RESUMO
Cardiac contractile dysfunction (CD) is a multifactorial syndrome caused by different acute or progressive diseases which hamper assessing the role of the underlying mechanisms characterizing a defined pathological condition. Mathematical modeling can help to understand the processes involved in CD and analyze their relative impact in the overall response. The aim of this study was thus to use a myocyte-based multiscale model of the circulatory system to simulate the effects of halothane, a volatile anesthetic which at high doses elicits significant acute CD both in isolated myocytes and intact animals. Ventricular chambers built using a human myocyte model were incorporated into a whole circulatory system represented by resistances and capacitances. Halothane-induced decreased sarco(endo)plasmic reticulum Ca2+ (SERCA2a) reuptake pump, transient outward K+ (Ito), Na+-Ca2+ exchanger (INCX) and L-type Ca2+ channel (ICaL) currents, together with ryanodine receptor (RyR2) increased open probability (Po) and reduced myofilament Ca2+ sensitivity, reproduced equivalent decreased action potential duration at 90% repolarization and intracellular Ca2+ concentration at the myocyte level reported in the literature. In the whole circulatory system, model reduction in mean arterial pressure, cardiac output and regional wall thickening fraction was similar to experimental results in open-chest sheep subjected to acute halothane overdose. Effective model performance indicates that the model structure could be used to study other changes in myocyte targets eliciting CD.
Assuntos
Cardiopatias/fisiopatologia , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Miócitos Cardíacos/fisiologia , Anestésicos Inalatórios/farmacologia , Animais , Modelos Animais de Doenças , Halotano/farmacologia , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , OvinosRESUMO
This paper analyses some aspects of the trajectory of the Argentinian physician and sociologist Juan César García (1932-1984) in the field of Latin American Social Medicine. Three dimensions constituting his basic orientations are highlighted: the elaboration of systematic and reflective social thought; a critical attitude in questioning teaching and professional practices; a commitment to the institutionalization and dissemination of health knowledge.
O artigo analisa aspectos da trajetória de Juan César García (1932-1984), médico e sociólogo argentino, no campo da medicina social latino-americana. Destaca três dimensões que constituem as suas orientações básicas no campo da saúde: a elaboração de um pensamento sobre o social, sistemático e reflexivo; uma atitude crítica na problematização do ensino e das práticas profissionais; um compromisso com a institucionalização e divulgação do saber sanitário.
Assuntos
Animais , Anestésicos Gerais/farmacologia , Luciferases de Vaga-Lume/antagonistas & inibidores , Anisotropia , Sítios de Ligação , Fenômenos Biofísicos , Biofísica , Cristalografia por Raios X , Álcoois Graxos/farmacologia , Halotano/farmacologia , Técnicas In Vitro , Luciferases de Vaga-Lume/química , Modelos Moleculares , Conformação Proteica , Estrutura Terciária de Proteína , TermodinâmicaRESUMO
GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter. The accumulation of [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 µM, respectively. TTX (blocker of voltage-dependent Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an intracellular Ca(2+) chelator) did not interfere with the accumulation of [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane-induced increase in the accumulation of GABA by 57 and 63 %, respectively. Incubation of brain cortical slices at low temperature (17 °C), a condition that inhibits GAT function and reduces GABA release through reverse transport, reduced the sevoflurane- and halothane-induced increase in the accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at normal temperature (37 °C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce GABA release through reverse transport, abolished the sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect of sevoflurane and halothane did not involve glial transporters because ß-alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the anesthetics. In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter. Therefore, volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors.
Assuntos
Anestésicos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Ácido gama-Aminobutírico/metabolismo , Anestésicos/administração & dosagem , Animais , Cálcio/farmacologia , Temperatura Baixa , Halotano/administração & dosagem , Halotano/farmacologia , Éteres Metílicos/administração & dosagem , Éteres Metílicos/farmacologia , Ácidos Nipecóticos/farmacologia , Ouabaína/farmacologia , Ratos , Sevoflurano , Tetrodotoxina/toxicidade , Trítio/metabolismo , Volatilização , beta-Alanina/farmacologiaRESUMO
In this study we used barium currents through voltage gated L-type calcium channels (recorded in freshly isolated cells with a conventional patch-clamp technique) to elucidate the cellular action mechanism for volatile anesthetics. It was found that halothane and isoflurane inhibited (dose-dependently and voltage independently) Ba2+ currents through voltage gated Ca2+ channels. Half maximal inhibitions occurred at 0.64 ± 0.07 mM and 0.86 ± 0.1 mM. The Hill slope value was 2 for both volatile anesthetics, suggesting the presence of more than one interaction site. Current inhibition by volatile anesthetics was prominent over the whole voltage range without changes in the peak of the current voltage relationship. Intracellular infusion of the GDPßS (100 µM) together with staurosporine (200 nM) did not prevent the inhibitory effect of volatile anesthetics. Unlike pharmacological Ca2+ channel blockers, volatile anesthetics blocked Ca2+ channel currents at resting membrane potentials. In other words, halothane and isoflurane induced an 'initial block'. After the first 4-7 control pulses, the cells were left unstimulated and anesthetics were applied. The first depolarization after the pause evoked a Ca2+ channel current whose amplitude was reduced to 41 ± 3.4% and to 57 ± 4.2% of control values. In an analysis of the steady-state inactivation curve for voltage dependence, volatile anesthetics induced a negative shift of the 50% inactivation of the calcium channels. By contrast, the steepness factor characterizing the voltage sensitivity of the channels was unaffected. Unitary L-type Ca2+ channels blockade occurred under cell-attached configuration, suggesting a possible action of volatile anesthetics from within the intracellular space or from the part of the channel inside the lipid bilayer.
Assuntos
Anestésicos Inalatórios/farmacologia , Aorta/citologia , Canais de Cálcio Tipo L/metabolismo , Ativação do Canal Iônico/efeitos dos fármacos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/metabolismo , Proteína Quinase C/metabolismo , Anestésicos Inalatórios/química , Animais , Bário/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Separação Celular , Proteínas de Ligação ao GTP/metabolismo , Halotano/farmacologia , Isoflurano/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , VolatilizaçãoRESUMO
The effects of continuous rate infusion of lidocaine or amiodarone on hemodynamic and arrhythmias induced by epinephrine in dogs anesthetized with halothane were evaluated. Thirty dogs were distributed into three groups: amiodarone group (AG), lidocaine group (LG), or control group (CG). Anesthesia was induced with etomidate and maintained with halothane. Thirty minutes later a bolus and continuous rate infusion (CRI) of amiodarone in AG, lidocaine in LG and NaCl at 0.9% in CG was administered. After 10 minutes, arrhythmias were induced by epinephrine CRI at 0.0001mg/kg/minute, which was increased in 0.0001mg/kg/minute every ten minutes, until 0.0003mg/kg/minute. The measurements were performed 30 minutes after the induction of anesthesia (T0), 10 minutes after beginning the drug CRIs (T1), 10 minutes after beginning epinephrine administration (T2) and 10 minutes after increasing epinephrine CRI (T3 and T4). In CG, at T3 heart rate (HR) was greater than in LG, while at T4, HR in GC was higher than in LG and AG. In LG and CG, from T2, central venous pressure (CVP), cardiac index (CI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), mean pulmonary arterial pressure (mPAP) increased. In AG, SAP, DAP and MAP it decreased from T1 to T3. The ventricular ectopic beats (VEB) were lower in AG. Amiodarone has better antiarrhythmogenic effects, although it was also associated with hypotension.
Avaliaram-se os efeitos da infusão contínua de lidocaína ou amiodarona sobre a hemodinâmica e as arritmias induzidas pela epinefrina em cães anestesiados com halotano. Trinta animais foram distribuídos em três grupos: grupo amiodarona (GA), grupo lidocaína (GL) ou grupo-controle (GC). A anestesia foi induzida com etomidato e mantida com halotano. Trinta minutos após, foram administrados bolus e infusão contínua (CRI) de amiodarona no GA, de lidocaína no GL e de NaCl a 0,9% no GC. Após 10 minutos, iniciou-se a CRI de epinefrina (0,0001mg/kg/minuto), aumentando-se 0,0001mg/kg/minuto a cada 10 minutos até 0,0003mg/kg/minuto. As mensurações foram realizadas 30 minutos após a indução anestésica (T0), 10 minutos após a CRI dos fármacos (T1), 10 minutos após a administração de epinefrina (T2) e a cada 10 minutos após o incremento na CRI de epinefrina (T3 e T4). A frequência cardíaca (FC) foi maior no GC que no GL em T3 e maior em GC que nos demais grupos em T4. A partir de T2, houve aumento na pressão venosa central (PVC), no índice cardíaco (IC), nas pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e na pressão média da artéria pulmonar (PAPm) no GL e no GC. No GA, PAS, PAD e PAM diminuíram de T1 a T3. Os batimentos ventriculares ectópicos (BVE) foram menores no GA. Amiodarona possui melhores efeitos antiarrítmicos, apesar de também estar associada com hipotensão.
Assuntos
Animais , Cães , Anestesia/veterinária , Hipotensão , Halotano/farmacologia , Hemodinâmica/fisiologia , Cães/classificaçãoRESUMO
The effects of continuous rate infusion of lidocaine or amiodarone on hemodynamic and arrhythmias induced by epinephrine in dogs anesthetized with halothane were evaluated. Thirty dogs were distributed into three groups: amiodarone group (AG), lidocaine group (LG), or control group (CG). Anesthesia was induced with etomidate and maintained with halothane. Thirty minutes later a bolus and continuous rate infusion (CRI) of amiodarone in AG, lidocaine in LG and NaCl at 0.9% in CG was administered. After 10 minutes, arrhythmias were induced by epinephrine CRI at 0.0001mg/kg/minute, which was increased in 0.0001mg/kg/minute every ten minutes, until 0.0003mg/kg/minute. The measurements were performed 30 minutes after the induction of anesthesia (T0), 10 minutes after beginning the drug CRIs (T1), 10 minutes after beginning epinephrine administration (T2) and 10 minutes after increasing epinephrine CRI (T3 and T4). In CG, at T3 heart rate (HR) was greater than in LG, while at T4, HR in GC was higher than in LG and AG. In LG and CG, from T2, central venous pressure (CVP), cardiac index (CI), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), mean pulmonary arterial pressure (mPAP) increased. In AG, SAP, DAP and MAP it decreased from T1 to T3. The ventricular ectopic beats (VEB) were lower in AG. Amiodarone has better antiarrhythmogenic effects, although it was also associated with hypotension.(AU)
Avaliaram-se os efeitos da infusão contínua de lidocaína ou amiodarona sobre a hemodinâmica e as arritmias induzidas pela epinefrina em cães anestesiados com halotano. Trinta animais foram distribuídos em três grupos: grupo amiodarona (GA), grupo lidocaína (GL) ou grupo-controle (GC). A anestesia foi induzida com etomidato e mantida com halotano. Trinta minutos após, foram administrados bolus e infusão contínua (CRI) de amiodarona no GA, de lidocaína no GL e de NaCl a 0,9% no GC. Após 10 minutos, iniciou-se a CRI de epinefrina (0,0001mg/kg/minuto), aumentando-se 0,0001mg/kg/minuto a cada 10 minutos até 0,0003mg/kg/minuto. As mensurações foram realizadas 30 minutos após a indução anestésica (T0), 10 minutos após a CRI dos fármacos (T1), 10 minutos após a administração de epinefrina (T2) e a cada 10 minutos após o incremento na CRI de epinefrina (T3 e T4). A frequência cardíaca (FC) foi maior no GC que no GL em T3 e maior em GC que nos demais grupos em T4. A partir de T2, houve aumento na pressão venosa central (PVC), no índice cardíaco (IC), nas pressões arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e na pressão média da artéria pulmonar (PAPm) no GL e no GC. No GA, PAS, PAD e PAM diminuíram de T1 a T3. Os batimentos ventriculares ectópicos (BVE) foram menores no GA. Amiodarona possui melhores efeitos antiarrítmicos, apesar de também estar associada com hipotensão.(AU)
Assuntos
Animais , Cães , Hipotensão , Halotano/farmacologia , Anestesia/veterinária , Hemodinâmica/fisiologia , Cães/classificaçãoRESUMO
JUSTIFICATIVA E OBJETIVOS: A lesão hepática pós-anestesia inalatória ainda é controversa. Estudos sugerem que agentes inalatórios geram uma resposta imune que pode provocar lesões hepáticas. O objetivo deste estudo é analisar o efeito dos anestésicos inalatórios halotano e sevoflurano no fígado de ratos submetidos à hipóxia e à reperfusão. MÉTODO: Foram utilizados 30 ratos Wistar pré-tratados com fenobarbital 0,1 por cento por cinco dias, com suspensão da medicação 24 horas antes do experimento, a fim de provocar a lesão hepática. Os animais foram distribuídos em cinco grupos com seis ratos cada. O Grupo C foi o de controle, sem qualquer tipo de tratamento; o Grupo F foi aquele no qual se induziu lesão hepática com fenobarbital; o Grupo Hipóxia foi exposto a 14 por cento de oxigênio (O2); o Grupo H recebeu halotano 1 por cento e 14 por cento de O2; e o Grupo S recebeu sevoflurano 2 por cento e 14 por cento de O2. Contadas 24 horas após a exposição dos gases, realizaram-se coletas de sangue para avaliação de transaminases (AST e ALT) e de amostras de fígado para avaliação histológica. Foram usados os testes de Análise de Variância não paramétrica de Kruskal-Wallis e, para comparação de médias, os testes de Newman-Keuls. RESULTADOS: A atividade enzimática revelou que os valores de média amostral de AST (280,33 para halotano, 181 para sevoflurano) e ALT (235 para halotano e 48,33 para sevoflurano) não indicaram diferença estatística significativa; os grupos testados apresentaram valores elevados. O sevoflurano, quando comparado com o halotano à microscopia óptica, apresentou índices menores de alteração morfológica, com p = 0,045 para esteatose, p = 0,0075 para infiltrado inflamatório e p = 0,0074 para necrose. CONCLUSÕES: O Grupo sevoflurano, quando comparado ao Grupo halotano, não apresentou lesão no parênquima hepático quando avaliado por microscopia óptica.
BACKGROUND AND OBJECTIVES: Hepatic injury after inhalational anesthesia is controversial. Studies have suggested that inhalational agents generate an immune response that can provoke hepatic injury. The objective of this study was to analyze the effects of the inhalational agents halothane and sevoflurane on the liver of rats submitted to hypoxia and reperfusion. METHODS: Thirty Wistar rats, pretreated with 0.1 percent phenobarbital for 5 days, with discontinuation of the drug 24 hours before the experiment to cause hepatic injury, were used. Animals were distributed in five groups of six rats each. The control group (C) did not receive any treatment; in the F group, phenobarbital was used to induce hepatic injury; the Hypoxia group was submitted to 14 percent oxygen (O2); the H group received 1 percent halothane and 14 percent O2; and the S group received 2 percent sevoflurane and 14 percent O2. Twenty-four hours after exposure to the gases, blood samples were collected to evaluate transaminases (AST and ALT), and liver samples were collected for histological evaluation. Kruskal-Wallis Analysis of Variance and the Newman-Keuls test were used. RESULTS: Enzymatic activity mean values of AST (280.33, for halothane, 181, for sevoflurane) and ALT (235 for halothane, and 48.33, for sevoflurane) did not show significant differences, and all groups showed elevated values. Compared to halothane on optical microscopy, sevoflurane had lower indices of morphologic changes with p = 0.045, for steatosis, p = 0.0075, for inflammatory infiltrate, and p = 0.0074, for necrosis. CONCLUSIONS: Compared to the halothane group, sevoflurane did not show injuries of the liver parenchyma on optical microscopy.
JUSTIFICATIVA Y OBJETIVOS: La lesión hepática postanestesia inhalatoria todavía es algo controversial. Algunos estudios sugieren que los agentes inhalatorios generan una respuesta inmune que puede provocar lesiones hepáticas. El objetivo de este estudio fue analizar el efecto de los anestésicos inhalatorios halotano y sevoflurano en el hígado de ratones que fueron sometidos a la hipoxia y a la reperfusión. MÉTODO: Fueron utilizados 30 ratones Wistar tratados previamente con fenobarbital al 0,1 por ciento durante cinco días, con suspensión de la medicación 24 horas antes del experimento para provocar la lesión hepática. Los animales fueron distribuidos en cinco grupos con seis ratones cada uno. El grupo C fue el de control, sin ningún tipo de tratamiento; el grupo F fue aquel en el cual se indujo la lesión hepática con fenobarbital; el grupo Hipoxia se expuso a un 14 por ciento de oxígeno (O2); el grupo H recibió halotano al 1 por ciento y al 14 por ciento de O2; y el grupo S recibió sevoflurano al 2 por ciento y al 14 por ciento de O2. Contadas 24 horas después de la exposición de los gases, se realizó la recolección de sangre para la evaluación de las transaminasas (AST y ALT), y de las muestras de hígado para la evaluación histológica. Fueron usados los test de Análisis de Variancia no paramétrica de Kruskal-Wallis, y para la comparación de los promedios se usaron los test de Newman-Keuls. RESULTADOS: La actividad enzimática arrojó valores de promedio de muestra de AST (280,33 para halotano, 181 para sevoflurano y ALT 235 para halotano y 48,33 para sevoflurano), que no indicaron diferencia estadística significativa: los grupos testados presentaron valores elevados. El sevoflurano, cuando fue comparado con el halotano a la microscopía óptica, presentó índices menores de alteración morfológica, con p = 0,045 para esteatosis, p = 0,0075 para infiltrado inflamatorio y p = 0,0074 para necrosis. CONCLUSIONES: El grupo sevoflurano, cuando se comparó con el grupo h...
Assuntos
Animais , Ratos , Anestésicos Inalatórios/farmacologia , Modelos Animais de Doenças , Halotano/farmacologia , Hepatopatias , Ratos WistarRESUMO
PURPOSE: To investigate anesthesia recovery and hemodynamic status in patients under thiopental infusion or halothane maintenance anesthesia undergoing ocular surgery. METHODS: Fifty-nine voluntary patients undergoing ocular surgery in Farabi hospital were allocated to one of two maintenance anesthesia groups: inhaled halothane, 0.8 to 1 per cent, (group I, n=37) and thiopental infusion, 10 to 12 mg/kg/hour, (group II, n=22). Hemodynamic parameters were recorded at the time of patient entrance to the operation room and at the 1, 2, 5, 10, 15, 20, 25, 30, 35, and 40 minutes following anesthesia. Anesthesia recovery variables were also compared between the two groups. RESULTS: In group I, arterial blood pressure at 10 to 40 min and heart rate at 1 and 25 min after the administration of anesthetics were significantly lower when compared with group II (W ²= 25.10, p= 0.005). Arterial oxygen saturation was similar in the two groups over the whole points of time. The time intervals between the end of surgery and beginning of the first body movements and respiratory efforts were significantly longer in group received halothane (p<0.001). CONCLUSION: Continuous infusion of thiopental can be applied effectively and safely for maintenance of anesthesia. In comparison with halothane, it is associated with lower changes of intraoperative hemodynamics and faster anesthesia recovery.
Assuntos
Anestésicos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Halotano/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Oxigênio/sangue , Tiopental/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Período de Recuperação da Anestesia , Anestésicos/farmacologia , Feminino , Halotano/farmacologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Estudos Prospectivos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Tiopental/farmacologia , Fatores de Tempo , Adulto JovemRESUMO
Astrocytes sense, integrate, and respond to stimuli generated by neurons or neural injury; this response involves gap junction (GJ) communication. Neuronal vulnerability to injury increased when cocultures of astrocytes and neurons were exposed to GJ inhibitors. However, GJ uncoupling could limit the extension of a lesion. We investigated a possible link between GJ communication and S100B secretion. S100B is a calcium-binding protein of 21 kDa that is predominantly expressed and secreted by astrocytes, which has trophic paracrine activity on neurite growth, glial proliferation, and neuronal survival. GJ inhibitors were analyzed in isolated astrocytes in primary cultures from hippocampus, acute hippocampal slices, and C6 glioma cells, which were used as a negative control. Our data indicate that GJ blocking stimulates S100B secretion in astrocyte cultures and acute hippocampal slices. Different assays were used to confirm cell integrity during exposure to GJ inhibitors. S100B secretion was observed with different types of GJ inhibitors; the resulting event was dependent on time, the nature of the inhibitor, its putative molecular target of GJ blocking, and/or the cell preparation used. Only carbenoxolone induced a fast and persistent increase in S100B secretion in both preparations. Endothelin-1 increased S100B secretion in astrocyte cultures at 1 hr, but a decrease was observed at 6 hr or in acute hippocampal slices. Physiologically, a local GJ closure associated with release of S100B in injury conditions favors the idea of a common mechanism available to limit the extension of lesion and increase the chances of cell survival.
Assuntos
Astrócitos/fisiologia , Junções Comunicantes/metabolismo , Hipocampo/fisiologia , Fatores de Crescimento Neural/metabolismo , Proteínas S100/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Carbenoxolona/análogos & derivados , Carbenoxolona/farmacologia , Linhagem Celular Tumoral , Fármacos do Sistema Nervoso Central/farmacologia , Endotelina-1/metabolismo , Ácido Flufenâmico/farmacologia , Junções Comunicantes/efeitos dos fármacos , Ácido Glicirrízico/farmacologia , Halotano/farmacologia , Hipocampo/efeitos dos fármacos , Humanos , Técnicas In Vitro , Octanóis/farmacologia , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100 , Fatores de TempoRESUMO
The serotonergic system may play a role during general anesthesia but the effect of the volatile anesthetic halothane on the release of serotonin (5-HT) is not fully understood. Rat brain cortical slices were labeled with [3H]5-HT to investigate the effects of halothane on the release of this neurotransmitter from the central nervous system. Halothane induced an increase on the release of [3H]5-HT that was dependent on incubation time and anesthetic concentration (0.006, 0.012, 0.024, 0.036, 0.048 and 0.072 mM). This effect was independent of extracellular calcium and was not affected by tetrodotoxin (blocker of voltage dependent Na+ channels). In contrast, the halothane-evoked [3H]5-HT release was reduced by BAPTA-AM, a membrane-permeable BAPTA analog that chelates intracellular Ca2+. The anesthetic-induced [3H]5-HT release depends on the ryanodine-sensitive intracellular calcium store since it was blocked by dantrolene and azumolene (inhibitors of the calcium-release through ryanodine receptors) but was not affected by aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-triphosphate receptor. The [3H]5-HT release induced by halothane comes mainly from the vesicular pool since it was reduced in about 70% by reserpine, a blocker of vesicular monoamine transporter. The halothane-evoked release of [3H]5-HT release is reduced by fluoxetine, an inhibitor of 5-HT uptake, and the volatile agent also decreased the uptake of [3H]5-HT into rat brain cortical slices. Moreover, a decrease on halothane-induced release of [3H]5-HT was also observed when the brain cortical slices were incubated at low temperature, which is known to interfere with the carrier-mediated release of the neurotransmitter. Ouabain, a Na+/K+ ATPase pump inhibitor, which induces 5-HT release through reverse transport, also decreased [3H]5-HT release induced by halothane, confirming the involvement of a carrier-mediated release of the neurotransmitter in the presence of halothane. In conclusion, these data suggest that halothane induces vesicular and carrier-mediated release of [3H]5-HT in rat brain cortical slices.