Widespread Inhibition of Sodium Channel-dependent Glutamate Release from Isolated Nerve Terminals by Isoflurane and Propofol

Background : Controversy persists concerning the mechanisms and role of general anesthetic inhibition of glutamate release from nerve endings. To determine the generality of this effect and to control for methodologic differences between previous studies, the authors analyzed the presynaptic effects of isoflurane and propofol on glutamate release from nerve terminals isolated from several species and brain regions.

Methods : Synaptosomes were prepared from rat, mouse, or guinea pig cerebral cortex and also from rat striatum and hippocampus. Release of endogenous glutamate evoked by depolarization with 20 [mu]m veratridine (which opens voltage-dependent Na+ channels by preventing inactivation) or by 30 mm KCl (which activates voltage-gated Ca2+ channels by membrane depolarization) was monitored using an on-line enzyme-linked fluorometric assay.

Results : Glutamate release evoked by depolarization with increased extracellular KCl was not significantly inhibited by isoflurane up to 0.7 mm (~2 minimum alveolar concentration; drug concentration for half-maximal inhibition > 1.5 mm) or propofol up to 40 [mu]m in synaptosomes prepared from rat, mouse, or guinea pig cerebral cortex, rat hippocampus, or rat striatum. Lower concentrations of isoflurane or propofol significantly inhibited veratridine-evoked glutamate release in all three species (isoflurane IC50 = 0.41-0.50 mm; propofol IC50 = 11-18 [mu]m) and rat brain regions. Inhibition of veratridine-evoked release was insensitive to the [gamma]-aminobutyric acid receptor type A antagonist bicuculline (100 [mu]m) in rat cortical synaptosomes.     

Neuroprotective Effects of Propofol in a Model of Ischemic Cortical Cell Cultures: Role of Glutamate and Its Transporters

Background: During cerebral ischemia, excess of glutamate release and dysfunction of its high affinity transport induce an accumulation of extracellular glutamate, which plays an important role in neuronal death. The authors studied the relationship among propofol neuroprotection, glutamate extracellular concentrations, and glutamate transporter activity in a model of ischemic cortical cell cultures.

Methods: Thirteen-day-old primary cortical neuronal-glial cultures were exposed to a 90-min combined oxygen-glucose deprivation (OGD) in an anaerobic chamber, followed by reoxygenation. Propofol was added only during the OGD period, and its effect was compared to that of the N-methyl-d-aspartate receptor antagonist dizocilpine (MK-801). Twenty-four hours after the injury, cell death was quantified by lactate dehydrogenase release and cell viability by reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Extracellular concentrations of glutamate in culture supernatants and glutamate uptake were performed at the end of OGD period by high-performance liquid chromatography and incorporation of l-[3H]glutamate into cells, respectively.

Results: At clinically relevant concentrations (0.05-10 [mu]m), propofol offered protection equivalent to that of MK-801. It significantly reduced lactate dehydrogenase release and increased the reduction of MTT. At the end of the ischemic injury, propofol was able to reverse the OGD-induced increase in glutamate extracellular concentrations and decrease of glutamate uptake. The inhibition of the glial GLT1 transporter by 3-methyl-glutamate did not further modify the effect of propofol on glutamate uptake, suggesting that GLT1 was not the major target of propofol.     

General Anesthetics Do Not Affect Release of the Neuropeptide Cholecystokinin from Isolated Rat Cortical Nerve Terminals

Background: General anesthetics inhibit evoked release of classic neurotransmitters. However, their actions on neuropeptide release in the central nervous system have not been well characterized.

Methods: The effects of representative intravenous and volatile anesthetics were studied on the release of sulfated cholecystokinin 8 (CCK8s), a representative excitatory neuropeptide, from isolated rat cerebrocortical nerve terminals (synaptosomes). Basal, elevated KCl depolarization-evoked and veratridine-evoked release of CCK8s from synaptosomes purified from rat cerebral cortex was evaluated at 35[degrees]C in the absence or presence of extracellular Ca2+. CCK8s released into the incubation medium was determined by enzyme-linked immunoassay after filtration.

Results: Elevation of extracellular KCl concentration (to 15-30 mm) or veratridine (10-20 [mu]m) stimulated Ca2+-dependent CCK8s release. Basal, elevated KCl- or veratridine-evoked CCK8s release was not affected significantly by propofol (12.5-50 [mu]m), pentobarbital (50 and 100 [mu]m), thiopental (20 [mu]m), etomidate (20 [mu]m), ketamine (20 [mu]m), isoflurane (0.6-0.8 mm), or halothane (0.6-0.8 mm).     

Hypothermia and Isoflurane Similarly Inhibit Glutamate Release Evoked by Chemical Anoxia in Rat Cortical Brain Slices

Background: Accumulation of the excitatory neurotransmitter glutamate in ischemic brain tissue contributes to neuronal cell death. Volatile anesthetics at clinically relevant concentrations are neuroprotective in in vivo models of brain ischemia and reduce glutamate release in vivo and in vitro, but they appear to have weaker neuroprotective effects than hypothermia. The purpose of this study was to determine whether isoflurane reduces glutamate release in hypoxic brain slices, how large this effect is compared to that of hypothermia, and if it is diminished by hyperthermia.

Methods: Glutamate released from rat cortical brain slices during chemical anoxia (100 micro Meter NaCN) was measured continuously with a fluorescence assay. The release rate was compared at three temperatures (28 degrees Celsius, 37 degrees Celsius, and 39 degrees Celsius) with and without isoflurane at concentrations equipotent to 1 minimum alveolar concentration. At the same three temperatures, glutamate release rates before and after exposure to isoflurane were compared.

Results: Isoflurane reduced glutamate release from brain slices during chemical anoxia at 37 degrees Celsius (19.6%, P < 0.01) and at 39 degrees Celsius (25.4%, P < 0.01), but not at 28 degrees Celsius. The reduction in glutamate release with hypothermia was similar to that with isoflurane. Hyperthermia (39 degrees Celsius) caused greater glutamate release under basal and anoxic conditions than normo- and hypothermia. Isoflurane caused a slight increase in basal glutamate release rates, although this effect was smaller than the increase caused by hyperthermia.     

Differential Effects of Isoflurane and Propofol on Upper Airway Dilator Muscle Activity and Breathing

Background: Anesthesia impairs upper airway integrity, but recent data suggest that low doses of some anesthetics increase upper airway dilator muscle activity, an apparent paradox. The authors sought to understand which anesthetics increase or decrease upper airway dilator muscle activity and to study the mechanisms mediating the effect.

Methods: The authors recorded genioglossus electromyogram, breathing, arterial blood pressure, and expiratory carbon dioxide in 58 spontaneously breathing rats at an estimated ED50 (median effective dose) of isoflurane or propofol. The authors further evaluated the dose-response relations of isoflurane under different study conditions: (1) normalization of mean arterial pressure, or end-expiratory carbon dioxide; (2) bilateral lesion of the Kolliker-Fuse nucleus; and (3) vagotomy. To evaluate whether the markedly lower inspiratory genioglossus activity during propofol could be recovered by increasing flow rate, a measure of respiratory drive, the authors performed an additional set of experiments during hypoxia or hypercapnia.

Results: In vagally intact rats, tonic and phasic genioglossus activity were markedly higher with isoflurane compared with propofol. Both anesthetics abolished the genioglossus negative pressure reflex. Inspiratory flow rate and anesthetic agent predicted independently phasic genioglossus activity. Isoflurane dose-dependently decreased tonic and increased phasic genioglossus activity, and increased flow rate, and its increasing effects were abolished after vagotomy. Impairment of phasic genioglossus activity during propofol anesthesia was reversed during evoked increase in respiratory drive.     

Differential Neurotoxic Effects of Propofol on Dissociated Cortical Cells and Organotypic Hippocampal Cultures

Background: Propofol is a widely used anesthetic agent for adults and children. Although extensive clinical use has demonstrated its safety, neurologic dysfunctions have been described after the use of this agent. A recent study on a model of aggregating cell cultures reported that propofol might cause irreversible lesions of [gamma]-aminobutyric acid-mediated (GABAergic) neurons when administered at a critical phase of brain development. We investigated this issue by comparing the effects of long-term propofol treatment on two models of brain cultures: dissociated neonatal cortical cell cultures and organotypic slice cultures.

Methods: Survival of GABAergic neurons in dissociated cultures of newborn rat cortex (postnatal age, 1 day) treated for 3 days with different concentrations of propofol was assessed using histologic and cytochemical methods. For hippocampal organotypic slice cultures (postnatal age, 1 and 7 days), cell survival was assessed by measuring functional and morphologic parameters: extracellular and intracellular electrophysiology, propidium staining of dying cells, and light and electron microscopy.

Results: In dissociated neonatal cell cultures, propofol induced dose-dependent lesions of GABAergic neurons and of glial cells. In contrast, no evidence for neurotoxic effects of propofol were found after long-term treatment of organotypic slice cultures. Excitatory transmission was not affected by propofol, and inhibitory transmission was still functional. Histologic preparations showed no evidence for cell degeneration or death.     

Effects of Propofol on Sodium Channel-dependent Sodium Influx and Glutamate Release in Rat Cerebrocortical Synaptosomes

Background: Previous electrophysiologic studies have implicated voltage-dependent Na+ channels as a molecular site of action for propofol. This study considered the effects of propofol on Na+ channel-mediated Na+ influx and neurotransmitter release in rat brain synaptosomes (isolated presynaptic nerve terminals).

Methods: Purified cerebrocortical synaptosomes from adult rats were used to determine the effects of propofol on Na+ influx through voltage-dependent Na+ channels (measured using22 Na+) and intracellular [Na+] (measured by ion-specific spectrofluorimetry). For comparison, the effects of propofol on synaptosomal glutamate release evoked by 4-aminopyridine (Na+ channel dependent), veratridine (Na (+) channel dependent), and KCl (Na+ channel independent) were studied using enzyme-coupled fluorimetry.

Results: Propofol inhibited veratridine-evoked22 Na+ influx (inhibitory concentration of 50% [IC50] = 46 micro Meter; 8.9 micro Meter free) and changes in intracellular [Na+] (IC50 = 13 micro Meter; 6.3 micro Meter free) in synaptosomes in a dose-dependent manner. Propofol also inhibited 4-aminopyridine-evoked (IC50 = 39 micro Meter; 19 micro Meter free) and veratridine (20 micro Meter)-evoked (IC (50) = 30 micro Meter; 14 micro Meter free), but not KCl-evoked (up to 100 micro Meter) glutamate release from synaptosomes.     

Effects of Propofol and Remifentanil on Phrenic Nerve Activity and Nociceptive Cardiovascular Responses in Rabbits

Background: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits.

Methods: Basal anesthesia and constant blood gas tensions were maintained with [alpha]-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP ([DELTA]HR, [DELTA]MAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg [middle dot] kg-1 [middle dot] min-1 (group I) and remifentanil from 0.0125 to 12.8 [mu]g [middle dot] kg-1 [middle dot] min-1 alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg [middle dot] kg-1 [middle dot] min-1 (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V).

Results: The infusion rates for 50% depression (ED50) of PNA, [DELTA]HR, and [DELTA]MAP were 0.41, 1.32, and 1.58 mg [middle dot] kg-1 [middle dot] min-1 for propofol, and 0.115, 0.125, and 1.090 [mu]g [middle dot] kg-1 [middle dot] min-1 for remifentanil, respectively. The ratios for the ED50 values of [DELTA]HR and [DELTA]MAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and [DELTA]MAP were synergistic for [DELTA]HR, they were merely additive. Remifentanil had no effect on propofol blood levels.     

Effects of Propofol or Isoflurane Anesthesia on Cardiac Conduction in Children Undergoing Radiofrequency Catheter Ablation for Tachydysrhythmias

Background: To determine suitability for ablation procedures in children, two commonly used anesthetic agents were studied: propofol and isoflurane.

Methods: Twenty patients presenting for a radiofrequency catheter ablation procedure were included and randomly assigned to two groups. A baseline electrophysiology study was performed during anesthesia with thiopental, alfentanil, nitrous oxide, and pancuronium in all patients. At the completion of the baseline electrophysiology study (EPS), 0.8-1.2% isoflurane was administered to patients in group 1 and 2 mg/kg propofol bolus plus an infusion of 150 micro gram *symbol* kg sup -1 *symbol* min sup -1 was administered to patients in group 2. Nitrous oxide and pancuronium were used throughout the procedure. After 30 min of equilibration, both groups underwent a repeat EPS. The following parameters were measured during the EPS: cycle length, atrial-His interval, His-ventricle interval, corrected sinus node recovery time, AV node effective refractory period, and atrial effective refractory period. Using paired t tests, the electrophysiologic parameters described above measured during propofol or isoflurane anesthesia were compared to those measured during baseline anesthesia. Statistical significance was accepted as P < 0.05.

Results: There was no statistically significant difference in the results obtained during baseline anesthesia when compared with those measured during propofol or isoflurane anesthesia.     

Intraoperative Modulation of Alveolar Macrophage Function during Isoflurane and Propofol Anesthesia

Background: Alveolar macrophages are a critical part of the defense against pulmonary infection. Thus the authors determined time-dependent changes in alveolar macrophage functions in patients having surgery who were anesthetized with isoflurane or propofol.

Methods: Patients anesthetized with propofol (n = 30) or isoflurane (n = 30) during orthopedic surgery were studied. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2, 4, and 6 h after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. Then phagocytosis was measured by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly.

Results: Demographic and morphometric characteristics of the patients given propofol and isoflurane were similar, as were their levels of pulmonary function and hemodynamic responses. The fraction of alveolar macrophages ingesting opsonized and unopsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease slightly but significantly greater during isoflurane anesthesia. Microbicidal function decreased progressively during anesthesia and surgery, with the decrease almost twice as great during isoflurane compared with propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic.     

Bispectral Analysis Measures Sedation and Memory Effects of Propofol, Midazolam, Isoflurane, and Alfentanil in Healthy Volunteers

Background: The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for four commonly used anesthetic drugs: propofol, midazolam, isoflurane, and alfentanil.

Methods: Seventy-two consenting volunteers were studied at four institutions. Volunteers were given either isoflurane, propofol, midazolam, or alfentanil. Each volunteer was administered a dose-ranging sequence of one of the study drugs to achieve predetermined target concentrations. A frontal montage was used for continuous recording of the EEG. At each pseudo-steady-state drug concentration, a BIS score was recorded, the participant was shown either a picture or given a word to recall, an arterial blood sample was obtained for subsequent analysis of drug concentration, and the participant was evaluated for level of sedation as determined by the responsiveness portion of the observer's assessment of the alertness/sedation scale (OAAS). An OAAS score of 2 or less was considered unconscious. The BIS (version 2.5) score was recorded in real-time and the BIS (version 3.0) was subsequently derived off-line from the recorded raw EEG data. The relation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logistic regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated.

Results: The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the responsiveness score. The BIS provided as effective correlation with responsiveness score of the OAAS as did the measured concentration for midazolam and isoflurane. None of the volunteers given alfentanil lost consciousness and thus were excluded from the pooled analysis. The pooled BIS values at which 50% and 95% of participants were unconscious were 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performance for correctly indicating probability of loss of consciousness.     

The Effect of Thiopental and Propofol on NMDA- and AMPA-mediated Glutamate Excitotoxicity

Background: Glutamate excitotoxicity has been implicated as an important cause of ischemic, anoxic, epileptic, and traumatic neuronal damage. Glutamate receptor antagonists have been shown to reduce anoxic, ischemic, and epileptic damage. The effects of thiopental and propofol on N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA)-induced neuronal damage were investigated in this study.

Methods: The Schaffer collateral pathway was stimulated, and a postsynaptic-evoked population spike was recorded from the CA1 pyramidal cell layer of rat hippocampal slices. The recovery of the population spike amplitude was an indicator of neuronal viability. The duration of NMDA (25 micro Meter) or AMPA (15 or 10 micro Meter) treatment was 10 min. Thiopental (600 micro Meter), propofol (112 micro Meter), or the vehicle was present 15 min before, during, and 10 min after the NMDA or AMPA treatment.

Results: Thiopental prolonged the time required to completely block the population spike after the addition of NMDA or AMPA. Thiopental improved the recovery of the population spike after 25 micro Meter NMDA (79% vs. 44%) and 15 micro Meter AMPA (50% vs. 15%). Propofol worsened the recovery of the population spike from NMDA-induced damage. The recovery was 8% with propofol compared with 40% with NMDA alone. Propofol did not significantly alter the AMPA-induced neuronal damage.     

皮层躯体感觉诱发电位在监测腰神经根损伤中作用的研究

目的：利用大鼠髓核突出动物模型。探索皮层躯体感觉诱发电位（CSEP）的波幅和潜伏期变化是否与神经根性疼痛有关系。方法：取大鼠自体尾部的髓核无压迫下放置在L4和L5神经根上，制成髓核突出动物模型。分别在术后3d,1,2及4周观察大鼠术侧肢体机械刺激敏感性和热刺激敏感性和热刺激敏感性的变化，并引出大鼠后肢CSEP，观察术侧肢体CSEP的变化。结果：在无明显机械压迫的情况下，大鼠腰神经根上植入自体髓核可产生痛觉过敏，CSEP波幅增高。结论：髓核自身是引起腰腿痛的重要原因，CSEP波幅的增高与神经根性疼痛有一定相关性。     

Negative and Selective Effects of Propofol on Isolated Swine Myocyte Contractile Function in Pacing-induced Congestive Heart Failure

Background: Although propofol (2-6 di-isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations.

Methods: Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micro meter/s) was examined in myocytes from five control pigs and in five pigs with pacing-induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1-6 micro gram/ml. In addition, myocyte contractility in response to beta-adrenergic receptor stimulation (isoproterenol, 10-50 nM) in the presence of propofol (3 micro gram/ml) was examined.

Results: Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end-diastolic diameter (control 3.3 +/- 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/- 3% vs. CHF 12 +/- 2%, P < 0.05). Propofol (6 micro gram/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 micro meter/s vs. 27 +/- 3 micro meter/s; P < 0.05) and CHF myocytes (29 +/- 1 micro meter/s vs. 15 +/- 1 micro meter/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 micro gram/ml). beta-adrenergic responsiveness was reduced by propofol (3 micro gram/ml) in control myocytes only.     

Propofol Prevents Peroxide-induced Inhibition of Glutamate Transport in Cultured Astrocytes

Background: Glutamate transporters located in the plasma membrane of cerebral astrocytes take up excitatory neurotransmitters from the synaptic cleft. In diseases characterized by oxidative stress, the extracellular glutamate concentration increases and contributes to neuronal death. The authors wanted to determine whether propofol defends brain cells against oxidant-induced changes in their transport of glutamate.

Methods: Primary cultures of rat cerebral astrocytes were exposed to tert-butyl hydroperoxide (1 mM) to serve as an in vitro model of oxidative stress. Astrocytes were incubated with propofol for 2 h and tert-butyl hydroperoxide was added for the final hour. Alternatively, astrocytes were incubated with tert-butyl hydroperoxide for 30 min and then with propofol for another 30 min. Control cells received drug vehicle rather than propofol. The rate of uptake of glutamate, the efflux of the nonmetabolizable analog D-aspartate, and the intracellular concentration of the endogenous antioxidant glutathione were measured.

Results: Tert-butyl hydroperoxide decreased the glutathione concentration and inhibited glutamate uptake but had a negligible effect on D-aspartate efflux. At clinically relevant concentrations, propofol did not affect the glutathione concentration but did prevent the effect of tert-butyl hydroperoxide on glutamate transport. Furthermore, the addition of propofol after tert-butyl hydroperoxide reversed the inhibition of glutamate uptake.     

神经生长因子预处理对鼠脑皮质培养细胞缺血／再灌注损伤的保护作用

目的：比较不同浓度神经生长因子（NGF）预处理离体幼鼠脑皮质培养细胞对脑缺血／再灌注（cerebral ischemia-reperfusion injury,I／R）损伤的保护作用。方法：取出生24h内的SD乳鼠脑皮质细胞,体外培养至第7日随机分为正常对照组、药物损伤组、及10、50、100ug／l神经生长因子预处理组。各预处理组分别以对应浓度的药物进行预处理,24h后除正常对照组外,各组予20μmol／L谷氨酸损伤0．5h,换正常培养液继续培养24h后进行观察。检测神经细胞存活率（MTT法）,乳酸脱氢酶（LDH）漏出率,细胞凋亡率;苏本素-伊红（HE）染色后倒置相差显微镜下观察细胞形态变化。结果：各浓度神经生长因子预处理组的细胞存活率高于药物损伤组,LDH漏出量和细胞凋亡率不同程度的低予药物损伤组;各药物预处理组细胞形态的受损程度均较药物损伤组轻。三个预处理组中以50ug／l组效果最佳。结论：不同浓度的神经生长因子提前24h预处理离体幼鼠脑皮质培养细胞对脑I／R损伤均有保护作用,其中50ug／l神经生长因子预处理效果最佳。     

异丙酚麻醉下PaCO2对SjvO2影响的年龄差异

目的研究异氟醚和异丙酚维持神经外科手术中低碳酸和高碳酸血症对颈静脉球血氧饱和度(SjvO     

The Effect of Propofol on Isolated Human Pregnant Uterine Muscle

Background: Propofol is an alternative to thiopental as an intravenous induction agent for cesarean section. Because it has relaxant effects on vascular and other smooth muscles, the authors set out to determine whether propofol has any effect on pregnant human uterine smooth muscle in an isolated preparation.

Methods: Myometrial specimens were excised from 10 parturients undergoing elective cesarean section. The muscle strips were suspended in tissue baths and isometric tension was recorded. After establishment of rhythmic contractions in the buffer solution as a control, propofol (0.5 to 10 [micro sign]g/ml) in fat emulsion was applied cumulatively to the bath. The effect of the fat emulsion at equivalent concentrations was also examined.

Results: Propofol concentrations of 2.7 x 10-6 M (0.5 [micro sign]g/ml) and 1.1 x 10-5 M (2 [micro sign]g/ml) had no significant effect on the active tension developed by muscle contraction. However, propofol at concentration of 5.5 x 10-5 M (10 [micro sign]g/ml) reduced the active tension by 45% (P < 0.02) compared with the control value. The fat emulsion had no effects on the active tension.