are consistent with prior findings with propofol anaesthesia, and suggest a need for routine clinical monitoring of this time interval. This variable warrants consideration when interpreting ictal EEGs, which often informs subsequent dosing decisions., (Copyright © 2019. Published by Elsevier B.V.)

Background: In a military or terrorist scenario, combination of organophosphorus compounds (OP) poisoning with physical trauma requiring surgical treatment and thus general anaesthesia are possible. Previous in vitro studies showed an altered potency of relevant anaesthetics during cholinergic crisis. Hence, it is not clear, which anaesthetics are suitable to achieve the necessary stage of surgical anaesthesia in OP poisoning., Methods: In the present study, different anaesthetic regimens (ketamine-midazolam, propofol-fentanyl, thiopental-fentanyl), relevant in military emergency medicine, were examined in soman-poisoned rats. Clinical signs and cardiovascular variables were recorded continuously. Blood samples for acetylcholinesterase (AChE) activity were drawn. After euthanasia or death of the animals, brain and diaphragm were collected for cholinesterase assays., Results: Propofol-fentanyl and thiopental-fentanyl resulted in surgical anaesthesia throughout the experiments. With ketamine-midazolam, surgical anaesthesia without respiratory impairment could not be achieved in pilot experiments (no soman challenge) and was therefore not included in the study. Soman-poisoned and control animals required a comparable amount of propofol-fentanyl or thiopental-fentanyl. In combination with atropine, significantly less propofol was needed. Survival rate was higher with thiopental compared to propofol. Atropine improved survival in both groups. Blood and tissue AChE activities were strongly inhibited after soman administration with and without atropine treatment., Discussion: The current in vivo study did not confirm concerns of altered potency of existing anaesthetic protocols for the application of propofol or thiopental with fentanyl due to soman poisoning. Despite severe cholinergic crisis, sufficient anaesthetic depth could be achieved in all animals., Conclusion: Further experiments in in vivo models closer to human pharmaco- and toxicokinetics (e.g., swine) are required for confirmation of the initial findings and for improving extrapolation to humans.

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Anesthesia is necessary for most animal studies requiring invasive procedures. It is well documented that various types of anesthesia modulate a wide variety of important metabolic and functional processes in the body, and as such, represent a potential limitation in the study design. In the present study, we aimed to investigate the renal functional and metabolic consequences of 3 typical rodent anesthetics used in preclinical MRI: sevoflurane, inaction, and a mixture of fentanyl, fluanisone, and midazolam (FFM)., Methods: The renal effects of 3 different classes of anesthetics (inactin, servoflurane, and FFM) were investigated using functional and metabolic MRI. The renal glucose metabolism and hemodynamics was characterized with hyperpolarized [1- 13 C]pyruvate MRI and by DCE imaging., Results: Rats receiving sevoflurane or FFM had blood glucose levels that were 1.3-fold to 1.4-fold higher than rats receiving inactin. A 2.9-fold and 4.8-fold increased 13 C-lactate/ 13 C-pyruvate ratio was found in the FFM mixture anesthetized group compared with the sevoflurane and the inactin anesthetized groups. The FFM anesthesia resulted in a 50% lower renal plasma flow compared with the sevoflurane and the inactin anesthetized groups., Conclusion: This study demonstrates different renal metabolic and hemodynamic changes under 3 different anesthetics, using hyperpolarized MR in rats. Inactin and sevoflurane were found to affect the renal hemodynamic and metabolic status to a lesser degree than FFM. Sevoflurane anesthesia is particularly easy to induce and maintain during the whole anesthesia procedure, and as such, represents a good alternative to inaction, although it alters the blood glucose level., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background and Aim of the Work: electroconvulsive therapy is a psychiatric procedure requiring general anesthesia. The choice of the hypnotic agent is important because the success of the intervention is associated to the occurrence and duration of motor convulsion. However, all available anesthetic agents have anti-convulsant activity. We compared the effect of thiopental and propofol on seizures., Methods: We designed a retrospective study at Mood Disorders Unit of a teaching Hospital. Fifty-six consecutive patients undergoing electroconvulsive therapy were enrolled. Patients received fentanyl followed by either thiopental or propofol. We evaluated the incidence and the duration of seizure after electric stimulus at the first session of electroconvulsive therapy for each patient. Adverse perioperative effects were recorded., Results: Patients were 60±12.1 years old and 64% was female. There was a statistically significant higher number of patients who had motor convulsion activity in the thiopental group when compared to the propofol group (25 vs 13, p=0.023). Seizure duration was statistically significant longer in the thiopental group than in the propofol group (35 sec vs 11 sec, p=0.046). No hemodynamic instability, oxygen desaturation episodes, prolonged recovery time from anesthesia and adverse effects related to anesthesia were recorded., Conclusions: Thiopental induction has a favourable effect on seizure when compared to propofol in patients undergoing electroconvulsive therapy.

Barbiturates, commonly used as general anaesthetics, depress neuronal activity and thus cerebral metabolism. Moreover, they are likely to disrupt the metabolic support of astrocytes to neurons, as well as the uptake of nutrients from circulation. By employing 13 C magnetic resonance spectroscopy (MRS) in vivo at high magnetic field, we characterized neuronal and astrocytic pathways of energy metabolism in the rat cortex under thiopental anaesthesia. The neuronal tricarboxylic acid (TCA) cycle rate was 0.46 ± 0.02 µmol/g/min, and the rate of the glutamate-glutamine cycle was 0.09 ± 0.02 µmol/g/min. In astrocytes, the TCA cycle rate was 0.16 ± 0.02 µmol/g/min, accounting for a quarter of whole brain glucose oxidation, pyruvate carboxylase rate was 0.02 ± 0.01 µmol/g/min, and glutamine synthetase was 0.12 ± 0.01 µmol/g/min. Relative to previous experiments under light α-chloralose anaesthesia, thiopental reduced oxidative metabolism in neurons and even more so in astrocytes. Interestingly, total oxidative metabolism in the cortex under thiopental anaesthesia surpassed the rate of pyruvate production by glycolysis, indicating substantial utilisation of substrates other than glucose, likely plasma lactate. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Extracts of Desmodium adscendens (Sw) DC are used for the treatment of various diseases but limited toxicological evaluations have been done on the medicinal plant. This study investigates toxicity effects of the leave extract of D adscendens, and the possibility of drug-drug interaction of the plant extract when co-administered with other drugs. Oral administrations of leaf extract of D adscendens to white Wistar rats in an acute toxicity studies allowed the estimation of an LD 50 (median lethal dose) value of 1122 mg/kg body weight. In a subchronic toxicity studies, the plant extract caused a decrease in zoxazolamine paralysis time and prevented thiopentone from causing sleep in test animals compared to controls. Overall, the results are consistent with the plant extract being safe at the doses administered in humans. However, the induction of the CYP enzymes is an indication of a possible drug interaction when the plant extract is co-administered with other drugs.

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic electrophysiological features were preserved. Manipulations of the membrane potential and intracellular injection of chloride in neocortical neurons failed to reveal an augmented synaptic inhibition during the isoelectric condition. Consistent with the sensory responses recorded from comatose patients, large and highly reproducible somatosensory-evoked potentials could be generated on the inactive electrocorticogram in rats. Intracellular recordings revealed that the underlying neocortical pyramidal cells responded to sensory stimuli by complex synaptic potentials able to trigger action potentials. As in patients, sensory responses in the isoelectric state were delayed compared to control responses and exhibited an elevated reliability during repeated stimuli. Our findings demonstrate that during prolonged isoelectric brain state neurons and synaptic networks are dormant rather than excessively inhibited, conserving their intrinsic properties and their ability to integrate and propagate environmental stimuli., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Anesthesia is a major confounding factor in functional MRI (fMRI) experiments attributed to its effects on brain function. Recent evidence suggests that parameters obtained with resting-state fMRI (rs-fMRI) are coupled with anesthetic depth. Therefore, we investigated whether parameters obtained with rs-fMRI, such as functional connectivity (FC), are also directly related to blood-oxygen-level-dependent (BOLD) responses., Methods: A simple rs-fMRI protocol was implemented in a pharmacological fMRI study to evaluate the coupling between hemodynamic responses and FC under five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane). Temporal change in the FC was evaluated at 1-hour interval. Supplementary forepaw stimulation experiments were also conducted., Results: Under thiobutabarbital anesthesia, FC was clearly coupled with nicotine-induced BOLD responses. Good correlation values were also obtained under isoflurane and medetomidine anesthesia. The observations in the thiobutabarbital group were supported by forepaw stimulation experiments. Additionally, the rs-fMRI protocol revealed significant temporal changes in the FC in the α-chloralose, thiobutabarbital, and urethane groups., Conclusion: Our results suggest that FC can be used to estimate brain hemodynamic responsiveness to stimuli and evaluate the level and temporal changes of anesthesia. Therefore, analysis of the fMRI baseline signal may be highly valuable tool for controlling the outcome of preclinical fMRI experiments. Magn Reson Med 78:1136-1146, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Background: Seizure duration in electroconvulsive therapy (ECT) is positively related with patients' outcome. This study sought to investigate the impact of anesthetic management on seizure duration, and the impact of selected drugs (theophylline, remifentanil, S-ketamine) on seizure duration., Methods: Retrospective analysis of all patients undergoing ECT at our institution from January 2011 to April 2012 was performed based on electronic medical chart and review of existing quality improvement data. Patient data (N = 78), including gender, age, height, weight, and administered drugs, energy levels, and electroencephalic seizure duration were analyzed. Statistical analysis was performed using a generalized linear model., Results: A total of 78 patients (male = 39, female = 39, age 51 ± 12 years) were included. Average number of session was 10 ± 6 (1-30). In our patient population, theophylline administration was the only parameter, which significantly prolonged seizure duration, whereas S-ketamine, remifentanil, thiopental, age, sex, session or energy level had no significant effect., Conclusion: Theophylline can be a useful adjunct for patients with inadequate seizure duration. If there is a concomitant beneficial effect on patients' outcome needs to be investigated in further studies.

Objective: To compare the effects of thiopentone, propofol and alfaxalone on arytenoid cartilage motion and establish the dose rates to achieve a consistent oral laryngoscopy examination., Study Design: Randomised crossover study., Animals: Six healthy adult Beagle dogs., Methods: Each dog was randomly administered three induction agents with a 1-week washout period between treatments. Thiopentone (7.5 mg kg -1 ), propofol (3 mg kg -1 ) or alfaxalone (1.5 mg kg -1 ) was administered over 1 minute for induction of anaesthesia. If the dog was deemed inadequately anaesthetised, then supplemental boluses of 1.8, 0.75 and 0.4 mg kg -1 were administered, respectively. Continual examination of the larynx, using a laryngoscope, commenced once an adequate anaesthetic depth was reached until examination end point. The number of arytenoid motions and vital breaths were counted during three time periods and compared over time and among treatments. Data were analysed using Friedman and Mann-Whitney U tests, Spearman rho and a linear mixed model with post hoc pairwise comparison with Tukey correction., Results: The median (range) induction and examination times were 2.8 (2.0-3.0), 2.7 (2.0-3.3) and 2.5 (1.7-3.3) minutes (p = 0.727); and 14.1 (8.0-41.8), 5.4 (3.3-14.8) and 8.5 (3.8-31.6) minutes (p = 0.016) for thiopentone, propofol and alfaxalone, respectively. The median dose rates required to achieve an adequate anaesthetic depth were 6.3 (6.0-6.6), 2.4 (2.4-2.4) and 1.2 (1.2-1.2) mg kg -1  minute -1 , respectively. There was no significant difference for the total number of arytenoid motions (p = 0.662) or vital breaths (p = 0.789) among induction agents., Conclusion and Clinical Relevance: The number of arytenoid motions were similar among the induction agents. However, at the dose rates used in this study, propofol provided adequate conditions for evaluation of the larynx with a shorter examination time which may be advantageous during laryngoscopy in dogs., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Reasons for Performing Study: There is limited information on clinical use of the new injectable anaesthetic agent alfaxalone in Thoroughbred horses., Objectives: To compare anaesthetic induction and recovery characteristics and cardiopulmonary responses between alfaxalone, ketamine and thiopental in Thoroughbred horses premedicated with medetomidine and midazolam., Study Design: Randomised blinded experimental cross-over study., Methods: Six Thoroughbred horses were anaesthetised 3 times with alfaxalone 1 mg/kg bwt, ketamine 2.5 mg/kg bwt or thiopental 4 mg/kg bwt after premedication with medetomidine 6 μg/kg bwt and midazolam 20 μg/kg bwt. Qualities of anaesthetic induction and recovery were scored on a scale of 1 (poor) to 5 (excellent). Induction time and recovery time were recorded. Cardiopulmonary values (heart rate, respiratory rate, arterial blood pressures, and arterial blood gases) were recorded throughout anaesthesia. Data were analysed with nonparametric methods., Results: The anaesthetic induction (P = 0.2) and recovery (P = 0.1) quality scores (median, range) were not different amongst protocols and were 4.0, 3-5; 5.0, 4-5; 4.5, 3-5; and 4.5, 3-5; 3.5, 2-5; 4.0, 2-5 for alfaxalone, ketamine and thiopental, respectively. Induction time for ketamine (67, 53-89 s) was significantly longer than that for alfaxalone (49, 40-51 s, P = 0.01) and thiopental (48, 43-50 s, P = 0.01). Time to standing for alfaxalone (44, 40-63 min, P = 0.01) and thiopental (39, 30-58 min, P = 0.01) was significantly longer than that for ketamine (25, 18-26 min). Cardiovascular values were maintained within the clinically acceptable level throughout anaesthesia. Respiratory rate significantly decreased during anaesthesia for all 3 drugs; however, spontaneous breathing did not disappear, and PaCO 2 values were maintained at approximately 50 mmHg., Conclusions: All 3 drugs showed similar effects in relation to anaesthetic induction and recovery qualities and cardiopulmonary responses. However, alfaxalone and thiopental prolonged recovery time compared with ketamine., (© 2015 EVJ Ltd.)

Study Objective: Opioids are integral part of anesthesia induction, but information on optimal dosing is limited. We aimed to determine doses of alfentanil needed to eliminate increases in 5 autonomic response variables (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial blood pressure [ABP], and heart rate) during rapid-sequence induction of anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg., Design: Prospective, randomized, observer-blinded, interventional clinical study., Setting: Large academic institution., Patients: Eighty-four healthy patients, aged 18 to 55 years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40, 50, and 60 μg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg, administered in rapid succession (15 seconds). Laryngoscopy was initiated 40 seconds after rocuronium, and tracheal intubation was concluded within 15 seconds thereafter., Measurements: An indwelling radial artery catheter was used for hemodynamic monitoring and blood sampling. Relationships between alfentanil dose and response variables were tested with linear regression, and the influence of covariates (sex, body weight, and age) was determined. Alfentanil dose needed to prevent increases in ABP >10% above baseline with 95% probability was estimated with logistic regression., Main Results: Significant relationships were determined between alfentanil dose and response variables. Clinically interesting influence of covariates was not found. Alfentanil 55 μg/kg was needed to prevent increases in ABP postintubation >10% above baseline with 95% probability. One individual needed a bolus of vasopressor postintubation., Conclusions: Optimal control of autonomic responses during rapid-sequence induction was achieved with clinically relevant doses of alfentanil in healthy patients anesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Growing data support peripheral opioid antinociceptive effects, particularly in inflammatory pain models. Here, we examined the antinociceptive effects of subcutaneously administered, recently synthesized 14-O-methylmorphine-6-O-sulfate (14-O-MeM6SU) compared with morphine-6-O-sulfate (M6SU) in a rat model of inflammatory pain induced by an injection of complete Freund's adjuvant and in a mouse model of visceral pain evoked by acetic acid. Subcutaneous doses of 14-O-MeM6SU and M6SU up to 126 and 547 nmol/kg, respectively, produced significant and subcutaneous or intraplantar naloxone methiodide (NAL-M)-reversible antinociception in inflamed paws compared with noninflamed paws. Neither of these doses significantly affected thiobutabarbital-induced sleeping time or rat pulmonary parameters. However, the antinociceptive effects of higher doses were only partially reversed by NAL-M, indicating contribution of the central nervous system. In the mouse writhing test, 14-O-MeM6SU was more potent than M6SU after subcutaneous or intracerebroventricular injections. Both displayed high subcutaneous/intracerebroventricular ED50 ratios. The antinociceptive effects of subcutaneous 14-O-MeM6SU and M6SU up to 136 and 3043 nmol/kg, respectively, were fully antagonized by subcutaneous NAL-M. In addition, the test compounds inhibited mouse gastrointestinal transit in antinociceptive doses. Taken together, these findings suggest that systemic administration of the novel compound 14-O-MeM6SU similar to M6SU in specific dose ranges shows peripheral antinociception in rat and mouse inflammatory pain models without central adverse effects. These findings apply to male animals and must be confirmed in female animals. Therefore, titration of systemic doses of opioid compounds with limited access to the brain might offer peripheral antinociception of clinical importance., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Determination of left ventricular ejection fraction (LVEF) using in vivo imaging is the cardiac functional parameter most frequently employed in preclinical research. However, there is considerable conflict regarding the effects of anesthetic agents on LVEF. This study aimed at assessing the effects of various anesthetic agents on LVEF in hamsters using transthoracic echocardiography. Twelve female hamsters were submitted to echocardiography imaging separated by 1-week intervals under the following conditions: 1) conscious animals, 2) animals anesthetized with isoflurane (inhaled ISO, 3 L/min), 3) animals anesthetized with thiopental (TP, 50 mg/kg, intraperitoneal), and 4) animals anesthetized with 100 mg/kg ketamine plus 10 mg/kg xylazine injected intramuscularly (K/X). LVEF obtained under the effect of anesthetics (ISO=62.2±3.1%, TP=66.2±2.7% and K/X=75.8±1.6%) was significantly lower than that obtained in conscious animals (87.5±1.7%, P<0.0001). The K/X combination elicited significantly higher LVEF values compared to ISO (P<0.001) and TP (P<0.05). K/X was associated with a lower dispersion of individual LVEF values compared to the other anesthetics. Under K/X, the left ventricular end diastolic diameter (LVdD) was increased (0.60±0.01 cm) compared to conscious animals (0.41±0.02 cm), ISO (0.51±0.02 cm), and TP (0.55±0.01 cm), P<0.0001. The heart rate observed with K/X was significantly lower than in the remaining conditions. These results indicate that the K/X combination may be the best anesthetic option for the in vivo assessment of cardiac systolic function in hamsters, being associated with a lower LVEF reduction compared to the other agents and showing values closer to those of conscious animals with a lower dispersion of results.

Although many in vitro studies demonstrated that thiopental sodium (TPS) is a promising neuroprotective agent, clinical attempts to use TPS showed mainly unsatisfactory results. We investigated the neuroprotective effects of TPS against hypoxic insults (HI), and the responses of the neurons to l-glutamate and acetylcholine application. Neurons prepared from E17 Wistar rats were used after 2weeks in culture. The neurons were exposed to 12-h HI with or without TPS. HI-induced neurotoxicity was evaluated morphologically. Moreover, we investigated the dynamics of the free intracellular calcium ([Ca(2+)]i) in the surviving neurons after HI with or without TPS pretreatment following the application of neurotransmitters. TPS was neuroprotective against HI according to the morphological examinations (0.73±0.06 vs. 0.52±0.07, P=0.04). While the response to l-glutamate was maintained (0.89±0.08 vs. 1.02±0.09, P=0.60), the [Ca(2+)]i response to acetylcholine was notably impaired (0.59±0.02 vs. 0.94±0.04, P<0.01). Though TPS to cortical cultures was neuroprotective against HI morphologically, the [Ca(2+)]i response not to l-glutamate but to acetylcholine was impaired. This may partially explain the inconsistent results regarding the neuroprotective effects of TPS between experimental studies and clinical settings., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In recent years, discussion around memory modification interventions has gained attention. However, discussion around the use of memory interventions in the criminal justice system has been mostly absent. In this paper we start by highlighting the importance memory has for human well-being and personal identity, as well as its role within the criminal forensic setting; in particular, for claiming and accepting legal responsibility, for moral learning, and for retribution. We provide examples of memory interventions that are currently available for medical purposes, but that in the future could be used in the forensic setting to modify criminal offenders' memories. In this section we contrast the cases of (1) dampening and (2) enhancing memories of criminal offenders. We then present from a pragmatic approach some pressing ethical issues associated with these types of memory interventions. The paper ends up highlighting how these pragmatic considerations can help establish ethically justified criteria regarding the possibility of interventions aimed at modifying criminal offenders' memories.

In case of military or terrorist use of organophosphorus (OP) compounds victims are likely to suffer from not only intoxication but physical trauma as well. Appropriate emergency care may therefore include general anesthesia to allow life-saving surgical intervention. Since there is evidence that drug potency and efficacy of several anesthetics are attenuated by high concentrations of acetylcholine in the CNS, this study was designed to evaluate the anesthetic actions of thiopental during cholinergic overstimulation. Making use of organotypic slice cultures derived from the mouse neocortex, drug effects were assessed by extracellular voltage recordings of network activity at basal cholinergic tone and during simulated cholinergic crisis (high cholinergic tone). The latter was achieved by inhibition of acetylcholinesterases via soman and an ambient acetylcholine concentration of 10μM. The induction of cholinergic crisis in vitro increased the network activity of cortical neurons significantly. Surprisingly, differences in network activity between basal and high cholinergic tone became less pronounced with rising concentrations of thiopental and drug potency and efficacy were almost equivalent. These results clearly distinguish thiopental from previously tested general anesthetics and make it a promising candidate for in vivo studies to identify suitable anesthetics for victims of OP intoxication., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The effect of etomidate administration on the adrenal cortex in obese patients is still unclear. The objective of the study was to determine the influence of a single dose of etomidate on cortisol secretion in the morbidly obese., Methods: 127 healthy patients were enrolled into the study. Data from 82 patients scheduled for elective laparoscopic surgery were analyzed. 62 of them were morbidly obese, while 20 had normal body mass. The participants were divided equally into etomidate and thiopental groups, depending on the kind of intravenous anaesthetic used for the induction of anaesthesia. Each patient's serum cortisol concentration was measured five times: on the day before surgery (sample A), two hours after the induction of anaesthesia (sample B), after a short tetracosactide test (sample C), 24 hours after the induction of anaesthesia (sample D), and after a second short stimulation test (sample E)., Results: The mean cortisol concentration in obese patients in the etomidate group was lower two hours after the induction of anaesthesia (sample B, P < 0.001), and 30 minutes after the first tetracosactide test (sample C, P < 0.001) compared to obese patients in the thiopental group. There were no differences between the groups in sample A (P = 0.833), D (P = 0.614) and E (P = 0.769). We found no changes in haemodynamic parameters between both groups., Conclusions: Etomidate decreased serum cortisol concentration and decreased reactivity to tetracosactide both in morbidly obese and in normal weight patients. This effect was reversible within 24 hours.

Aim: We hypothesized that certain effects of the general anaesthetic thiopental are dependent on NO-related mechanisms, which were consequently counteracted by stable gastric pentadecapeptide BPC 157., Main Methods: (1) All rats intraperitoneally received thiopental (20, 30, 40, and 50 mg/kg) while medication BPC 157 (10 μg/kg, 10 ng/kg, and 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (2) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), L-NAME (10 mg/kg) and L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L-arginine, alone and/or combined, were applied at 20 min before thiopental., Key Findings: (1) BPC 157 own effect on thiopental anaesthesia: BPC 157 (10 ng/kg and 10 μg/kg) caused a significant antagonism of general anaesthesia produced by thiopental with a parallel shift of the dose-response curve to the right. (2) L-NAME-L-arginine-BPC 157 interrelations: L-NAME: Thiopental-induced anaesthesia duration was tripled. L-arginine: Usual thiopental anaesthesia time was not influenced. Active only when given with L-NAME or BPC 157: potentiating effects of L-NAME were lessened, not abolished; shortening effect of BPC 157: abolished. BPC 157 and L-NAME: Potentiating effects of L-NAME were abolished. BPC 157 and L-NAME and L-arginine: BPC 157 +L-NAME +L-arginine rats exhibited values close to those in BPC 157 rats., Significance: Thiopental general anaesthesia is simultaneously manipulated in both ways with NO system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction) and L-arginine (interference with L-NAME and BPC 157).

Background: Electroconvulsive therapy (ECT) is one of the available and the most effective therapies for the treatment of resistant depression. Considering the crucial role of seizure duration on therapeutic response in patients treated with ECT, this study aimed to compare the effect of ketamine and sodium thiopental anesthesia during ECT for treatment of patients with drug-resistant major depression (DRMD)., Materials and Methods: In a double-blind randomized clinical trial, 160 patients with DRMD were selected consequently and were assigned randomly into two groups including ketamine 0.8 mg/kg and sodium thiopental 1.5 mg/kg. The seizure duration, recovery time, and the side effects of anesthesia were evaluated after 1-h after anesthesia. Data of recovery time and complication collected in 2 nd , 4 th , 6 th , and 8 th ECT. Depression was assessed by Hamilton depression scale., Results: The results indicated that ketamine and sodium thiopental had a significant effect on the reduction of depression scores in patients with DRMD (P < 0.05). Complications such as a headache, nausea, pain at the injection site, short-term delirium, and long-term delirium were higher in ketamine group (P > 0.05). But ketamine was more effective in improvement of depression score and increasing systolic and diastolic blood pressure (P < 0.05). The mean of seizure duration showed a decreasing trend and was significant between two study groups (P < 0.05)., Conclusion: Anesthesia induced by ketamine during ECT therapy increased blood pressure and seizure duration. Therefore, due to lower medical complication and attack rate of seizure, ketamine is an appropriate option for anesthesia with ECT in patients with DRMD.

Background: An individualized approach to maximize electroconvulsive therapy (ECT) efficacy and minimize cognitive side effects is to treat patients relative to their seizure threshold (ST). However, although Right Unilateral-Ultrabrief (0.3 ms) (RUL-UB) ECT is increasingly used in clinical settings as an effective form of ECT with minimal cognitive effects, there is sparse data regarding predictors of ST., Objective: To analyze the relationship between ST and clinical and demographic factors in a sample of patients treated with RUL-UB ECT., Methods: Clinical, demographic and ECT data from 179 patients in ECT research studies were examined. Seizure threshold was titrated at the first ECT session. ECT was performed with a Thymatron(®) or Mecta(®) device, with thiopentone (2.5-5 mg/kg) or propofol (1-2 mg/kg) anaesthesia. Medications taken at the time of ST titration were documented. The association between ST and candidate predictor variables was examined with regression analysis., Results: Multiple regression analyses showed that 34% of the variance in ST (P < 0.001) could be predicted. Older age (R(2) = 0.194, P < 0.001), propofol (vs thiopentone) (R(2) = 0.029, P ≤ 0.01) and higher anaesthetic dose (mg in propofol equivalents) (R(2) = 0.029, P < 0.05) were found to be predictors of higher initial ST. Treatment with lithium (R(2) = 0.043, P < 0.01) and study site (R(2) = 0.019, P < 0.05) significantly predicted lower initial ST., Conclusions: Empirical titration is recommended for accurate determination of ST in patients receiving RUL-UB ECT. Novel findings of this study are that propofol anaesthesia resulted in higher ST than thiopentone and concomitant treatment with lithium treatment lowered ST., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: It remains to be elucidated whether the Trendelenburg position increases intracranial pressure (ICP). ICP can be evaluated by measuring the sonographic optic nerve sheath diameter (ONSD). We investigated the effect of the isolated Trendelenburg position on ONSD in patients undergoing robot-assisted laparoscopic radical prostatectomy. Additionally, we evaluated the effect of the Trendelenburg position combined with pneumoperitoneum on ONSD., Methods: Twenty-one patients scheduled for robot-assisted laparoscopic radical prostatectomy were enrolled. Sonographic ONSDs and hemodynamic parameters were measured at specific time points: in the supine position after induction of anesthesia, 3 min after the steep Trendelenburg position (35° incline), 3 min after the steep Trendelenburg position combined with pneumoperitoneum, and in the supine position after desufflation of the pneumoperitoneum., Results: The ONSD 3 min after the steep Trendelenburg position was significantly higher than that of the supine position after induction of anesthesia (5.1 ± 0.3 mm vs. 4.5 ± 0.4 mm). In addition, the ONSD 3 min after the steep Trendelenburg position combined with pneumoperitoneum was higher than that of the supine position after induction of anesthesia (4.9 ± 0.4 mm vs. 4.5 ± 0.4 mm). The ONSD in the supine position after desufflation of the pneumoperitoneum was similar to that in the supine position after induction of anesthesia., Conclusions: Use of the isolated steep Trendelenburg position, for even a short duration, increased the sonographic ONSD, providing a better understanding of the effect of only a transient steep Trendelenburg position on ONSD as a surrogate measure for ICP.

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group's claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR.

Objective: We aimed to investigate whether mitochondrial ATP-sensitive potassium (mitoKATP) channels play any role on cardiovascular effects of thiopental (TP) or ketamine (K) anesthesia in rats., Background: mitoKATP channels are the end-effectors of cardioprotection induced by some anesthetics. TP and K are the most frequently used anesthetics with their own cardiovascular effects in experimental studies. To the best of our knowledge, there is no study investigating the cardiovascular effects of TP and K associated with mitoKATP channels., Materials and Methods: The experimental groups: TP control, K/Xylazine (X) control, TP+5-hydroxydecanoate (5-HD; mitoKATP channel blocker) and K/X+5-HD. Mean arterial blood pressure (MABP), heart rate (HR) and standard limb lead II ECG were recorded and arrhythmia parameters were evaluated., Results: Blockage of mitoKATP channels by 5-HD increased MABP and decreased HR in the TP+5-HD and K/X+5-HD groups, respectively. 5-HD caused an increase in ventricular ectopic beat (VEB) incidence. Moreover, VEB incidence was significantly different in TP+5-HD (100%) than K/X+5-HDgroup (66.6%) and ventricular tachycardia was only seen in TP+5-HD (incidence was 88.3%)., Conclusion: mitoKATP channels play different roles in influencing cardiovascular effects of K/X and TP anesthesia in rats. The differences in hemodynamic parameters and arrhythmia scores of these anesthetics should be considered when they are used in an experimental study associated with mitoKATP channels (Fig. 3, Ref. 35).

Background/aim: To investigate the influence of thiopental (85 mg/kg, intraperitoneally (ip)), and ketamine+xylazine (ketamine 75 mg/kg and xylazine 8 mg/kg, ip) anesthesia on the incidence and duration of ischemia/reperfusion-induced arrhythmias., Materials and Methods: Myocardial ischemia was induced by a 6-min ligation of the left anterior descending coronary artery, followed by a 6-min reperfusion. Measurements were taken of the incidence and duration of ventricular arrhythmias, the mean arterial blood pressure and heart rate, and the pressure rate-product (as an.index of myocardial oxygen consumption)., Results: The arrhythmia score and the incidence of ventricular fibrillation and tachycardia were significantly decreased in the ketamine+xylazine-anesthetized rats compared with the thiopental-anesthetized group (arrhythmia score: 2.0 ± 2.1 versus 3.7 ± 1.2, P < 0.05). The heart rate was significantly lower in the ketamine+xylazine group during the entire experiment, whilst the pressure-rate product was also significantly lower in the ketamine+xylazine group at different time points of the ischemia and reperfusion periods., Conclusion: Ketamine+xylazine anesthesia has a strong antiarrhythmic effect and an apparent depressive action on the heart rate and the myocardial oxygen consumption index. Therefore, ketamine+xylazine anesthesia is not appropriate for the evaluation of possible antiarrhythmic agents. Thiopental anesthesia is preferable to ketamine+xylazine anesthesia in the in vivo ischemia-reperfusion arrhythmia model.