Koki Hirota

The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro

UNLABELLED It is unclear whether general anesthetics induce enhancement of neural inhibition and/or attenuation of neural excitation. We studied the effects of pentobarbital (5 x 10(-4) mol/L), propofol (5 x 10(-4) mol/L), ketamine (10(-3) mol/L), halothane (1.5 vol%), and isoflurane (2.0 vol%) on both excitatory and inhibitory synaptic transmission in rat hippocampal slices. Excitatory or inhibitory synaptic pathways were isolated using pharmacological antagonists. Extracellular microelectrodes were used to record electrically evoked CA1 neural population spikes (PSs). In the presence of the gamma-aminobutyric acid type A (GABA(A)) receptor antagonist (bicuculline), the inhibitory actions of pentobarbital and propofol were completely antagonized, whereas those of ketamine, halothane, and isoflurane were only partially blocked. To induce the N-methyl-D-aspartate (NMDA) receptor-mediated PS (NMDA PS), the non-NMDA and GABA(A) receptors were blocked in the absence of Mg2+. Ketamine, halothane, and isoflurane decreased the NMDA PS, and pentobarbital and propofol had no effect on the NMDA PS. The non-NMDA receptor-mediated PS (non-NMDA PS) was examined using the antagonists for the NMDA and GABA(A) receptors. Volatile, but not i.v., anesthetics reduced the non-NMDA PS. These findings indicate that pentobarbital and propofol produce inhibitory actions due to enhancement in the GABA(A) receptor; that ketamine reduces NMDA receptor-mediated responses and enhances GABA(A) receptor-mediated responses; and that halothane and isoflurane modulate GABA(A), NMDA, and non-NMDA receptor-mediated synaptic transmission. IMPLICATIONS Volatile anesthetics modulate both excitatory and inhibitory synaptic transmission of in vitro rat hippocampal pathways, whereas i.v. anesthetics produce more specific actions on inhibitory synaptic events. These results provide further support the idea that general anesthetics produce drug-specific and distinctive effects on different pathways in the central nervous system.

The Pentax‐AWS® rigid indirect video laryngoscope: clinical assessment of performance in 320 cases*

The Pentax‐AWS® airway scope system is a rigid indirect video laryngoscope with integrated tube guidance. Laryngoscopy and intubation are visualised using a built in LCD monitor which displays the view obtained by a CCD camera mounted in the tip of the laryngoscope. We describe its clinical performance in 320 patients. The Pentax‐AWS significantly improved the laryngeal view compared to the Macintosh laryngoscope. Forty‐six patients (14%) who were classified as Cormack Lehane glottic view grade 3 or 4 using the Macintosh laryngoscope were classified as grade 1 (45 cases) or 2a (1 case) using the Pentax‐AWS airway scope. Laryngeal views measured by percentage of glottic opening score were improved significantly using the Pentax‐AWS. Intubation using the Pentax‐AWS was successful in all cases, 96% at the first and 4% at the second attempt. The mean (SD) time required to place the tracheal tube was 20 (10) s. The Cormack Lehane grade obtained with the Macintosh blade did not affect the total time to correctly position the tube using the Pentax‐AWS. Intubation difficulty scale (score = 0 in 305 patients, score = 1 in 14 and score = 2 in one patient) indicates that tracheal intubation was performed easily in most cases. The Pentax‐AWS not only improves the laryngeal view, but its tube guide also facilitates rapid, easy and reliable tracheal intubation under vision. It can be useful in routine anesthesia care and may be advantageous in the situation of unanticipated difficult intubation.

GABAergic mechanisms in the action of general anesthetics.

1. The effects of volatile and intravenous anesthetics were studied on evoked field potentials in rat hippocampal CA1 neurons in vitro to determine the role of GABAergic mechanisms in the action of general anesthetics. 2. It was observed that both volatile (halothane, isoflurane, sevoflurane) and intravenous (thiopental, pentobarbital, propofol) anesthetics decreased population spike (PS) amplitudes. 3. Using paired-pulse paradigms, it was revealed that volatile agents enhance paired-pulse facilitation (PPF), and intravenous agents reduce PPF. Use-dependent effects on PS amplitudes were observed following application of the intravenous anesthetics, whereas volatile agents did not show use-dependency. The effects of the intravenous anesthetics were blocked by the GABA(A) receptor antagonist, bicuculline. 4. It is suggested that agent specific actions of general anesthetics are a result of differential effects on GABAergic mechanisms that modulate synaptic transmission.

Intravenous anesthetics are more effective than volatile anesthetics on inhibitory pathways in rat hippocampal CA1.

In this study, we have examined the effects of both volatile and IV general anesthetics on excitatory synaptic transmission, with and without recurrent inhibition, to clarify whether excitatory or inhibitory synapses are the major targets of action. Field population spike amplitudes (fPSs) of CA1 pyramidal neurons were recorded in rat hippocampal slices. Schaffer-collateral-commissural fibers (Sch) were stimulated orthodromically, and the evoked fPSs (PS[Sch]) in CA1 area were measured. In addition, the fPSs (PS[Alv+Sch]) elicited by stimulation of the Sch after antidromic stimulation of the alveus hippocampi (Alv) to produce recurrent inhibition were determined. It was observed that sevoflurane (0.5%–5%) and isoflurane (0.5%–5%) primarily inhibited PS[Sch] and also produced additive inhibition on the PS[Alv+Sch] in a concentration-dependent manner. The calculated 50% effective concentration (EC50) values for PS[Sch] and PS[Alv+Sch] were 5.3 vol% and 3.9 vol% (sevoflurane) and 1.7 vol% and 1.1 vol% (isoflurane), respectively. In comparison, thiopental (2.0 × 10−5–5.0 × 10−4 mol/L) reduced both the PS[Sch] and PS[Alv+Sch] in a concentration-dependent manner. The calculated EC50 values for thiopental on PS[Sch] and PS[Alv+Sch] were 3.4 × 10−4 and 5.7 × 10−5 mol/L, respectively. Propofol (2.0 × 10−5–3.5 × 10−4 mol/L) had little effect on the PS[Sch] but reduced PS[Alv+Sch] with a calculated EC50 value of 5.1 × 10−4 mol/L. The effects of the IV anesthetics with recurrent inhibition were antagonized in the presence of the γ-aminobutyric acid-A-receptor antagonist bicuculline methiodide. In addition, all anesthetics prolonged recurrent inhibition from 100 ms (sevoflurane and isoflurane) to 400 ms (propofol). The results suggest that sevoflurane and isoflurane inhibit mainly on glutamate-mediated orthodromic pathways, whereas thiopental and propofol enhance γ-aminobutyric acid-A-mediated recurrent inhibitory pathways in CA1 neurons, thus providing further evidence that the mechanisms of general anesthetics are drug- and pathway-specific.

Extracellular Magnesium Ion Modifies the Actions of Volatile Anesthetics in Area CA1 of Rat Hippocampus In Vitro

Background Magnesium ion (Mg2+) is involved in important processes as modulation of ion channels, receptors, neurotransmitter release, and cell excitability in the central nervous system. Although extracellular Mg2+ concentration ([Mg2+]o) can be altered during general anesthesia, there has been no evidence for [Mg2+]o-dependent modification of anesthetic actions on neural excitability in central nervous system preparations. The purpose of current study was to determine whether the effects of volatile anesthetics are [Mg2+]o-dependent in mammalian central nervous system. Methods Extracellular electrophysiologic recordings from CA1 neurons in rat hippocampal slices were used to investigate the effects of [Mg2+]o and anesthetics on population spike amplitude and excitatory postsynaptic potential slope. Results The depression of population spike amplitudes and excitatory postsynaptic potential slopes by volatile anesthetics were significantly dependent on [Mg2+]o. The effects were attenuated in the presence of a constant [Mg2+]o/extracellular Ca2+ concentration ratio. However, neither N-methyl-d-aspartate receptor antagonists nor a non–N-methyl-d-aspartate receptor antagonist altered the [Mg2+]o-dependent anesthetic-induced depression of population spikes. Volatile anesthetics produced minimal effects on input–output (excitatory postsynaptic potential–population spike) relations or the threshold for population spike generation. The effects were not modified by changes in [Mg2+]o. In addition, the population spike amplitudes, elicited via antidromic (nonsynaptic) stimulation, were not influenced by [Mg2+]o in the presence of volatile anesthetics. Conclusions These results provide support that alteration of [Mg2+]o modifies the actions of volatile anesthetics on synaptic transmission and that the effects could be, at least in part, a result of presynaptic Ca2+ channel–related mechanisms.

Uric acid excretion increases during propofol anesthesia

We compared the effect of propofol with that of sevoflurane anesthesia on uric acid (UA) excretion in ASA physical status I and II patients with normal renal function.A propofol group (n = 11) received propofolnitrous oxide-fentanyl after induction of anesthesia by propofol, while a sevoflurane group (n = 12) received sevoflurane-nitrous oxide-fentanyl after induction of anesthesia by thiamylal. UA, creatinine (Cr), and urea nitrogen concentrations in serum and urine were measured before induction of anesthesia, 1, 2, and 3 h after induction, and on Postoperative Day 1. N-acetyl-beta-D-glucosaminidase, beta2-microglobulin concentrations, and pH in urine were also examined. Plasma clearance of UA (CUA) and Cr (CCr) were calculated. The hourly concentration and excretion of urine UA were significantly higher than those of the sevoflurane group (P < 0.01). Significant correlations were noted between the hourly urine volume and UA concentration (r = 0.58, P < 0.01 for the propofol group; r = 0.51, P < 0.01 for the sevoflurane group). The CUA of the propofol group was significantly higher than that of the sevoflurane group (22.9 +/- 10.6 vs 5.9 +/- 3.4 mL/min, mean +/- SD, P < 0.05). There were no significant differences in other renal variables between the two groups. The present study demonstrated that the UA excretion increased during propofol anesthesia, while it remained stable during sevoflurane anesthesia. (Anesth Analg 1997;85:144-8)

Misuse of infusion pump during propofol anaesthesia

To the Editor: We read with interest the recent case report by Tong et al. describing recall after total intravenous anaesthesia due to equipment misuse, l They experienced two misuses; one is uncommon (the latch was not clamped to the plunger) and the other is common (the system bad no t been purged to confirm the delivery visually). We would like to suggest that one possible cause of intraoperative awareness is the flow interrupt ion of propofol which occurs when the syringe is exchanged wi thout purging. An infusion pump (STC-525X; Terumo) was used. A 50 ml syringe (Terumo) containing 50 ml propofol or saline and fitted with a 21-gauge needle was loaded into the pump wi thout purging. Twelve combinations of body weight (40, 60, 80 kg) and infusion rate (4, 6, 8, 10 mg.kg-Lhr q ) were evaluated. After the infusion pump was turned on, the delay until the second droplet o f the solution was observed from the needle was measured five times. This delay increased in the lower infusion dose, and closely matched power curves in both solutions (see Table below). Saline had a longer delay than did propofol. The main reason for the delay is probably sticking of the pluuger, as a longer delay was observed for the lower infusion dose. 2 Small gaps in the grooves in which the syringe ear and plunger end are loaded may also contribute to the delay. Although the delay may vary for different infusion pumps and syringe brands, the syringe should be purged to prevent intraoperative awareness.

Presynaptic actions of general anesthetics are responsible for frequency-dependent modification of synaptic transmission in the rat hippocampal CA1.

BACKGROUND: In clinical anesthesia, robust surgical stress occasionally causes unintended light anesthesia during operation. To test the hypothesis that neural input condition could modify actions of general anesthetics as a result of presynaptic alteration in the central nervous system, we investigated the mechanisms by which the stimulus frequency modifies synaptic transmission of the rat hippocampus in the presence of general anesthetics. METHODS: Field population spikes (PSs) of CA1 pyramidal neurons were elicited using orthodromic stimulation of Schaffer collateral-commissural fibers (test-pulse). A second stimulating electrode was placed in the region of the alveus hippocampi to activate recurrent inhibition of area CA1 (pre-pulse). The pre-pulses were applied as train stimuli (100–200 Hz) to activate release and then deplete the neurotransmitter (&ggr;-aminobutyric acid [GABA]) at presynaptic terminals of inhibitory interneurons. RESULTS: After the activation of inhibitory interneurons with pre-pulses, both IV (thiopental and pentobarbital) and volatile (sevoflurane and isoflurane) anesthetics attenuated the PS amplitudes elicited with test-pulses (test-PS). The IV anesthetics, but not the volatile drugs, produced stimulus frequency- and use-dependent recurrent inhibition of test-PSs. Neither a GABA type A agonist nor a GABA uptake inhibitor produced frequency-dependent modification. The pre-pulse train protocol revealed that IV anesthetics, but not volatile drugs, can enhance GABA release from presynaptic terminals. CONCLUSIONS: IV anesthetics, but not volatile drugs, enhance the discharge of a readily releasable pool of GABA vesicles from presynaptic terminals. Depletion of an active pool of GABA after high-frequency stimuli would produce frequency- and use-dependent recurrent inhibition in the presence of IV anesthetics. The stimulus frequency-dependent modification of synaptic transmission might be responsible for the unsuccessful immobilization or hypnosis during general anesthesia after IV anesthetic administration.

Perioperative anesthetic managements for the laryngo‐tracheal separation and open fundoplication in a 17‐year‐old patient with Leigh syndrome

the patient was difficult to ventilate because of the presence of blood in the airway. Necessarily, high airway pressures were used to maintain adequate tidal volumes and this almost undoubtedly exacerbated the entry of air in the pulmonary vasculature. This is the first case report of a pediatric patient where a bronchovenous fistula developing during RFA; however, air embolism and massive hemorrhage have been individually reported in association with RFA (3,5,6). Systemic air embolism has been reported a number of times during transthoracic needle biopsy (4,7) and cases of presumed bronchovenous fistula have also been reported during needle biopsy of lung lesions (4,8). One author also suggested that needle passage through areas of abnormal tissue may increase the risk of this complication (4). Although this event was nearly fatal, the patient responded to conservative management without longterm sequelae. Practitioners need to be aware that such serious complications can occur during RFA and may be more likely when lung compliance is reduced and positive pressure ventilation is occurring.

Pre-synaptic function explains age-dependent actions of general anesthetics in the rat hippocampal synaptic transmission

Mechanisms by which age modifies general anesthetic requirements remain uncertain. In order to examine the age-related modification of general anesthetics in the central nervous system, we have studied the effects of thiopental and sevoflurane on hippocampal synaptic transmission in young and elderly rats. Field potentials of area CA1 were electrically elicited in hippocampal slices from young (4-month) and elderly (2-year) male Wistat rats. The effects of sevoflurane on both excitatory and inhibitory synaptic transmission were similar in the young and elderly preparations. In contrast, thiopental produced a greater effect on inhibitory synaptic transmission in young than elderly hippocampi, whereas the actions on excitatory synaptic transmission were negligible in both preparations. Corresponding experiments revealed (a) that the duration of recurrent inhibition was more prolonged by thiopental in young compared to elderly animals and (b) that thiopental enhanced the γ-amino-butyric acid (GABA) release from pre-synaptic terminals in an age-dependent manner. The thiopental actions on GABA discharge from pre-synaptic terminals appear to be responsible for the observed difference between young and elderly animals. The age-dependent reduction in neurotransmitter stores in pre-synaptic terminals may explain the age-related alterations in general anesthetic actions.