RESUMEN
Building on their known ability to influence sleep and arousal, Li and colleagues show that modulating the activity of glutamatergic pedunculopontine tegmental neurones also alters sevoflurane-induced hypnosis. This finding adds support for the shared sleep-anaesthesia circuit hypothesis. However, the expanding recognition of many neuronal clusters capable of modulating anaesthetic hypnosis raises the question of how disparate and anatomically distant sites ultimately interact to coordinate global changes in the state of the brain. Understanding how these individual sites work in concert to disrupt cognition and behaviour is the next challenge for anaesthetic mechanisms research.
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Anestésicos por Inhalación , Hipnosis , Humanos , Sevoflurano/farmacología , Sueño/fisiología , Anestésicos por Inhalación/farmacología , EncéfaloRESUMEN
BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep-wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R-expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAcD1R neurons and the NAcD1R -VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1-receptor-expressing neurons located in the nucleus accumbens (NAcD1R neurons) and the NAcD1R -VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAcD1R neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAcD1R neurons and the NAcD1R -VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically-encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAcD1R neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAcD1R neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAcD1R -VP pathway exerted opposite effects. CONCLUSION: The NAcD1R -VP pathway serves as a crucial downstream pathway of NAcD1R neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells.
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Anestesia , Prosencéfalo Basal , Ratones , Animales , Núcleo Accumbens/metabolismo , Dopamina/metabolismo , Sevoflurano/farmacología , Prosencéfalo Basal/metabolismo , Calcio/metabolismo , Receptores de Dopamina D1/metabolismo , Neuronas Dopaminérgicas/metabolismo , Neurotransmisores/metabolismo , Neurotransmisores/farmacología , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.
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Anestesia , Anestésicos por Inhalación , Delirio del Despertar , Éteres Metílicos , Humanos , Niño , Sevoflurano/farmacología , Sevoflurano/uso terapéutico , Sufentanilo , Remifentanilo , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Anestésicos por Inhalación/farmacología , Anestésicos por Inhalación/uso terapéutico , Éteres Metílicos/uso terapéutico , Anestesia GeneralRESUMEN
BACKGROUND: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. METHODS: Rabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. RESULTS: Both γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs. mCherry-clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus-stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression. CONCLUSIONS: In mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia.
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Anestesia , Núcleos Septales , Animales , Estado de Conciencia , Femenino , Masculino , Ratones , Vías Nerviosas , Sevoflurano/farmacología , TálamoRESUMEN
BACKGROUND: Many neuroactive steroids induce sedation/hypnosis by potentiating γ-aminobutyric acid (GABAA) currents. However, we previously demonstrated that an endogenous neuroactive steroid epipregnanolone [(3ß,5ß)-3-hydroxypregnan-20-one] (EpiP) exerts potent peripheral analgesia and blocks T-type calcium currents while sparing GABAA currents in rat sensory neurons. This study seeks to investigate the behavioral effects elicited by systemic administration of EpiP and to characterize its use as an adjuvant agent to commonly used general anesthetics (GAs). METHODS: Here, we utilized electroencephalographic (EEG) recordings to characterize thalamocortical oscillations, as well as behavioral assessment and mouse genetics with wild-type (WT) and different knockout (KO) models of T-channel isoforms to investigate potential sedative/hypnotic and immobilizing properties of EpiP. RESULTS: Consistent with increased oscillations in slower EEG frequencies, EpiP induced an hypnotic state in WT mice when injected alone intra-peritoneally (i.p.) and effectively facilitated anesthetic effects of isoflurane (ISO) and sevoflurane (SEVO). The CaV3.1 (Cacna1g) KO mice demonstrated decreased sensitivity to EpiP-induced hypnosis when compared to WT mice, whereas no significant difference was noted between CaV3.2 (Cacna1h), CaV3.3 (Cacna1i) and WT mice. Finally, when compared to WT mice, onset of EpiP-induced hypnosis was delayed in CaV3.2 KO mice but not in CaV3.1 and CaV3.3 KO mice. CONCLUSION: We posit that EpiP may have an important role as novel hypnotic and/or adjuvant to volatile anesthetic agents. We speculate that distinct hypnotic effects of EpiP across all three T-channel isoforms is due to their differential expression in thalamocortical circuitry.
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Canales de Calcio Tipo T/efectos de los fármacos , Hipnóticos y Sedantes/farmacología , Pregnanolona/farmacología , Adyuvantes Anestésicos/farmacología , Anestésicos por Inhalación/farmacología , Animales , Conducta Animal/efectos de los fármacos , Canales de Calcio Tipo T/genética , Electroencefalografía/efectos de los fármacos , Isoflurano/farmacología , Isomerismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sevoflurano/farmacologíaRESUMEN
BACKGROUND: Breast cancer (BC) is common cancer in female globally. Sevoflurane (SEV) has been reported to inhibit the metastasis of multiple cancers, including glioma, colorectal cancer, and hepatocellular carcinoma. However, the role of SEV in the metastasis of BC cells remains poorly understood. METHODS: Transwell migration and invasion assays were performed to detect the migration and invasion of BC cells. Western blot assay was carried out to measure epithelial-mesenchymal transition (EMT)-related proteins in BC cells, including E-cadherin, N-cadherin, and fibronectin. Quantitative real-time polymerase chain reaction was conducted to determine the enrichment of miR-139-5p and ADP-ribosylation factor 6 (ARF6) in BC tissues and cells. The protein expression of ARF6 in BC tissues and cells was measured by western blot assay. The target of miR-139-5p was predicted by starBase software, and the target relationship between miR-139-5p and ARF6 in BC cells was confirmed by dual-luciferase reporter assay. RESULTS: SEV suppressed the migration, invasion, and EMT of BC cells, especially in the high-concentration SEV group. The level of miR-139-5p was lower in BC tissues and cells than that in paired normal tissues and normal mammary epithelial cells MCF-10A. MiR-139-5p was upregulated in BC cells treated with SEV. ARF6 was upregulated in BC tissues and cells compared with that in corresponding normal tissues and normal mammary epithelial cells MCF-10A. SEV reduced the mRNA and protein expression of ARF6 in BC cells. The accumulation of ARF6 or the interference of miR-139-5p reversed the suppressive effects of SEV treatment on the migration, invasion, and EMT of BC cells. MiR-139-5p bound to ARF6 and inversely modulated the level of ARF6 in BC cells. The transfection of si-ARF6 attenuated the promoting effects of miR-139-5p depletion on the migration, invasion, and EMT of BC cells treated with SEV. CONCLUSIONS: SEV suppressed the migration, invasion, and EMT of BC cells through downregulating the abundance of ARF6 by upregulating miR-139-5p. The miR-139-5p/ARF6 axis might be a promising target for the treatment of BC.
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Anestésicos por Inhalación/farmacología , Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Sevoflurano/farmacología , Factor 6 de Ribosilación del ADP , Factores de Ribosilacion-ADP/metabolismo , Evaluación Preclínica de Medicamentos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , MicroARNs/metabolismoRESUMEN
Phosphorus-31 nuclear-spin entanglements within Ca9(PO4)6 molecules (Posner molecules) have been proposed to be central for neural processing. However, this has yet to be proven experimentally. Relatedly, increasing calcium ion concentration in the cerebrospinal fluid has been proposed to enhance consciousness by accelerating Posner molecules' creation. A dependence on calcium isotope is also expected. Here we test these predictions experimentally by measuring the loss of righting reflex ED50 for mice to sevoflurane - an increase in loss of righting reflex ED50 indicates a higher level of consciousness and vice versa. Our mice's findings demonstrate that intracerebroventricular injection of EGTA enhances the sevoflurane-induced loss of righting reflex ED50 while injecting calcium-40 chloride or calcium-43 chloride causes an opposite effect. Further, the identical effects of calcium-40 and calcium-43 indicate an absence of calcium isotope dependence. Here, our findings disprove conventional proposals that calcium ion concentration correlates with consciousness.
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Anestesia , Fosfatos de Calcio/química , Estado de Conciencia/fisiología , Fósforo/química , Teoría Cuántica , Anestésicos por Inhalación/farmacología , Animales , Conducta Animal/fisiología , Isótopos de Calcio , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Biológicos , Sevoflurano/farmacologíaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Sevoflurane is the most widely used volatile anaesthetic in clinical practice. It exhibits a hypnotic (unconsciousness) effect and causes a loss of reaction to noxious stimuli (immobility). However, to date, the mechanism of action of sevoflurane is poorly understood. In this study, we explored the effects of genetic variations on sevoflurane-induced hypnosis. METHODS: Sixty-six SNPs in 18 candidate genes were genotyped using MALDI-TOF MassARRAY in a discovery cohort containing 161 patients administered sevoflurane. Significant polymorphisms were assessed in a validation cohort containing 265 patients. RESULTS AND DISCUSSION: Three polymorphisms (GRIN1 rs28681971, rs79901440 and CHRNA7 rs72713539) were significantly associated with the time to loss of consciousness in patients treated with sevoflurane in the discovery cohort; among them, GRIN1 rs28681971 showed a significant association even after false discovery rate (FDR) correction (pFDR = 0.039). Following the validation analysis, GRIN1 rs28681971 and rs79901440 showed statistical efficacy (pFDR = 0.027, 0.034). Combined assessments and meta-analysis of the results of the two cohorts indicated that the C carriers of rs28681971 and T carriers of rs79901440 in GRIN1 require a longer time to achieve unconsciousness. WHAT IS NEW AND CONCLUSION: These findings suggest that GRIN1 polymorphisms are associated with sevoflurane-induced unconsciousness. Thus, the genotypes of GRIN1 may serve as novel and meaningful biomarkers for sevoflurane-induced unconsciousness.
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Anestésicos por Inhalación/farmacología , Proteínas del Tejido Nervioso/genética , Receptores de N-Metil-D-Aspartato/genética , Sevoflurano/farmacología , Adulto , Anestésicos por Inhalación/administración & dosificación , Estudios de Cohortes , Variación Genética , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Sevoflurano/administración & dosificación , Factores de TiempoRESUMEN
Background: Monochromatic blue light (MBL), with a wavelength between 400-490 nm, can regulate non-image-forming (NIF) functions of light in the central nervous system. The suprachiasmatic nucleus (SCN) in the brain is involved in the arousal-promoting response to blue light in mice. Animal and human studies showed that the responsiveness of the brain to visual stimuli is partly preserved under general anesthesia. Therefore, this study aimed to investigate whether MBL promotes arousal from sevoflurane anesthesia via activation of the SCN in mice. Methods: The induction and emergence time of sevoflurane anesthesia under MBL (460 nm and 800 lux) exposure was measured. Cortical electroencephalograms (EEGs) were recorded and the burst-suppression ratio (BSR) was calculated under MBL during sevoflurane anesthesia. The EEGs and local field potential (LFP) recordings with or without locally electrolytic ablated bilateral SCN were used to further explore the role of SCN in the arousal-promoting effect of MBL under sevoflurane anesthesia. Immunofluorescent staining of c-Fos was conducted to reveal the possible downstream mechanism of SCN activation. Results: Unlike the lack of effect on the induction time, MBL shortened the emergence time and the EEG recordings showed cortical arousal during the recovery period. MBL resulted in a significant decrease in BSR and a marked increase in EEG power at all frequency bands except for the spindle band during 2.5% sevoflurane anesthesia. MBL exposure under sevoflurane anesthesia enhances the neuronal activity of the SCN. These responses to MBL were abolished in SCN lesioned (SCNx) mice. MBL evoked a high level of c-Fos expression in the prefrontal cortex (PFC) and lateral hypothalamus (LH) compared to polychromatic white light (PWL) under sevoflurane anesthesia, while it exerted no effect on c-Fos expression in the ventrolateral preoptic area (VLPO) and locus coeruleus (LC) c-Fos expression. Conclusions: MBL promotes behavioral and electroencephalographic arousal from sevoflurane anesthesia via the activation of the SCN and its associated downstream wake-related nuclei. The clinical implications of this study warrant further study.
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Anestésicos por Inhalación/farmacología , Nivel de Alerta/efectos de la radiación , Hipotálamo/efectos de la radiación , Luz , Neuronas/efectos de la radiación , Corteza Prefrontal/efectos de la radiación , Sevoflurano/farmacología , Núcleo Supraquiasmático/efectos de la radiación , Anestesia , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/efectos de la radiación , Electroencefalografía , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ratones , Neuronas/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Proteínas Proto-Oncogénicas c-fos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-fos/efectos de la radiación , Reflejo de Enderezamiento/efectos de los fármacos , Reflejo de Enderezamiento/efectos de la radiación , Núcleo Supraquiasmático/citología , Núcleo Supraquiasmático/efectos de los fármacos , Núcleo Supraquiasmático/metabolismoRESUMEN
Extended general anesthesia early in life is neurotoxic in multiple species. However, little is known about the temporal progression of neurodegeneration after general anesthesia. It is also unknown if a reduction in natural cell death, or an increase in cell creation, occurs as a form of compensation after perinatal anesthesia exposure. The goal of this study was to evaluate markers of neurodegeneration and cellular division at 2, 24, or 72 h after sevoflurane (Sevo) exposure (6 h) in fully oxygenated postnatal day (PND) 7 rats. Neurodegeneration was observed in areas throughout the forebrain, while the largest changes (fold increase above vehicle) were observed in areas associated with either the primary olfactory learning pathways or the basal ganglia. These regions included the indusium griseum (IG, 25-fold), the posterior dorso medial hippocampal CA1 (17-fold), bed nucleus of the stria terminalis (Bed Nuclei STM, 5-fold), the shell of the nucleus accumbens (Acb, 5-fold), caudate/putamen (CPu, 5-fold), globus pallidus (GP, 9-fold) and associated thalamic (11-fold) and cortical regions (5-fold). Sevo neurodegeneration was minimal or undetectable in the ventral tegmentum, substantia nigra, and most of the hypothalamus and frontal cortex. In most brain regions where neurodegeneration was increased 2 h post Sevo exposure, the levels returned to <4-fold above control levels by 24 h. However, in the IG, CA1, GP, anterior thalamus, medial preoptic nucleus of the hypothalamus (MPO), anterior hypothalamic area (AHP), and the amygdaloid nuclei, neurodegeneration at 24 h was double or more than that at 2 h post exposure. Anesthesia exposure causes either a prolonged period of neurodegeneration in certain brain regions, or a distinct secondary degenerative event occurs after the initial insult. Moreover, regions most sensitive to Sevo neurodegeneration did not necessarily coincide with areas of new cell birth, and new cell birth was not consistently affected by Sevo. The profile of anesthesia related neurotoxicity changes with time, and multiple mechanisms of toxicity may exist in a time-dependent fashion.
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Amígdala del Cerebelo/metabolismo , Ganglios Basales/metabolismo , Hipocampo/metabolismo , Sevoflurano/farmacología , Animales , Sustancia Gris/metabolismo , Ratas Sprague-Dawley , Tálamo/metabolismoRESUMEN
BACKGROUND: Cardiac power output (CPO), derived from the product of cardiac output and mean aortic pressure, is an important yet underexploited parameter for hemodynamic monitoring of critically ill patients in the intensive-care unit (ICU). The conductance catheter-derived pressure-volume loop area reflects left ventricular stroke work (LV SW). Dividing LV SW by time, a measure of LV SW min- 1 is obtained sharing the same unit as CPO (W). We aimed to validate CPO as a marker of LV SW min- 1 under various inotropic states. METHODS: We retrospectively analysed data obtained from experimental studies of the hemodynamic impact of mild hypothermia and hyperthermia on acute heart failure. Fifty-nine anaesthetized and mechanically ventilated closed-chest Landrace pigs (68 ± 1 kg) were instrumented with Swan-Ganz and LV pressure-volume catheters. Data were obtained at body temperatures of 33.0 °C, 38.0 °C and 40.5 °C; before and after: resuscitation, myocardial infarction, endotoxemia, sevoflurane-induced myocardial depression and beta-adrenergic stimulation. We plotted LVSW min- 1 against CPO by linear regression analysis, as well as against the following classical indices of LV function and work: LV ejection fraction (LV EF), rate-pressure product (RPP), triple product (TP), LV maximum pressure (LVPmax) and maximal rate of rise of LVP (LV dP/dtmax). RESULTS: CPO showed the best correlation with LV SW min- 1 (r2 = 0.89; p < 0.05) while LV EF did not correlate at all (r2 = 0.01; p = 0.259). Further parameters correlated moderately with LV SW min- 1 (LVPmax r2 = 0.47, RPP r2 = 0.67; and TP r2 = 0.54). LV dP/dtmax correlated worst with LV SW min- 1 (r2 = 0.28). CONCLUSION: CPO reflects external cardiac work over a wide range of inotropic states. These data further support the use of CPO to monitor inotropic interventions in the ICU.
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Insuficiencia Cardíaca/fisiopatología , Infarto del Miocardio/fisiopatología , Volumen Sistólico , Fibrilación Ventricular/fisiopatología , Función Ventricular Izquierda , Presión Ventricular , Agonistas Adrenérgicos beta/farmacología , Animales , Modelos Animales de Enfermedad , Dobutamina/farmacología , Endotoxemia/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hipertermia Inducida , Hipotermia Inducida , Infarto del Miocardio/diagnóstico , Resucitación , Sevoflurano/farmacología , Volumen Sistólico/efectos de los fármacos , Sus scrofa , Factores de Tiempo , Fibrilación Ventricular/diagnóstico , Fibrilación Ventricular/terapia , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular/efectos de los fármacosRESUMEN
Despite the widespread use in clinical practice, little research has been done on mechanisms of sedation. In particular, little is known about the changes in the information processing of external stimuli in sedation. The aim of this study was to investigate the changes of event-related potential (ERP) in auditory passive oddball paradigm when the sedation was induced by sevoflurane inhalation. Electroencephalography (EEG) measurements were obtained for each subject using 32-channel EEG recording devices. Sevoflurane was administered at an initial concentration of 0.8 vol% to induce sedative state. Auditory stimulation based on the passive oddball paradigm was delivered to the subject via an earphone before and after sevoflurane administration. After ERP was extracted from the measured EEG, the topographic distribution of ERP, the temporal changes of ERP in each channel, and the statistical difference in ERP between awake and sedation were analyzed. In the awake state, P300 was observed at 320-360 ms latency, and P300 was concentrated in the frontal and central area. P300 amplitude was significantly decreased in sedation compared to awake. Sevoflurane-induced sedation caused a decrease in P300 amplitude. This result may reflect the weakening of the cognitive function governing attentional process and stimuli discrimination during sedation.
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Estimulación Acústica , Potenciales Relacionados con Evento P300/efectos de los fármacos , Potenciales Evocados/efectos de los fármacos , Sevoflurano/farmacología , Estimulación Acústica/métodos , Adulto , Atención/efectos de los fármacos , Cognición/efectos de los fármacos , Electroencefalografía/métodos , Potenciales Relacionados con Evento P300/fisiología , Potenciales Evocados/fisiología , Potenciales Evocados Auditivos/efectos de los fármacos , Potenciales Evocados Auditivos/fisiología , Femenino , Humanos , Masculino , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Reperfusion ventricular arrhythmia (RA) associated with hypothermic ischaemic storage is increasingly recognized as a substantial contributor to adverse consequences after heart transplantation. Ischemia- or hypothermia-induced gap junction (GJ) remodelling is closely linked to RA. Reducing GJ remodelling contributes to RA attenuation and is important in heart transplantation. However, sevoflurane has an antiarrhythmic effect associated with the connexin 43 (Cx43) protein that has not yet been fully established. METHODS: Hearts were divided into two groups according to a random number table: all hearts were arrested by an infusion of histidine-tryptophan-ketoglutarate (HTK) solution (4 °C) followed by (1) storage in HTK solution (4 °C) alone for 6 h (n = 8, Control group) or (2) storage in HTK solution supplemented with sevoflurane (2.5%) (4 °C) for 6 h (n = 8, Sevo-HTK group). First, the total Cx43 level and the phosphorylation of Cx43 at Ser368 (Cx43-pS368) were assessed by Western blotting, and the distribution of Cx43 was assessed by immunohistochemistry. Second, programmed electrical stimulation (PES) and monophasic action potential (MAP) recording were used to analyse the MAP duration (MAPD), conduction velocity (CV) and transmural repolarization dispersion (TDR). In addition, haematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-dUTP nick end labelling (TUNEL) staining were individually used to investigate the degree of myocardial pathological damage and cell apoptosis. Finally, bipolar electrograms were used to record the graft re-beating time and monitor RA during reperfusion for 15 to 30 min. RESULTS: Sevo-HTK solution relatively increased the total Cx43 (P < 0.01) and Cx43-pS368 (P < 0.01) levels and prevented Cx43 redistribution (P < 0.05) and CV slowing (P < 0.001) but did not change TDR (P > 0.05). Additionally, the Cx43-pS368/total Cx43 ratio (P>0.05) was similar in the two groups. However, with Sevo-HTK solution, the graft re-beating times were shortened, myocardial pathological damage was ameliorated, and the number of apoptotic cells was markedly decreased. CONCLUSION: The reduction in hypothermia and ischaemia-induced reperfusion arrhythmias by the addition of sevoflurane to HTK solution may be related to the phosphorylation of Cx43 at serine 368.
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Antiarrítmicos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Isquemia Miocárdica/tratamiento farmacológico , Sevoflurano/farmacología , Animales , Arritmias Cardíacas/fisiopatología , Conexina 43/metabolismo , Modelos Animales de Enfermedad , Uniones Comunicantes/efectos de los fármacos , Uniones Comunicantes/metabolismo , Glucosa/administración & dosificación , Hipotermia/complicaciones , Manitol/administración & dosificación , Ratones , Daño por Reperfusión Miocárdica/prevención & control , Fosforilación/efectos de los fármacos , Cloruro de Potasio/administración & dosificación , Procaína/administración & dosificación , Remodelación Ventricular/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVES: In this study, we aimed to investigate the effects of sevoflurane, desflurane and propofol maintenances on serum levels of selenium, copper, zinc, iron, malondialdehyde, and glutathion peroxidase measurements, and antioxidant capacity. METHODS: 60 patients scheduled for unilateral lower extremity surgery which would be performed with tourniquet under general anesthesia were divided into three groups. Blood samples were collected to determine the baseline serum levels of selenium, copper, zinc, iron, malondialdehyde and glutathion peroxidase. Anesthesia was induced using 2-2.5 mg kg-1 propofol, 1 mg kg-1 lidocaine and 0.6 mg kg-1 rocuronium. In the maintenance of anesthesia, under carrier gas of 50:50% O2:N2O 4 L min-1, 1 MAC sevoflorane was administered to Group S and 1 MAC desflurane to Group D; and under carrier gas of 50:50% O2:air 4 L min-1 6 mg kg h-1 propofol and 1 µg kg h-1 fentanyl infusion were administered to Group P. At postoperative blood specimens were collected again. RESULTS: It was observed that only in Group S and P, levels of MDA decreased at postoperative 48th hour; levels of glutathion peroxidase increased in comparison to the baseline values. Selenium levels decreased in Group S and Group P, zinc levels decreased in Group P, and iron levels decreased in all three groups, and copper levels did not change in any groups in the postoperative period. CONCLUSION: According to the markers of malondialdehyde and glutathion peroxidase, it was concluded that maintenance of general anesthesia using propofol and sevoflurane activated the antioxidant system against oxidative stress and using desflurane had no effects on oxidative stress and antioxidant system. .
JUSTIFICATIVA E OBJETIVOS: Investigar os efeitos da manutenção de sevoflurano, desflurano e propofol sobre nos níveis séricos de selênio, cobre, zinco, ferro e malondialdeído, as mensurações de glutationa peroxidase e a capacidade antioxidante. MÉTODOS: Foram alocados em três grupos 60 pacientes agendados para cirurgia unilateral de membros inferiores, feita com torniquete sob anestesia geral. Amostras de sangue foram coletadas para determinar os níveis séricos basais de selênio, cobre, zinco, ferro, malondialdeído e glutationa peroxidase. A anestesia foi induzida com 2-2,5 mg kg-1 de propofol, 1 mg kg-1 de lidocaína e 0,6 mg kg-1 de rocurônio. Na manutenção da anestesia, sob gás de transporte de 50% O2 e 50% N2O (4 L min-1), sevoflurano a 1 CAM foi administrado ao Grupo S e desflurano a 1 CAM ao Grupo D e, sob gás de transporte em mistura de 50% O2 e 50% ar (4 L min-1), 6 mg kg h-1 de propofol e 1 mg kg h-1 de fentanil foram administrados ao Grupo P. No pós-operatório, amostras de sangue foram novamente coletadas. RESULTADOS: Apenas nos grupos S e P os níveis de MDA diminuíram em 48 horas de pós-operatório; os níveis de glutationa peroxidase aumentaram em comparação com os valores basais. Os níveis de selênio diminuíram no Grupo S e no Grupo P, os níveis de zinco diminuíram no Grupo P, os níveis de ferro diminuíram em todos os grupos e não houve alteração nos níveis de cobre em nenhum grupo no período pós-operatório. CONCLUSÃO: De acordo com os marcadores de malondialdeído e glutationa peroxidase, concluímos que a manutenção da anestesia geral com propofol e sevoflurano ativou o sistema antioxidante contra o estresse oxidativo e o uso de desflurano não teve efeitos sobre o estresse oxidativo e o sistema antioxidante. .
JUSTIFICACIÓN Y OBJETIVOS: Investigar los efectos del mantenimiento de sevoflurano, desflurano y propofol sobre los niveles séricos de selenio, cobre, cinc, hierro y malondialdehído, las medidas de glutatión peroxidasa y la capacidad antioxidante. MÉTODOS: Fueron ubicados en 3 grupos 60 pacientes programados para cirugía unilateral de miembros inferiores, realizada con torniquete bajo anestesia general. Fueron recogidas muestras de sangre para determinar los niveles séricos basales de selenio, cobre, cinc, hierro, malondialdehído y glutatión peroxidasa. La anestesia fue inducida con 2-2,5 mg/kg-1 de propofol, 1 mg/kg-1 de lidocaína y 0,6 mg/kg-1 de rocuronio. En el mantenimiento de la anestesia, bajo gas portador de 50% de O2 y 50% de N2O (4 L/min-1), sevoflurano a 1 CAM fue administrado al grupo S; y desflurano a 1 CAM al grupo D y bajo gas portador en mezcla de 50% O2 y 50% aire (4 L/min-1), 6 mg/kg/h-1 de propofol y 1 µg/kg/h-1 de fentanilo fueron administrados al grupo P. En el postoperatorio se recogieron de nuevo muestras de sangre. RESULTADOS: Solamente en los grupos S y P los niveles de malondialdehído disminuyeron en las 48 h del postoperatorio; los niveles de glutatión peroxidasa aumentaron en comparación con los valores basales. Los niveles de selenio disminuyeron en el grupo S y en el grupo P, los niveles de cinc disminuyeron en el grupo P, los de hierro disminuyeron en todos los grupos y no hubo alteración en los niveles de cobre en ningún grupo en el período postoperatorio. CONCLUSIÓN: De acuerdo con los marcadores de malondialdehído y glutatión peroxidasa, llegamos a la conclusión de que el mantenimiento de la anestesia general con propofol y sevoflurano activó el sistema antioxidante contra el estrés oxidativo y el uso de desflurano no tuvo efectos sobre el estrés oxidativo y el sistema antioxidante. .