1.Effect of etomidate on the reuniens neuronal activity.
Yulong WANG ; Tingting XUE ; Yongquan CHEN
Journal of Central South University(Medical Sciences) 2021;46(1):39-46
OBJECTIVES:
To explore the effect of etomidate on the neuronal activity of ventral thalamic reuniens nucleus and the underlying mechanisms.
METHODS:
Whole-cell patch clamp method was used to explore the effect of etomidate on the activity of ventral thalamic reuniens neurons in the acute brain slices obtained from 4-5 weeks old C57BL/6J mice. The electrophysiological characteristics of ventral thalamic reuniens neurons were recorded in the current clamp mode, and then the effects of etomidate (0.5, 2.0, 8.0 μmol/L etomidate groups) and intralipid (intralipid group) on the discharge frequency and membrane potential of ventral thalamic reuniens neurons were recorded. During the experiment, the ventral thalamic reuniens neuron firing rates (RNFRs) were recorded as F
RESULTS:
In the intralipid group, there was no significant difference among the F
CONCLUSIONS
Etomidate can inhibit the activity of ventral thalamic reuniens neurons in concentration-dependent manner, and which is reversible. Etomidate with sub-anesthetic concentration inhibits the activity of ventral thalamic reuniens neurons via targeting the GABA
Animals
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Etomidate/pharmacology*
;
Mice
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Mice, Inbred C57BL
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Neurons
;
Patch-Clamp Techniques
;
Receptors, GABA-A
2.Effect of stress on myocardial apoptosis in ischemic preconditioning in rabbit hearts.
Huashan XU ; Shengxi CHEN ; Wanjun LUO ; Khan Mohammed FIROJ
Journal of Central South University(Medical Sciences) 2014;39(5):477-482
OBJECTIVE:
To determine the influence of stress on myocardial apoptosis in ischemic preconditioning group (IPC).
METHODS:
Twenty-four Japanese white rabbits were randomly divided into 4 groups (n=6): an etomidate group (the Etom group) of depressed stress established by intravenous etomidate, an IPC group, an ischemic reperfusion group (the IR group) and a methylprednisolone group (the MP group). Myocardial apoptosis was examined by DNA-laddering, in situ nick-end labeling (TUNEL) and Hoechst dyeing.
RESULTS:
The DNA ladder increased in the Etom group. The percentage of apoptosis by TUNEL method was 1.7%±0.2% in the IPC group, 2.3%±0.8% in the MP group, 3.8%±1.3% in the IR group and 3.0%±0.4% in the Etom group. Hoechst dying was 4.1%±0.9% in the IPC group, 3.5%±0.4% in the MP group, 6.2%±1.6% in the IR group and 7.6%±0.4% in the Etom group. There was significant difference between the IPC group and the Etom group or IR group, and also between the MP group and the IR group.
CONCLUSION
A depressed stress response impairs the inhibition on myocardial apoptosis in ischemic preconditioning. Methylprednisolone may inhibit myocardial apoptosis.
Animals
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Apoptosis
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Etomidate
;
pharmacology
;
Heart
;
drug effects
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Ischemic Preconditioning
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Ischemic Preconditioning, Myocardial
;
Methylprednisolone
;
pharmacology
;
Myocardium
;
pathology
;
Rabbits
3.Effects of propofol, etomidate and ethanol on GPCR mRNA expression in Daphnia pulex .
Anmin HU ; Changhong DONG ; Yunxia ZUO ; Guohua LI
Journal of Biomedical Engineering 2014;31(4):827-832
The mechanisms of general anesthesia, which was introduced about 170 years ago, remain poorly under- stood. Even less well understood are the effects of general anesthesia on the human body. Recently we identified 18 G-protein coupled receptor (GPCR) genes of Daphnia pulex, an invertebrate model organism. Phylogenetic analysis identified these genes to be the homologs of the human γ-aminobutyric acid, type B (GABAB) receptor, metabotropic glutamate receptors (mGluR), adrenergic receptor, serotonin (5-HT) receptor, dopamine receptor and muscarinic acetylcholine receptor (mAChR). Using reverse transcription and quantitative PCR techniques, we systematically measured the effects of propofol, etomidate and ethanol on these 18 GPCR mRNA expressions in Daphnia pulex.
Animals
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Daphnia
;
drug effects
;
metabolism
;
Ethanol
;
pharmacology
;
Etomidate
;
pharmacology
;
Phylogeny
;
Propofol
;
pharmacology
;
RNA, Messenger
;
genetics
;
metabolism
;
Receptors, GABA-B
;
genetics
;
metabolism
4.Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons.
Hong-yu TAN ; Li-na SUN ; Xiao-liang WANG ; Tie-hu YE
Chinese Medical Journal 2010;123(6):702-706
BACKGROUNDPrevious studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current (I(K(DR))) and transient outward potassium current (I(K(A))) in acutely dissociated rat hippocampal pyramidal neurons.
METHODSSingle rat hippocampal pyramidal neurons from male Wistar rats of - 10 days were acutely dissociated by enzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification. Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student's paired two-tail t test was used for data analysis.
RESULTSAt the concentration of 100 micromol/L, etomidate significantly inhibited I(K(DR)) by 49.2% at +40 mV when depolarized from -110 mV (P < 0.01, n = 8), while did not affect I(K(A)) (n = 8, P > 0.05). The IC(50) value of etomidate for blocking I(K(DR)) was calculated as 5.4 micromol/L, with a Hill slope of 2.45. At the presence of 10 micromol/L etomidate, the V1/2 of activation curve was shifted from (17.3 +/- 1.5) mV to (10.7 +/- 2.9) mV (n = 8, P < 0.05), the V1/2 of inactivation curve was shifted from (-18.3 +/- 2.2) mV to (-45.3 +/- 9.4) mV (n = 8, P < 0.05). Etomidate 10 micromol/L shifted both the activation curve and inactivation curve of I(K(DR)) to negative potential, but mainly affected the inactivation kinetics.
CONCLUSIONSEtomidate potently inhibited I(K(DR)) but not I(K(A)) in rat hippocampal pyramidal neurons. I(K(DR)) was inhibited by etomidate in a concentration-dependent manner, while I(K(A)) remained unaffected.
Anesthetics, Intravenous ; pharmacology ; Animals ; Delayed Rectifier Potassium Channels ; drug effects ; physiology ; Etomidate ; pharmacology ; Male ; Potassium Channels ; drug effects ; physiology ; Pyramidal Cells ; drug effects ; physiology ; Rats ; Rats, Wistar
5.Peri-intubation hemodynamic changes during low dose fentanyl, remifentanil and sufentanil combined with etomidate for anesthetic induction.
Chinese Medical Journal 2009;122(19):2330-2334
BACKGROUNDAlthough etomidate is associated with very few cardiovascular side-effects and minimal histamine release, it has a less inhibitory effect on the pharyngolaryngeal reflex. Hence, blunting the responses to endotracheal intubation is more dependent of opioids for etomidate-based anesthetic induction. This prospective, randomized, double-blinded study was designed to investigate the effects of low dose remifentanil, fentanyl or sufentanil on etomidate induction with respect to hemodynamics, conscious level changes and drug consumption.
METHODSNinety unpremedicated and normotensive patients with American Society of Anesthesiologists (ASA) physical status I or II undergoing elective major abdominal surgery were randomly assigned in a double blinded fashion to each of the three groups: groups F, R and S. A bolus dose of fentanyl 1 microg/kg, sufentanil 0.1 microg/kg or remifentanil 1 microg/kg was given over 60 seconds in groups F, S and R, respectively. In each instance this loading dose was followed by a continuous infusion (0.1, 0.01 or 0.1 microg x kg(-1) x min(-1) of fentanyl, sufentanil or remifentanil, respectively). After 5 minutes from start of opioid infusion, etomidate was titrated at a rate of 20 mg/min to a decrease in bispectral index (BIS) to 50. The time from administration of etomidate to loss of eyelash reflex or to a decrease in BIS to 50 was recorded. The blood pressure and heart rate were also recorded at different five time points. The average maximum percent changes of systolic blood pressure (|maximal or minimal measuring value-baseline|/baseline x 100%) were calculated.
RESULTSThe time and the dosage of etomidate necessary to loss consciousness were greater in group F ((70.0 +/- 15.6) seconds; (0.35 +/- 0.05) mg/kg) than in groups S ((52.3 +/- 15.9) seconds; (0.26 +/- 0.06) mg/kg) and R ((56.2 +/- 20.2) seconds; (0.27 +/- 0.07) mg/kg) (P < 0.01). The three groups took similar time and amount of etomidate to achieve an adequate depth anesthesia (BIS = 50). The average maximum changes of systolic blood pressure were significantly different among the three groups: F, (25 +/- 6)% vs R, (13 +/- 4)% or S, (12 +/- 5)% (P < 0.001). The endotracheal intubation caused marked increases in blood pressure and heart rate in groups F and S, but not in group R, respectively (P < 0.01). The great hemodynamic changes occurred more frequently in group F than in groups R and S (P < 0.01). The incidence of heart rate decreases of more than 30% of the baselines after induction was higher in group R compared with groups F and S (P < 0.01).
CONCLUSIONSIn normotensive and unpremedicated young adult patients receiving etomidate induction, low dose remifentanil or sufentanil significantly reduced the time and the amount of etomidate taken to loss unconsciousness compared with low dose fentanyl, but similar time interval and doses of etomidate were required to acquire adequate depth of anesthesia (BIS = 50) for these three opioids. Remifentanil was more effective in blunting the cardiovascular responses to endotracheal intubation, nevertheless, accompanying significant lower heart rate after induction.
Adult ; Aged ; Anesthesia ; Anesthetics, Intravenous ; pharmacology ; Double-Blind Method ; Electroencephalography ; Etomidate ; pharmacology ; Female ; Fentanyl ; pharmacology ; Hemodynamics ; drug effects ; Humans ; Intubation, Intratracheal ; Male ; Middle Aged ; Piperidines ; pharmacology ; Prospective Studies ; Sufentanil ; pharmacology
6.Neonatal Propofol and Etomidate Exposure Enhance Inhibitory Synaptic Transmission in Hippocampal Cornus Ammonis 1 Pyramidal Neurons.
Jia-Qiang ZHANG ; Wan-Ying XU ; Chang-Qing XU
Chinese Medical Journal 2016;129(22):2714-2724
BACKGROUNDPropofol and etomidate are the most important intravenous general anesthetics in the current clinical use and that mediate gamma-aminobutyric acid's (GABAergic) synaptic transmission. However, their long-term effects on GABAergic synaptic transmission induced by neonatal propofol or etomidate exposure remain unclear. We investigated the long-term GABAergic neurotransmission alterations, following neonatal propofol and etomidate administration.
METHODSSprague-Dawley rat pups at postnatal days 4-6 were underwent 6-h-long propofol-induced or 5-h-long etomidate-induced anesthesia. We performed whole-cell patch-clamp recording from pyramidal cells in the cornus ammonis 1 area of acute hippocampal slices of postnatal 80-90 days. Spontaneous and miniature inhibitory GABAergic currents (spontaneous inhibitory postsynaptic currents [sIPSCs] and miniature inhibitory postsynaptic currents [mIPSCs]) and their kinetic characters were measured. The glutamatergic tonic effect on inhibitory transmission and the effect of bumetanide on neonatal propofol exposure were also examined.
RESULTSNeonatal propofol exposure significantly increased the frequency of mIPSCs (from 1.87 ± 0.35 Hz to 3.43 ± 0.51 Hz, P< 0.05) and did not affect the amplitude of mIPSCs and sIPSCs. Both propofol and etomidate slowed the decay time of mIPSCs kinetics (168.39 ± 27.91 ms and 267.02 ± 100.08 ms vs. 68.18 ± 12.43 ms; P< 0.05). Bumetanide significantly blocked the frequency increase and reversed the kinetic alteration of mIPSCs induced by neonatal propofol exposure (3.01 ± 0.45 Hz and 94.30 ± 32.56 ms).
CONCLUSIONSNeonatal propofol and etomidate exposure has long-term effects on inhibitory GABAergic transmission. Propofol might act at pre- and post-synaptic GABA receptor A (GABAA) receptors within GABAergic synapses and impairs the glutamatergic tonic input to GABAergic synapses; etomidate might act at the postsynaptic site.
Animals ; CA1 Region, Hippocampal ; drug effects ; metabolism ; Electrophysiology ; Etomidate ; pharmacology ; Hippocampus ; drug effects ; metabolism ; Neurons ; drug effects ; metabolism ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; metabolism ; Synaptic Transmission ; drug effects ; gamma-Aminobutyric Acid ; metabolism
7.Effects of etomidate on local synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
Zhen LI ; Ceng LUO ; Yan-Yan SUN ; Jun CHEN
Acta Physiologica Sinica 2004;56(3):413-418
By using blind spinal slice whole-cell patch-clamp technique, we observed the influence of etomidate (ET) on synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord. Male adult Sprague-Dawley rats (7~8 weeks old) were anaesthetized with urethane (1.2 g/kg, i.p.), and then lumbosacral laminectomy was performed. The lumbosacral spinal cord (L1~S3) was removed and placed in preoxygenated Krebs solution at 1~3 degrees C. After cutting all of the ventral and dorsal roots, the pia-arachnoid membrane was removed. The spinal cord was mounted on a vibrating microslicer and then a 500 microm thick transverse slice was cut. The slice was placed on a nylon mesh in the recording chamber, and then perfused at a rate of 15~20 ml/min with Krebs solution saturated with 95% O2 and 5% CO2, and maintained at 36+/-1 degrees C. Substantia gelatinosa neurons were identified by their location. Under a binocular microscope and with transmitted illumination, the substantia gelatinosa was clearly discernible as a relatively translucent band across the dorsal horn. The resistance of patch clamp electrodes was 8~12 Msigma. Signals were gained by using an Axopatch 200B amplifier with low-passfiltered at 5 kHz, and digitized at 333 kHz with an A/D converter. The results are as follows. (1) To see whether or not ET has any effects on the local miniature excitatory postsynaptic currents (mEPSC), the holding potential was set up at -70 mV. Under such a condition extracellular superfusion was made with 1 micromol/L TTX for 2 min first, which was followed by consistent application of 500 micromol/L ET and 1 micromol/L TTX for 1 min. It was shown that ET did not influence the decay time, frequency and amplitude of mEPSC, when compared to the control. (2) To see whether or not ET has any effects on the local miniature inhibitory postsynaptic currents (mIPSC) mediated by GABA(A) receptor, the holding potential was set up at 0 mV. Under this condition extracellular superfusion was made with 1 micromol/L TTX and 1 micromol/L strychnine, an antagonist of glycine receptor, for 2 min, and then with consistent application of 50 micromol/L ET, 1 micromol/L TTX and 1 micromol/L strychnine for 1 min. ET prolonged the decay time of GABAergic mIPSC by 45.57+/-12.46% (P<0.05), but did not influence the frequency and amplitude of GABAergic mIPSC, when compared with the control. (3) To see whether or not ET has any effects on the local mIPSC mediated by glycine receptor, the holding potential was also set up at 0 mV, and under this condition extracellular superfusion was made with 1 mmol/L TTX and 10 mmol/L bicuculline, an antagonist also set up at 0 mV, and under this condition extracellular superfusion was made with 1 micromol/L TTX and 10 micromol/L bicuculline, an antagonist of GABA(A) receptor, for 2 min, and then with consistent application of 50 micromol/L ET, 1 micromol/L TTX and 10 micromol/L bicuculline for 1 min. ET had no effects on decay time, frequency and amplitude of glycinergic mIPSC. The above-mentioned results show that ET plays anesthetic or analgesic roles by modulating the decay time of GABAergic mIPSC, i.e. by prolonging the mean open time of GABA(A) receptors, however, ET has no direct effect on local excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
Anesthetics, Intravenous
;
pharmacology
;
Animals
;
Etomidate
;
pharmacology
;
Male
;
Neurons
;
physiology
;
Patch-Clamp Techniques
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, GABA
;
metabolism
;
Spinal Cord
;
physiology
;
Substantia Gelatinosa
;
physiology
;
Synaptic Transmission
;
drug effects
8.Effect-Site Concentration of Remifentanil for Minimizing Cardiovascular Changes by Inhalation of Desflurane.
Hee Jin JEONG ; Hee Jung BAIK ; Jong Hak KIM ; Youn Jin KIM ; Jae Hyon BAHK
Yonsei Medical Journal 2013;54(3):739-746
PURPOSE: This study aims to investigate the most appropriate effect-site concentration of remifentanil to minimize cardiovascular changes during inhalation of high concentration desflurane. MATERIALS AND METHODS: Sixty-nine American Society of Anesthesiologists physical status class I patients aged 20-65 years were randomly allocated into one of three groups. Anesthesia was induced with etomidate and rocuronium. Remifentanil was infused at effect-site concentrations of 2, 4 and 6 ng/mL in groups R2, R4 and R6, respectively. After target concentrations of remifentanil were reached, desflurane was inhaled to maintain the end-tidal concentration of 1.7 minimum alveolar concentrations for 5 minutes (over-pressure paradigm). The systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and end-tidal concentration of desflurane were measured for 5 minutes. RESULTS: The end-tidal concentration of desflurane increased similarly in all groups. The SBP, DBP, MAP and HR within group R4 were not significantly different as compared with baseline values. However, measured parameters within group R2 increased significantly 1-3 minutes after desflurane inhalation. The MAP within group R6 decreased significantly at 1, 2, 4, and 5 minutes (p<0.05). There were significant differences in SBP, DBP, MAP and HR among the three groups 1-3 minutes after inhalation (p<0.05). The incidence of side effects such as hyper- or hypo-tension, and tachy- or brady-cardia in group R4 was 4.8% compared with 21.8% in group R2 and 15.0% in group R6. CONCLUSION: The most appropriate effect-site concentration of remifentanil for blunting hemodynamic responses by inhalation of high concentration desflurane is 4 ng/mL.
Adult
;
Aged
;
Androstanols/adverse effects/pharmacology
;
Anesthetics/adverse effects/pharmacology
;
Anesthetics, Inhalation/adverse effects/*pharmacology
;
Blood Pressure/drug effects
;
Etomidate/adverse effects/pharmacology
;
Female
;
Heart/*drug effects
;
Heart Rate/drug effects
;
Humans
;
Isoflurane/adverse effects/*analogs & derivatives/pharmacology
;
Male
;
Middle Aged
;
Piperidines/adverse effects/*therapeutic use
;
Protective Agents/adverse effects/*therapeutic use
9.Effects of etomidate on descending activation of motoneurons in neonatal rat spinal cord in vitro.
Acta Physiologica Sinica 2012;64(2):155-162
Descending activation pathways in spinal cord are essential for inducing and modulating autokinesis, but whether the effects of general anesthetic agents on the descending pathways are involved in initiation of skeletal muscle relaxation or not, as well as the underlying mechanisms on excitatory amino acid receptors still remain unclear. In order to explore the mechanisms underlying etomidate's effects on descending activation of spinal cord motoneurons (MNs), the conventional intracellular recording techniques in MNs of spinal cord slices isolated from neonatal rats (7-14 days old) were performed to observe and analyze the actions of etomidate on excitatory postsynaptic potential (EPSP) elicited by electrical stimulation of the ipsilateral ventrolateral funiculus (VLF), which was named VLF-EPSP. Etomidate at 0.3, 3.0 (correspond to clinical concentration) and 30.0 µmol/L were in turn perfused to MN with steadily recorded VLF-EPSPs. At low concentration (0.3 µmol/L), etomidate increased duration, area under curve and/or half-width of VLF-EPSP and N-methyl-D-aspartate (NMDA) receptor-mediated VLF-EPSP component (all P < 0.05), as well as amplitude, area under curve and half-width of non-NMDA receptor-mediated VLF-EPSP component (all P < 0.05), or decreased amplitude and area under curve of VLF-EPSP, its NMDA receptor component, and non-NMDA receptor component (all P < 0.05). However, at 3.0 and 30.0 µmol/L, it was only observed that etomidate exerted inhibitory effects on amplitude and/or duration and/or area under curve of VLF-EPSP (P < 0.05 or P < 0.01) with concentration- and time-dependent properties. Moreover, NMDA receptor-mediated VLF-EPSP component was more sensitive to etomidate at ≥ 3.0 µmol/L than non-NMDA receptor-mediated VLF-EPSP component did. As a conclusion, etomidate, at different concentrations, exerts differential effects on VLF-EPSP and glutamate receptors mediating the synaptic transmission of descending activation of MNs in neonatal rat spinal cord in vitro.
Anesthetics, Intravenous
;
pharmacology
;
Animals
;
Animals, Newborn
;
Efferent Pathways
;
physiology
;
Electric Stimulation
;
Etomidate
;
pharmacology
;
Excitatory Postsynaptic Potentials
;
drug effects
;
physiology
;
Female
;
In Vitro Techniques
;
Male
;
Motor Neurons
;
physiology
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, N-Methyl-D-Aspartate
;
drug effects
;
physiology
;
Spinal Cord
;
physiology