Propofol rather than Isoflurane Accelerates the Interstitial Fluid Drainage in the Deep Rat Brain.

Objective: Different anesthetics have distinct effects on the interstitial fluid (ISF) drainage in the extracellular space (ECS) of the superficial rat brain, while their effects on ISF drainage in the ECS of the deep rat brain still remain unknown. Herein, we attempt to investigate and compare the effects of propofol and isoflurane on ECS structure and ISF drainage in the caudate-putamen (CPu) and thalamus (Tha) of the deep rat brain. Methods: Adult Sprague-Dawley rats were anesthetized with propofol or isoflurane, respectively. Twenty-four anesthetized rats were randomly divided into the propofol-CPu, isoflurane-CPu, propofol-Tha, and isoflurane-Tha groups. Tracer-based magnetic resonance imaging (MRI) and fluorescent-labeled tracer assay were utilized to quantify ISF drainage in the deep brain. Results: The half-life of ISF in the propofol-CPu and propofol-Tha groups was shorter than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. The ECS volume fraction in the propofol-CPu and propofol-Tha groups was much higher than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. However, the ECS tortuosity in the propofol-CPu and propofol-Tha groups was much smaller than that in isoflurane-CPu and isoflurane-Tha groups, respectively. Conclusions: Our results demonstrate that propofol rather than isoflurane accelerates the ISF drainage in the deep rat brain, which provides novel insights into the selective control of ISF drainage and guides selection of anesthetic agents in different clinical settings, and unravels the mechanism of how general anesthetics function.

Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium.

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein, effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters' interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol, atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

Pancuronium enhances isoflurane anesthesia in rats via inhibition of cerebral nicotinic acetylcholine receptors.

PURPOSE: This study was conducted to elucidate the mechanism of enhancement of volatile anesthetics by neuromuscular blocking agents in rats and to consider the relevance of this enhancement to clinical anesthesia. METHODS: Male Sprague-Dawley rats were used. After confirming a movement in response to tail clamping under 1.1 % isoflurane anesthesia, response was determined when the tail clamp was applied at several points after microinjection of pancuronium into the lateral ventricle. Arousal responses to microinjection of nicotine into the lateral ventricle were assessed with or without pretreatment with intraventricular pancuronium. The intravenous 50 % effective dose (ED50) and 95 % effective dose (ED95) for neuromuscular blockade with pancuronium administered in a cumulative fashion at 1.1 % isoflurane were calculated. RESULTS: Intraventricular pancuronium dose-dependently reduced the response to tail clamping, and the dose required to show immobilization of 50 % of rats (intraventricular ED50) was 1.62 µg/kg. Pretreatment with pancuronium at 6 µg/kg significantly reduced the effect of awakening by nicotine under isoflurane anesthesia (P = 0.044). The intravenous ED50 and ED95 for neuromuscular blockade were 63 µg/kg (90 % confidence interval [CI] 52-75 µg/kg) and 133 µg/kg (90 % CI 109-158 µg/kg), respectively. The ratio of intraventricular ED50 to intravenous ED50 was 0.026. CONCLUSION: Pancuronium microinjection into the lateral ventricle dose-dependently enhances the depth of isoflurane anesthesia, which might be caused by inhibition of neuronal nicotinic acetylcholine receptor transmission in the cerebrum. Intravenous injection of pancuronium at high doses might increase the cerebrospinal concentration to a level at which an effect can be observed.

Changes in thalamo-frontal interaction under different levels of anesthesia in rats.

Anesthesia is thought to be mediated by inhibiting the integration of information between different areas of the brain. Long-range thalamo-cortical interaction plays a critical role in inducing anesthesia-related unconsciousness. However, it remains unclear how this interaction change according to anesthetic depth. In this study, we aimed to investigate how different levels of anesthesia affect thalamo-frontal interactions. Prior to the experiment, electrodes were implanted to record local field potentials (LFPs). Isoflurane (ISO) was administered and LFPs were measured in rats from four different brain areas (left frontal, right frontal, left thalamus and right thalamus) at four different anesthesia levels: awake, deep (ISO 2.5vol%), light (ISO 1vol%) and recovery. Spectral granger causality (Spectral-GC) were calculated at the measured areas in accordance with anesthetic levels. Anesthesia led to a decrease in connectivity in the thalamo-frontal direction and an increase in connectivity in the frontal-thalamic direction. The changes in thalamo-frontal functional connectivity were prominent during deep anesthesia at high frequency bands. The connection strengths between the thalamus and the frontal area changed depending on the depth of anesthesia. The relationships between anesthetic levels and thalamo-frontal activity may shed light on the neural mechanism by which different levels of anesthesia act.

Comparison of Dexmedetomidine-Ketamine with Isoflurane for Anesthesia of Chinchillas (Chinchilla lanigera).

The objective of this study was to compare isoflurane with a combination of dexmedetomidine and ketamine, administered intramuscularly, for anesthesia in chinchillas (Chinchilla lanigera). In a prospective, complete crossover study, adult chinchillas (n = 8; age, 2 to 5 y) were anesthetized with a combination of dexmedetomidine (0.015 mg/kg IM) and ketamine (4 mg/kg IM). Atipamezole (0.15 mg/kg) was injected subcutaneously 45 min after dexmedetomidine-ketamine administration. For comparison, anesthesia also was induced and maintained with isoflurane in 100% oxygen, delivered by facemask. Anesthetic and physiologic parameters were recorded during each anesthesia, including various reflexes, heart rate, respiratory rate, body temperature, and SpO2. Food intake, fecal output, and body weight were recorded daily for 6 d after each anesthetic trial. Induction time, heart rate, respiratory rate, and body temperature did not differ significantly between the 2 anesthetic protocols. Recovery times were shorter and SpO2 was higher in animals that received isoflurane delivered in 100% oxygen. Food intake and fecal output were reduced in the dexmedetomidine-ketamine group for as long as 3 d after anesthesia, whereas isoflurane had no signifcant effect on food intake or fecal output. Both anesthetic protocols provided effective anesthesia in chinchillas. However, when anesthetized with dexmedetomidine-ketamine, chinchillas received room air and became hypoxemic. Future studies are needed to evaluate the effect of oxygen supplementation on anesthetic recovery and on the recovery of food intake and fecal output in chinchillas.

Adding Emulsified Isoflurane to Cardioplegia Solution Produces Cardiac Protection in a Dog Cardiopulmonary Bypass Model.

This study investigated whether caridoplegia solution with Emulsified Isoflurane (EI) could improve cardiaoprotection in a dog CPB model of great similarity to clinical settings. Adult dogs were randomly assigned to receive one of the following cardioplegia solutions: St. Thomas with EI (group ST+EI), St. Thomas with 30% Intralipid (group ST+EL) and St. Thomas alone (group ST). The aorta was cross-clamped for two hours followed by reperfusion for another two hours, during which cardiac output was measured and dosages of positive inotropic agent to maintain normal hemodynamics were recorded. Serum level of cardiac troponin I (cTnI) and CK-MB were measured. Deletion of cardiac mitochondrial DNA was examined at the end of reperfusion. Compared with ST, ST+EI decreased the requirement of dopamine support while animals receiving ST+EI had a significantly larger cardiac output. ST+EI reduced post-CPB release of cTnI and CK-MB. Mitochondrial DNA loss was observed in only one of the tested animals from group ST+EI while it was seen in all the tested animals from group ST+EL and ST. Addition of emulsified isoflurane into cardioplegia solution protects against myocardial ischemia reperfusion injury. This protective effect might be mediated by preserving mitochondrial ultrastructure and DNA integrity.

Attenuation of High-Frequency (50-200 Hz) Thalamocortical Electroencephalographic Rhythms by Isoflurane in Rats Is More Pronounced for the Thalamus Than for the Cortex.

BACKGROUND: Thalamocortical electroencephalographic rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. We have recently shown that propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 50 to 200 Hz range and that this effect is far more pronounced for the thalamus. To determine whether similar attenuation occurs with other anesthetics, we characterized the concentration-effect relationship of the inhaled anesthetic isoflurane on the spectral power of these rhythms. METHODS: Local field potentials were recorded from the barrel cortex and ventroposteromedial thalamic nucleus in 9 chronically instrumented rats to measure spectral power in the gamma/high-gamma range (30-200 Hz). Rats were placed in an airtight chamber and isoflurane was administered at 0.75%, 1.1%, and 1.5% concentrations. Spectral power was assessed during baseline, at the 3 isoflurane concentrations after 30 minutes for equilibration, and during recovery over 4 frequency bands (30-50, 51-75, 76-125, and 126-200 Hz). Unconsciousness was defined as sustained loss of righting reflex. Multiple linear regression was used to model the change in power (after logarithmic transformation) as a function of concentration and recording site. P values were corrected for multiple comparisons. RESULTS: Unconsciousness occurred at the 1.1% concentration in all animals. Isoflurane caused a robust (P ≤ 0.008) linear concentration-dependent attenuation of cortical and thalamic power in the 30 to 200 Hz range. The concentration-effect slope for the thalamus was steeper than for the cortex in the 51 to 75 Hz (P = 0.029) and 76 to 200 Hz (P < 0.001) ranges but not for the 30 to 50 Hz range (P = 0.320). Comparison with our previously published propofol data showed that slope for cortical power was steeper with isoflurane than with propofol for all frequency bands (P = 0.033). For thalamic power, the slope differences between isoflurane and propofol were not statistically significant (0.087 ≤ P ≤ 0.599). CONCLUSIONS: Isoflurane causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30 to 200 Hz range, and this effect is more pronounced for the thalamus than for the cortex for frequencies >50 Hz. In comparison with propofol, isoflurane caused a greater attenuation in the cortex, but the effects on the thalamus were similar. Isoflurane and propofol cause common alterations of fast thalamocortical rhythms that may constitute an electrophysiologic signature of the anesthetized state.

The negative effects of chronic exposure to isoflurane on spermatogenesis via breaking the hypothalamus-pituitary-gonadal equilibrium.

This study aims to investigate the negative effects of chronic exposure to isoflurane on spermatogenesis and explore the underlying mechanisms. Sixty male rats were randomly allocated to two groups: control group, receiving no treatment, and anesthesia group, administrated exposure to isoflurane (2 ppm) for 25 consecutive days (1 h/day). The negative effects of chronic exposure to isoflurane were evaluated by analyzing the median eminence GnRH content, the relevant hormone levels, some sperm parameters and the mRNA expressions for some reproduction-related genes. Isoflurane significantly decreased the GnRH content and the serum gonadotrophin levels compared with the control group (p<0.01). Meanwhile, the mRNA expressions of GnRH in hypothalamus, GnRH receptor, luteinizing hormone (LH)-ß and follicle-stimulating hormone (FSH)-ß in pituitary, and LH receptor and FSH receptor in testes were also significantly inhibited (p<0.01). Furthermore, the mRNA expressions of androgen receptor (AR), kisspeptin encoded gene (Kiss-1) and its receptor (GPR54) in hypothalamus were significantly diminished by isoflurane (p<0.01). The results indicated that chronic exposure to isoflurane diminished the synthesis and secretion of GnRH by inhibiting the androgen-AR-Kisspeptin-GPR54 pathway and breaking the hypothalamic-pituitary-gonadal equilibrium, and therefore it could inhibit spermatogenesis.

[Isoflurane-induced malignant hyperthermia during intensive-care treatment]. / Isofluranassoziierte maligne Hyperthermie im Rahmen der Intensivtherapie.

Malignant hyperthermia (MH), an inherited myopathia varying in severity and course, is induced by halogenated anesthetic agents and depolarizing muscle relaxants. First recognized as a distinct disease entity in 1960, MH is defined as an anesthesia-related disease due to the agents by which it is triggered. Given the wide use of these preparations in prehospital emergency medicine and intensive care treatment, physicians in other disciplines may also encounter MH.

Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.

Pancuronium is a long-duration neuromuscular blocking drug (NMBD) that has been used in anesthetized rabbits at 0.1 mg/kg. However, there are limited data regarding the time course for recovery from this dose either spontaneously or with pharmacologic reversal. Here we defined the potency, onset, and recovery characteristics for the intermediate-duration NMBD cisatracurium and CW002 (a novel cysteine-inactivated molecule) in the rabbit, and test the hypothesis that these drugs may be alternatives to 0.1 mg/kg pancuronium for survival procedures. New Zealand white rabbits anesthetized with isoflurane were studied in a cross-over design. Potencies of cisatracurium and CW002 were defined as the effective dose for 95% depression of evoked muscle twitch (ED95). Responses to 3×ED95 were used to define onset (time to maximal effect), recovery index (RI; time from 25% to 75% recovery of twitch), and duration (time to complete recovery). Responses to all drugs were determined with and without reversal by neostigmine-glycopyrrolate or L-cysteine. CW002 was 4-fold more potent than was cisatracurium, but their onset, RI, and duration were similar. Pancuronium had similar onset and RI but longer duration, compared with cisatracurium and CW002. Reversal shortened the recovery index and duration for all 3 drugs. At 3×ED95, cisatracurium and CW002 had the same onset as did standard-dose pancuronium, but durations were shorter and more predictable. In addition, CW002 can be reversed without the potential side effects of cholinergic manipulation. We conclude that cisatracurium and CW002 are viable alternatives to pancuronium for survival studies in rabbits.

Intravenous pretreatment with emulsified isoflurane preconditioning protects kidneys against ischemia/reperfusion injury in rats.

BACKGROUND: Emulsified isoflurane (EIso) is a novel intravenous general anesthetic, which can provide rapid anesthetic induction and recovery. EIso preconditioning could attenuate heart, lung and liver ischemia/reperfusion (I/R) injury. We tested the hypothesis that intravenous pretreatment with EIso would protect kidneys against I/R injury by inhibiting systemic inflammatory responses and improving renal antioxidative ability. METHODS: RATS WERE RANDOMLY DIVIDED INTO THESE SIX GROUPS: sham, I/R, intralipid, 1, 2 or 4 ml/kg EIso. Rats were subjected to 45 min left renal pedicle occlusion followed by 3 h reperfusion after right nephrectomy. Rat were treated with intravenous 8% EIso with 1, 2 or 4 ml/kg, or 30% intralipid with 2 ml/kg for 30 min before ischemia, respectively. After reperfusion, renal functional parameters, serum mediator concentrations and markers of oxidative stress in kidney tissues were determined, and renal histopathological analysis were performed. RESULTS: Serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, interleukin-6, and interleukin-10 concentrations were significantly increased after renal I/R as compared to the sham group. So was renal tissue MDA content and histological scores, but renal tissue SOD activity was decreased. Additionally, severe morphological damages were observed in these study groups. In contrast, 2 or 4 ml/kg EIso reduced serum creatinine, blood urea nitrogen, cystatin c, tumor necrosis factor-α, and interleukin-6 levels, decreased renal tissue MDA content and histological scores, increased serum interleukin-10 level and tissue SOD activity as compared to the I/R, intralipid and 1 ml/kg EIso groups. Renal morphological damages were alleviated after pretreatment of 2 or 4 ml/kg EIso. CONCLUSIONS: Intravenous EIso produces preconditioning against renal I/R injury in rats, which might be mediated by attenuating inflammation and increasing antioxidation ability.

Eletroacupuntura para tratamento de hipotensão induzida por isofluorano em cavalos / Electroacupuncture treatment for isoflurane induced hypotension in horses

Objetivou-se avaliar a eficiência do tratamento da hipotensão arterial com eletroacupuntura comparativamente à dobutamina em equinos. Foram avaliados seis cavalos adultos, saudáveis, mantidos em anestesia inalatória, com isofluorano, em ventilação mecânica. Após a estabilização da anestesia, foi induzida hipotensão arterial, através do incremento da concentração do isofluorano, iniciando-se um dos tratamentos: DOB: dobutamina (1,5µg kg-1 min-1, infusão contínua intravenosa); EA: estímulo elétrico no acuponto pericárdio 6 (PC6), bilateralmente; SHAM: estímulo elétrico em ponto falso de acupuntura. Foram mensurados: frequência cardíaca (FC), pressão arterial média (PAM), temperatura retal (T), concentração final expirada de isofluorano (ETiso), variáveis hemogasométricas, concentração sérica de aspartato aminotransferase (AST) e creatina fosfoquinase (CK), tempo e qualidade da recuperação pós-anestésica. Houve incremento na PAM de 50%, 36,6% e 7,5% nos tratamentos DOB, EA e SHAM, respectivamente. Não houve diferença entre os grupos nas variáveis hemogasométricas, FC, T, ETiso, CK, AST, tempo e qualidade de recuperação pós-anestésica. Conclui-se que o tratamento com dobutamina foi mais efetivo para o tratamento da hipotensão em cavalos sob anestesia inalatória quando comparado ao estímulo elétrico do acuponto PC6 ou ponto falso de acupuntura...

This study aimed to evaluate the efficacy of electroacupuncture compared to the dobutamine treatment of hypotension in equines. Six adult horses were maintained in isoflurane anesthesia with mechanical ventilation. After anesthesia was established, the isoflurane concentration was raised until hypotension was achieved. After that the animals were treated with a constant rate of 1.5mg kg -1min-1 intravenous dobutamine (DOB), electroacupunture to pericardium 6 (PC-6) acupoint (EA) and false point treatment (SHAM). Heart rate (HH), median arterial blood pressure (MAP), rectal temperature (T), isoflurane end-tidal concentration, arterial blood gases, creatine kinase (CK), aspartate transaminase (AST), recovery time and quality of recovery were investigated. The MAP increased 50%, 36.5% and 7.5%% in DOB, EA and SHAM treatments, respectively. HH, T, arterial blood gases, CK, AST, recovery time and quality of recovery did not differ among treatments. It was concluded that the dobutamine treatment was more effective than EA and SHAM treatments for the reversion of isoflurane induced hypotension in horses...

Emulsified isoflurane enhances thermal transient receptor potential vanilloid-1 channel activation-mediated sensory/nociceptive blockade by QX-314.

BACKGROUND: QX-314 produces nociceptive blockade, facilitated by permeation through transient receptor potential vanilloid-1 (TRPV1) channels. TRPV1 channel can be activated by noxious heat and sensitized by volatile anesthetics. The authors hypothesized that emulsified isoflurane (EI) could enhance thermal TRPV1 channel activation-mediated sensory/nociceptive blockade by QX-314. METHODS: Rats were perineurally injected with QX-314 (Sigma-Aldrich Co. Ltd. Shanghai, China) alone or QX-314 combined with EI, followed by heat exposure on the injection site. The tail-flick and tail-clamping tests were used to assess sensory and nociceptive blockade, respectively; a sciatic nerve block model was used to assess motor and sensory blockade. Effects of EI on thermal activation of TRPV1 channels were evaluated on rat dorsal root ganglia neurons by whole-cell patch-clamp recordings. RESULTS: Heat exposure enhanced sensory/nociceptive blockade by QX-314 in rat tails, but not motor blockade in sciatic nerve block model. QX-314 alone or QX-314 + 42°C produced no nociceptive blockade. QX-314 + 48°C produced 100% nociceptive blockade with duration of 12.5 ± 2.0 h (mean ± SEM). By adding 2% EI, QX-314 + 42°C produced 80% nociceptive blockade with duration of 8.1 ± 1.9 h, which was similar to the effect of QX-314 + 46°C (7.7 ± 1.1 h; P = 0.781). The enhancement of heat on sensory/nociceptive blockade of QX-314 was prevented by TRPV1 channel antagonist. The temperature thresholds of TRPV1 channel activation on dorsal root ganglia neurons were significantly reduced by EI. CONCLUSIONS: Thermal activation of TRPV1 channels enhanced long-lasting sensory/nociceptive blockade by QX-314 without affecting motor blockade. The addition of EI reduced temperature thresholds for inducing long-lasting sensory/nociceptive blockade due to QX-314.

The neuroprotective effects of isoflurane preconditioning in a murine transient global cerebral ischemia-reperfusion model: the role of the Notch signaling pathway.

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia-reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic-reperfusion. However, these molecules were down-regulated at 72 h after ischemic-reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.

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).

Emulsified isoflurane postconditioning produces cardioprotection against myocardial ischemia-reperfusion injury in rats.

Emulsified isoflurane (EIso) preconditioning can induce cardioprotection. We investigated whether EIso application after ischemia protects hearts against reperfusion injury and whether it is mediated by the inhibition of apoptosis. Rats were subjected to 30-min coronary occlusion followed by 180-min reperfusion. At the onset of reperfusion, rats were intravenously administered saline (sham, control group), 30 % intralipid (IL group) or 2 ml kg(-1) EIso (EIso group) for 30 min. After reperfusion, infarct sizes, myocardial apoptosis and expression of Bcl-2, Bax and caspase-3 proteins were determined. Hemodynamic parameters were not different among groups. Compared with control and intralipid group, EIso limited infarct size, inhibited apoptosis, increased the expression of Bcl-2, decreased the expression of Bax, cleaved caspase-3, and enhanced Bcl-2/Bax ratio. EIso protects hearts against reperfusion injury when administered at the onset of reperfusion, which may be mediated by the inhibition of apoptosis via modulation of the expression of pro- and anti-apoptotic proteins.

Neuropeptide alterations in the tree shrew hypothalamus during volatile anesthesia.

Neuropeptides are critical signaling molecules, involved in the regulation of diverse physiological processes including energy metabolism, pain perception and brain cognitive state. Prolonged general anesthesia has an impact on many of these processes, but the regulation of peptides by general anesthetics is poorly understood. In this study, we present an in-depth characterization of the hypothalamic neuropeptides of the tree shrew during volatile isoflurane/nitrous oxide anesthesia administered accompanying a neurosurgical procedure. Using a predicted-peptide database and hybrid spectral analysis, we first identified 85 peptides from the tree shrew hypothalamus. Differential analysis was then performed between control and experimental group animals. The levels of 12 hypothalamic peptides were up-regulated following prolonged general anesthesia. Our study revealed for the first time that several neuropeptides, including alpha-neoendorphin and somatostatin-14, were altered during general anesthesia. Our study broadens the scope for the involvement of neuropeptides in volatile anesthesia regulation, opening the possibility for investigating the associated regulatory mechanisms.

Auditory evoked bursts in mouse visual cortex during isoflurane anesthesia.

General anesthesia is not a uniform state of the brain. Ongoing activity differs between light and deep anesthesia and cortical response properties are modulated in dependence of anesthetic dosage. We investigated how anesthesia level affects cross-modal interactions in primary sensory cortex. To examine this, we continuously measured the effects of visual and auditory stimulation during increasing and decreasing isoflurane level in the mouse visual cortex and the subiculum (from baseline at 0.7 to 2.5 vol % and reverse). Auditory evoked burst activity occurred in visual cortex after a transition during increase of anesthesia level. At the same time, auditory and visual evoked bursts occurred in the subiculum, even though the subiculum was unresponsive to both stimuli previous to the transition. This altered sensory excitability was linked to the presence of burst suppression activity in cortex, and to a regular slow burst suppression rhythm (~0.2 Hz) in the subiculum. The effect disappeared during return to light anesthesia. The results show that pseudo-heteromodal sensory burst responses can appear in brain structures as an effect of an anesthesia induced state change.

Concentration-dependent isoflurane effects on withdrawal reflexes in pigs and the role of the stimulation paradigm.

In this prospective two-phase experimental trial, 10 pigs were anaesthetized twice with isoflurane only. In the first phase, the individual minimum alveolar concentration (MAC) was determined and in the second phase the effects on withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6% to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were used to evoke withdrawal reflexes which were recorded and quantified by electromyography. Recruitment curves for reflex amplitude for increasing stimulation intensities and isoflurane concentrations were constructed. Isoflurane MAC was 1.9 ± 0.3%. Reflexes evoked by repeated stimulation were suppressed at isoflurane concentrations significantly higher than those which suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10 and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able to abolish reflex activity evoked by repeated stimulations in all pigs. Single stimulation reflexes were suppressed at significantly lower concentrations than repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated stimuli, respectively). Reflex amplitude was significantly correlated with isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC. The findings indicate that the level at which isoflurane suppresses withdrawal reflexes is dependent on the stimulation paradigm (single vs. repeated electrical stimulation), and there is limited value in expressing reflex withdrawal suppression in terms of MAC as purposeful and reflex movements are independently affected by isoflurane in individual animals.

Effects of intraperitoneal administration of gabapentin on the minimum alveolar concentration of isoflurane in adult male rats.

Gabapentin has been used to treat a variety of conditions in both human and veterinary medicine, including seizures, neuropathies and chronic pain. However, little information is known about the effects of gabapentin on the minimum alveolar concentration (MAC) of volatile anaesthetics. In this study, we investigated the effect of intraperitoneal administration of gabapentin on isoflurane MAC in adult male rats and hypothesized that gabapentin would decrease MAC in a dose-dependent manner. Using a standard MAC study protocol, we compared five treatment groups (G) receiving 0 (G(0)), 30 (G(30)), 100 (G(100)), 300 (G(300)) and 1000 (G(1000)) mg/kg gabapentin intraperitoneally and compared post-drug MAC values among groups and with corresponding baseline MAC values determined in each group prior to drug testing. The average baseline isoflurane MAC value was 1.45 ± 0.17%, which did not differ significantly between groups (1.47 ± 0.23% [G(30)], 1.46 ± 0.23% [G(100)], 1.48 ± 0.18% [G(300)] and 1.42 ± 0.2% [G(1000)]). In the G(300) and G(1000) groups, the isoflurane MAC value decreased significantly by 19% and 18%, respectively, from corresponding baseline values (P< 0.05, when compared with G(0)). Linear regression analysis revealed a negative correlation between blood gabapentin concentration and percent change in MAC (R(2) = 0.43; P< 0.05) but not dose. In conclusion, high-dose intraperitoneal gabapentin decreased isoflurane MAC. However, the effect was small and not dose-dependent, and is unlikely to be clinically significant.