Serotonin, estrus, and social context influence c-Fos immunoreactivity in the inferior colliculus.

A fundamental task of sensory systems is to extract relevant social information from a range of environmental stimuli in the face of changing behavioral contexts and reproductive states. Neuromodulatory pathways that interact with such contextual variables are 1 mechanism for achieving this. In the mouse inferior colliculus (IC), a midbrain auditory region, the neuromodulator serotonin increases in females interacting with courting males, but events downstream of serotonin release have not been investigated. Here, we manipulated serotonin levels in female mice with the serotonin releaser fenfluramine or the serotonin depleter para-chlorophenylalaninemethyl ester (pCPA). Females were then exposed to an empty cage, a male partner, or a playback of courtship vocalizations, and the numbers of neurons in the IC with positive immunoreactivity for the immediate early gene product c-Fos were measured. The effects of drug treatments depended on social context and estrous state. Fenfluramine had greater effects in the nonsocial than in the partner social treatments. Females in proestrus or estrus and given fenfluramine had higher densities of c-Fos immunoreactive neurons, while females in diestrus had fewer immunoreactive neurons. The drug pCPA had the expected opposite effect of fenfluramine, causing a decreased response in pro/estrus females and an increased response in diestrus females. These findings show that the effects of serotonin on c-Fos activity in the IC of females is dependent on both external context and reproductive state, and suggest that these effects occur downstream of serotonin release. (PsycINFO Database Record

Inhalation anesthesia is preferable for recording rat cardiac function using an electrocardiogram.

The effects of inhalation anesthesia (2% isoflurane, sevoflurane, or enflurane) and intraperitoneal anesthesia with pentobarbital (65 mg/kg) were compared in rats using an electrocardiogram (ECG) and determination of blood oxygen saturation (SPO2) levels. Following inhalation anesthesia, heart rate (HR) and SPO2 were acceptable while pentobarbital anesthesia decreased HR and SPO2 significantly. This indicates that inhalation anesthesia is more preferable than pentobarbital anesthesia when evaluating cardiovascular factors. Additionally, pentobarbital significantly increased HR variability (HRV), suggesting a regulatory effect of pentobarbital on the autonomic nervous system, and resulted in a decreased response of the baro-reflex system. Propranolol or atropine had limited effects on ECG recording following pentobarbital anesthesia. Taken together, these data suggest that inhalation anesthesia is suitable for conducting hemodynamic analyses in the rat.

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats.

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R(2) = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R(2) = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients).

Airway management using a supraglottic airway device without endotracheal intubation for positive ventilation of anaesthetized rats.

Endotracheal intubation is often necessary for positive pressure ventilation of rats during open thoracic surgery. Since endotracheal intubation in rats is technically difficult and is associated with numerous complications, many techniques using various devices have been described in the scientific literature. In this study, we compared the effectiveness of airway management of a home-made supraglottic airway device (SAD), which is cheap to fabricate and easy to place with that of an endotracheal intubation tube in enflurane-anaesthetized rats. Twenty male Sprague-Dawley rats (200-300 g) were randomly assigned to two equal groups for positive pressure mechanical ventilation using either the SAD or an endotracheal intubation tube. The carotid artery of each rat was cannulated for continuous blood pressure measurements and obtaining blood samples for determination of oxygen tension, carbon dioxide tension, and blood acidity before, during and after SAD placement or endotracheal intubation. Proper placement of the SAD was confirmed by observing chest wall movements that coincided with the operation of the mechanical ventilator. No complications and adverse events were encountered in the rats in which the SAD was placed, during SAD placement and immediate removal, during their mechanical ventilation through the SAD, and one week after SAD removal. From the results of blood gas analyses, we conclude that anaesthetized rats can be successfully ventilated using an SAD for open thoracic surgery.

Involvement of kainate receptors in the analgesic but not hypnotic effects induced by inhalation anesthetics.

In the present study, the role of kainate (KA) receptors in hypnosis and analgesia induced by emulsified inhalation anesthetics was investigated. A mouse model of hypnosis and analgesia was established by an intraperitoneal injection of emulsified enflurane, isoflurane or sevoflurane. We intracerebroventricularly (icv) or intrathecally (it) administered KA, a KA receptor agonist to mice. The effects of the KA on the sleep time were observed using a hypnosis test, and the tail-withdrawal latency was analyzed using the tail-withdrawal test. In the hypnosis test, KA (2.5, 5 or 10 ng; icv administered) treatment had no distinctive effects on the sleep time of mice treated with emulsified inhalation anesthetics. In the tail-withdrawal test, KA (0.2, 0.4 or 0.8 ng; it administered) treatment significantly and dose-dependently decreased the tail-withdrawal latency of mice treated with emulsified anesthetics. These results suggested that KA receptors may modulate the analgesic but not hypnotic effects induced by emulsified enflurane, isoflurane or sevoflurane.

Subcutaneous injection of inhaled anesthetics produces cutaneous analgesia.

PURPOSE: Previous investigations suggest that inhaled anesthetics may produce cutaneous analgesia. The objective of this study was to evaluate whether inhaled anesthetics have a direct analgesic effect on skin. METHODS: We conducted subcutaneous injections of one of three inhaled anesthetics (halothane, isoflurane, and enflurane) or one of two local anesthetics (lidocaine and procaine) at various dosages in rats (n=6 rats, for each dose of each drug). Subcutaneous injections of vehicles (saline or olive oil) were used as controls (n=6 rats for each vehicle). We constructed concentration-response curves, wherein the concentrations of drugs tested in subcutaneous tissue fluid were estimated by calculation, and the cutaneous analgesic effects of drugs were evaluated by pinprick tests on skin. RESULTS: Like local anesthetics, subcutaneous injection of inhaled anesthetics produced concentration-dependent, cutaneous analgesia which attained maximum (complete cutaneous analgesia) at high concentration. This effect was reversible and localized in the area of injection. On the basis of 50% effective concentration, the ranking of potencies was lidocaine>halothane>isoflurane>enflurane>procaine (P<0.05 for all differences). Subcutaneous injections of vehicles did not produce cutaneous analgesia. CONCLUSIONS: Like local anesthetics (lidocaine and procaine), subcutaneous injections of inhaled anesthetics (halothane, isoflurane, and enflurane) produced a concentration-dependent, cutaneous, analgesic effect at the site of injection. Inhaled anesthetics have a direct analgesic effect on skin.

Enflurane requirement for blocking adrenergic responses to incision in infants and children.

BACKGROUND: Enflurane is one of the most commonly used inhaled anesthetics in China, but its requirement to block adrenergic responses after skin incision in pediatric patients is still unknown. This study was to determine the minimum alveolar anesthetic concentration (MAC) of potent inhaled anesthetics required to blunt the adrenergic response to skin incision of enflurane (MACBAR) in infants and children. METHODS: Twenty-eight patients, 10 infants (6-12 months) and 18 young children (1-6 years), were studied. The 18 children were randomly assigned into two groups, with or without fentanyl. Anesthesia was induced with 3 mg/kg propofol and 0.15 mg/kg vecuronium, and maintained with enflurane in 100% oxygen. Fentanyl (3 microg/kg) was given intravenously 5 minutes before incision for the patients of fentanyl group. The "up and down" method (with 0.3 MAC as a step size and 1 MAC as the start dose) was applied to determine MACBAR. The response was considered positive if the mean arterial pressure (MAP) or heart rate (HR) increased > or =15% after incision. The MACBAR was calculated as the mean of four independent cross-over responses in each group. RESULTS: MACBAR of enflurane in children of 1-6 years old was 3.2% (95% CI, 2.8%-3.6%) and was reduced to 2.2% (95% CI, 1.8%-2.5%) by 3 microg/kg fentanyl. In infants of 6-12 months old, the MACBAR of enflurane was 3.4% (95% CI, 3.0%-3.8%). CONCLUSIONS: MACBAR of enflurane in infants older than 6 months is similar to that in young children. The MACBAR of enflurane decreases with co-administration of fentanyl in the pediatric population.

[Effect of volatile inhalational anesthetics on cerebral blood volume and oxygen status in children].

The investigation evaluated the effect of various volatile anesthetics on cerebral blood volume and oxygen status in sick children at the stage of anesthesia induction. Ninety-two children were distributed into 3 groups: Groups 1 (n = 36) and 2 (n = 24) underwent stepwise induction with halothane and enflurane, respectively. Group 3 (n = 32) had vital capacity rapid inhalation induction with sevoflurane. Cerebral oximetry (NIRS method) was used to measure the content of hydroxyhemoglobin, deoxyhemoglobin, the total level of hemoglobin and to assess regional cerebral tissue saturation (rSO2). Halothane was ascertained to increase cerebral blood volume by 20.5% whereas enflurane and sevoflurane increased it only by 8.8 and 9.0%, respectively. In all cases, the value of rSO2 remained comparatively high, by exceeding the baseline level by 3-5%.

Spinal N-methyl-D-aspartate receptors may mediate the analgesic effects of emulsified halogenated anesthetics.

The present study was designed to investigate the relationship between spinal cord N-methyl-D-aspartate (NMDA) receptors and the analgesic effects of emulsified halogenated anesthetics. After having established the mouse model of analgesia by intraperitoneally or subcutaneously injecting appropriate doses of emulsified enflurane, isoflurane or sevoflurane, we intrathecally injected different doses of NMDA and then observed the effects on the pain threshold using the hot-plate test and the acetic acid-induced writhing test. The results showed that intrathecal injection of NMDA (2.5, 5 and 10 ng) did not affect the pain threshold on the hot-plate test or the writhing times in conscious mice (p > 0.05); in contrast, NMDA (2.5, 5 and 10 ng intrathecally) can significantly and dose dependently decrease the pain threshold on the hot-plate test (p < 0.05 or p < 0.01) and increase the writhing times (p < 0.05 or p < 0.01) in the mice treated with emulsified anesthetics. These results suggest that spinal NMDA receptors may be important targets for the analgesic effects of emulsified enflurane, isoflurane and sevoflurane.

[Effects of volatile anesthetics on cortical somatosensory evoked potential and Bispectral index].

OBJECTIVE: To improve the anesthetic environment in monitoring short-latency somatosensory evoked potentials (SSEP) during operation, we compared the effects of different anesthetics on SSEP and Bispectral index (BIS), which aim to select suitable anesthetics and their doses used intraoperatively. METHODS: 60 ASA I-II patients undergoing elective neurosurgery were randomly allocated into three groups: enflurane, isoflurane and desflurane group. The concentration of each volatile anesthetic was increased step by step from 0 to end-tidal 0.3, 0.5, 0.75, 1.0 and 1.5 MAC. The changes of cortical SSEP component N20 were recorded as well as Bispectral index (BIS) monitoring. The effects of three volatile anesthetics in various concentrations on short-latency SSEP and BIS were investigated. RESULTS: All three volatile anesthetics significantly decreased N20 amplitude and prolonged N20 latency. The N20 waveform disappeared in some patients when the end-tidal concentration of enflurane reached 1.0 MAC, it occurred when that of isoflurane or desflurane was at 1.5 MAC. BIS monitoring showed BIS values were all under 60 when at 1.0 MAC in three group. For some patients in enflurane group and desflurane group, BIS values were above 60 (45-64, 44-61, respectively) when at 0.75 MAC, while those in isoflurane group were still less than 60 (39-58). And the amplitude or latency of cortical SSEP correlated poorly with BIS. CONCLUSION: The effects of three volatile anesthetics on SSEP and BIS are significant in dose-dependent manner. Anesthetic regimen of 0.75 MAC isoflurane for intraoperative cortical SSEP monitoring may be optimal. It seemed that the correlation between BIS and short-latency SSEP was poor, although both are associated with the effects of anesthetics on cerebral cortex.

Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane.

Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT) play a critical role in generation of low-amplitude oscillatory bursting involving mutually interconnected cortical and thalamic neurones, and are implicated in the state of arousal and sleep, as well as seizures. Here we show in brain slices from young rats that two kinetically different T-type Ca2+ currents exist in nRT neurones, with a slowly inactivating current expressed only on proximal dendrites, and fast inactivating current predominantly expressed on soma. Nickel was about twofold more potent in blocking fast (IC50 64 microM) than slow current (IC50 107 microM). The halogenated volatile anaesthetic enflurane blocked both currents, but only the slowly inactivating current was affected in voltage-dependent fashion. Slow dendritic current was essential for generation of low-threshold Ca2+ spikes (LTS), and both enflurane and nickel also suppressed LTS and neuronal burst firing at concentrations that blocked isolated T currents. Differential kinetic properties of T currents expressed in cell soma and proximal dendrites of nRT neurones indicate that various subcellular compartments may exhibit different membrane properties in response to small membrane depolarizations. Furthermore, since blockade of two different T currents in nRT neurones by enflurane and other volatile anaesthetics occurs within concentrations that are relevant during clinical anaesthesia, our findings suggest that these actions could contribute to some important clinical effects of anaesthetics.

Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction in rabbits.

BACKGROUND: Preconditioning against myocardial infarction by volatile anesthetics is well known. The authors tested the hypothesis that new emulsified formulations of halogenated anesthetics administered intravenously reduce myocardial infarct size when administered either 1 or 24 h before prolonged ischemia and reperfusion. METHODS: Pentobarbital-anesthetized rabbits (n = 39) were instrumented for measurement of hemodynamics and randomly assigned to receive intravenous saline (control), lipid vehicle, or infusions (3.5 ml . kg . h for 30 min) of emulsified isoflurane (6.9%), enflurane (7.1%), or sevoflurane (7.5%). Infusions were discontinued 30 min before a 30-min coronary occlusion and 3 h of reperfusion. In three additional groups, conscious rabbits (n = 21) received saline, lipid vehicle, or emulsified sevoflurane (7.5%) infusions (3.5 ml . kg . h for 30 min) 24 h before ischemia and reperfusion. Infarct size was determined using triphenyltetrazolium staining. RESULTS: Lipid vehicle produced transient increases in heart rate, whereas emulsified volatile anesthetics had no effect on hemodynamics before coronary occlusion. Lipid vehicle did not affect infarct size (38 +/- 2% of the area at risk; mean +/- SEM) as compared with saline control (41 +/- 4%). In contrast, emulsified isoflurane, enflurane, and sevoflurane reduced infarct size (20 +/- 3%, 20 +/- 3%, and 21 +/- 2% of the area at risk, respectively; P < 0.05). Administration of lipid vehicle or emulsified sevoflurane did not produce sedation or respiratory depression in conscious rabbits. Emulsified sevoflurane (18 +/- 2%) but not lipid vehicle (44 +/- 2%) reduced infarct size as compared with control in delayed preconditioning experiments. CONCLUSIONS: Intravenous emulsified halogenated anesthetics produce acute and delayed preconditioning against myocardial infarction.

Degrees of aversion shown by rats and mice to different concentrations of inhalational anaesthetics.

The distress associated with the induction of anaesthesia with halothane, isoflurane, enflurane and carbon dioxide was investigated in rats and mice by measuring the level of aversion they displayed on exposure to low, medium and high concentrations of these agents. The animals were exposed to each agent in a test chamber containing air or gas mixtures, which they were able to enter and leave at will, and the level of aversion was assessed in terms of the initial withdrawal and total dwelling times in the chamber. Comparisons between the anaesthetic and air-control treatments indicated that concentrations of the agents recommended for the rapid and efficient induction of anaesthesia were associated with some degree of aversion. Carbon dioxide was by far the most aversive gas for both rats and mice, with the least aversive being halothane for rats, and halothane and enflurane for mice. With all the anaesthetics, the level of aversion increased as the concentration increased.

[Inhalation anesthesia with halogen-containing anesthetics in children]. / Ingaliatsionnaia anesteziia galogenosoderzhashchimi anestetikami u detei.

The study was carried out in 158 children aged 3-16 years operated on in an inpatient setting. The patients were divided into 3 groups with different types of induction narcosis: 1) ethrane inhalation up to 3 vol% and N2O with O2 in 1:1 ratio (56 pts); 2) fluothane up to 3.5 vol% and N2O with O2 in 2:1 ratio (87 pts), and 3) isoflurane inhalation up to 3 vol% and N2O with O2 in 1:1 ratio (15 children). Central hemodynamics, cardiointervalograms, and external respiration function were studied. Ethrane and isoflurane induction was longer (4-12 min) than fluothane induction (3-5 min). Anesthesia with ethrane and isoflurane in combination with N2O with O2 led to a less pronounced reaction of the central hemodynamics than fluothane anesthesia, which led to a decrease of the sympathic tone and increase in the activity of the parasympathetic component of the autonomic nervous system. Analyzing a vast scope of clinical material on the use of inhalation anesthetics and all the pros and contras, the authors conclude that inhalation anesthetics can be used in children.

The effects of some porphyrinogenic drugs on the brain cholinergic system.

In central nervous system, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyse acetylcholine. Diminished cholinesterase activity is known to alter several mental and psychomotor functions. The symptoms of cholinergic crisis and those observed during acute attacks of acute intermittent porphyria are very similar. The aim of this study was to investigate if there could be a link between the action of some porphyrinogenic drugs on brain and the alteration of the cholinergic system. To this end, AChE and BuChE activities were assayed in whole and different brain areas. Muscarinic acetylcholine receptor (mAChR) levels were also measured. Results obtained indicate that the porphyrinogenic drugs tested affect central cholinergic transmission. Quantification of mAChR gave quite different levels depending on the xenobiotic. Veronal administration inhibited 50% BuChE activity in whole brain, cortex and hippocampus; concomitantly cortex mAChR was 30% reduced. Acute and chronic isoflurane anaesthesia diminished BuChE activity by 70-90% in whole brain instead cerebellum and hippocampus mAChR levels were only altered by chronic enflurane anaesthesia. Differential inhibition of cholinesterases in the brain regions and their consequent effects may be of importance to the knowledge of the mechanisms of neurotoxicity of porphyrinogenic drugs.

Fresh gas flow is not the only determinant of volatile agent consumption: a multi-centre study of low-flow anaesthesia.

METHODS: Seven academic centres studied 302 patients, using desflurane, enflurane, halothane, or isoflurane using circle-systems and Dräger Julian anaesthetic machines, with fresh gas flows (V(F)) of 3, 1, and 0.5 litre min(-1). Volatile agent partial pressures in the breathing system were recorded and agent consumptions measured by weighing. RESULTS: At these flows, desflurane consumption depended on V(F). In contrast, halothane consumption was not influenced by V(F). Isoflurane and enflurane showed differences in consumption between flows of 0.5 and 3 litre min(-1). Stepwise linear regression suggested that besides V(F), other factors influenced consumption of the more soluble agents (sex, age, weight, height, altitude, and temperature). The partial pressure ratios were independent of V(F) for desflurane (end-tidal to fresh gas=0.8), but the ratios of the more soluble agents varied with V(F) (end-tidal to fresh gas=0.3-0.7). CONCLUSIONS: At V(F) that involves significant re-breathing, consumption of soluble agents depends only partially on V(F). These results can be explained using Mapleson's hydraulic analogue model.

Antagonism of inhalant and volatile anesthetic enhancement of glycine receptor function.

Recent studies suggest that alcohols, volatile anesthetics, and inhaled drugs of abuse, which enhance gamma-aminobutyric acid, type A, and glycine receptor-activated ion channel function, may share common or overlapping molecular sites of action on these receptors. To investigate this possibility, these compounds were applied singly and in combination to wild-type glycine alpha(1) receptors expressed in Xenopus laevis oocytes. Data obtained from concentration-response curves of the volatile anesthetic enflurane constructed in the presence and absence of ethanol, chloroform, or toluene were consistent with competition for a common binding pocket on these receptors. A mutant glycine receptor, insensitive to the enhancing effects of ethanol but not anesthetics or inhalants, demonstrated antagonism of anesthetic and inhalant effects on this receptor. Although ethanol (25-200 mm) had no effect on its own in this receptor, it was able to inhibit reversibly the enhancing effect of enflurane, toluene, and chloroform in a concentration-dependent manner. These data suggest the existence of overlapping molecular sites of action for ethanol, inhalants, and volatile anesthetics on glycine receptors and illustrate the feasibility of pharmacological antagonism of the effects of volatile anesthetics.

The minimum alveolar concentration of enflurane for laryngeal mask airway extubation in deeply anesthetized children.

UNLABELLED: The end-tidal anesthetic gas concentration required to prevent the anesthetized patient from coughing or moving during or immediately after the laryngeal mask airway (LMA) extubation is not known. We sought to determine the minimum alveolar concentration of enflurane required for the removal of the LMA in children. We studied 21 nonpremedicated children between 4 and 11 yr of age, ASA physical status I, undergoing procedures below the umbilicus. General anesthesia was induced with a mask by using sevoflurane, nitrous oxide, and oxygen, and the LMA was inserted. Anesthesia was maintained with enflurane, nitrous oxide, and oxygen. At the end of surgery, a predetermined end-tidal enflurane concentration was achieved, and the LMA was removed. Each concentration at which the LMA extubation was attempted was predetermined by the up-and-down method (with 0.1% as a step size). When LMA removal was accomplished without coughing, clenching teeth, or gross purposeful muscular movements during or within 1 min after removal, it was considered a successful LMA removal. Removal was considered to be unsuccessful in patients who developed breath holding or laryngospasm during or immediately after LMA removal. The minimum alveolar concentration of enflurane at which 50% of children had a successful LMA removal was found to be 1.02% (95% CL, 0.95%-1.11%), and the 95% effective dose for successful extubation was 1.14% (95% CL, 1.07%-1.66%). In conclusion, the LMA removal may be accomplished without coughing or moving at 1.02% end-tidal enflurane concentration in 50% of anesthetized children aged 4-11 yr. IMPLICATIONS: There may be fewer problems associated with the laryngeal mask airway extubation when patients are deeply anesthetized. The purpose of this study was to determine the minimum concentration of enflurane for successful removal of the laryngeal mask in children.