Yushi Adachi

Isoflurane anesthesia induces biphasic effect on dopamine release in the rat striatum.

The effect of isoflurane anesthesia on changes in the extracellular concentrations of dopamine (DA) and its metabolites (3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) modulated by pargyline, monoamine oxidase inhibitor, was studied using in vivo microdialysis techniques. A microdialysis probe was implanted into the right striatum of male SD rats. Each rat (n=5-6) was given saline or the same volume of 30 or 75 mg kg(-1) pargyline intraperitoneally with or without 1 h isoflurane anesthesia (1 or 3%). Isoflurane anesthesia increased the extracellular concentration of DA in high dose (3%) and increased the metabolite concentrations in a dose-dependent manner. Pargyline administration increased the extracellular concentration of DA and 3-MT, and decreased that of other metabolites. After 30 mg kg(-1) pargyline treatment, 1% isoflurane-induced DA release and increasing of 3-MT were preserved, whereas high dose isoflurane (3%) decreased the concentration of metabolites (DOPAC and HVA), despite of the increase by low dose isoflurane (DOPAC). When 75 mg kg(-1) pargyline was administered, isoflurane anesthesia decreased the concentration of DA and DOPAC. The isoflurane-induced 3-MT increase was preserved in all experiments. Our results suggest that isoflurane anesthesia induced biphasic effect on DA regulation probably by the potentiation of DA release and the inhibition of DA synthesis. Isoflurane might modulate DA homeostasis presynaptically.

Effect of dexmedetomidine on the release of [3H]-noradrenaline from rat kidney cortex slices: characterization of α2-adrenoceptor

The presynaptic modulation of [3H]-noradrenaline (NA) release from rat kidney cortex slices, a method used for the first time, was investigated. Rat kidney cortex slices were loaded with [3H]-NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha(2)-adrenoceptor agonist, dexmedetomidine inhibited the stimulation-evoked release of NA from kidney slices in a concentration-dependent manner, whereas alpha(2)-adrenoceptor antagonist CH-38083 (7,8-methyenedioxy-14-alpha-hydroxyalloberbane HCl), an alpha(2)-adrenoceptor antagonists, enhanced it. When dexmedetomidine and BRL-44408, a selective alpha(2A) antagonist, were added together, the effect of dexmedetomidine was significantly antagonized. In contrast, ARC-239 (2-(2,4-(o-piperazine-1-yl)-ethyl-4,4-dimethyl-1,3-(2H, 4H)disoguinolinedione chloride), a selective alpha(2B)-antagonist, had no effect on the release and failed to prevent the effect of dexmedetomidine. Prazosin, an alpha(1)- and alpha(2B/C)-adrenoceptor antagonist enhanced the release evoked by field stimulation. It is therefore suggested that there is a negative feedback modulation of NA release at the sympathetic innervation of kidney cortex, and dexmedetomidine, a clinically used anesthetic adjunct inhibits the release via activation of alpha(2C)-adrenoceptors.

Compound A Concentrations During Low-Flow Sevoflurane Anesthesia Correlate Directly with the Concentration of Monovalent Bases in Carbon Dioxide Absorbents

UNLABELLED: Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Potassium hydroxide (KOH) and sodium hydroxide (NaOH) are primary determinants of this degradation reaction. To address this, new carbon dioxide absorbents, such as Amsorb((R)) (A; Armstrong Medical, Coleraine, Northern Ireland), which contains neither KOH nor NaOH, Dragersorb 800 Plus((R)) (D; Drager, Luebeck, Germany), and Medisorb((R)) (M; Datex-Ohmeda, Bromma, Sweden), which contain some NaOH (1% to 2%) and only trace amounts of KOH (0.003%), were recently developed. We compared Compound A concentrations using these three CO(2) absorbents during low-flow (1 L/min) sevoflurane anesthesia in surgical patients, with those using a conventional CO(2) absorbent, Dragersorb 800 (C). The mean Compound A concentrations +/- SD using C, A, D, and M were 18.7 +/- 2.5, 1.8 +/- 0.7, 13.3 +/- 3.5, and 11.2 +/- 2.6 ppm, respectively, with significant differences (P < 0.001; A versus C, A versus D, A versus M, C versus D, C versus M). Amsorb prevented the degradation of sevoflurane to Compound A, whereas Dragersorb 800 Plus and Medisorb decreased the degradation to Compound A. IMPLICATIONS: Sevoflurane degradation to Compound A is decreased by lowering the concentration of monovalent bases in the carbon dioxide absorbent (Dragersorb 800 Plus) [Drager, Luebeck, Germany] and Medisorb) [Datex-Ohmeda, Bromma, Sweden]) and is virtually eliminated in the absence of these bases (Amsorb) [Armstrong Medical, Coleraine, Northern Ireland]).

The influence of lumbosacral cerebrospinal fluid volume on extent and duration of hyperbaric bupivacaine spinal anesthesia: a comparison between seated and lateral decubitus injection positions.

We designed the present study to examine the influence of lumbosacral cerebrospinal fluid (CSF) volume on the spread and duration of hyperbaric bupivacaine spinal anesthesia when the injection is made with the patient in the lateral position compared with that when the patient is in a seated position. Seventy-four patients undergoing peripheral orthopedic or urogenital surgery with spinal block were enrolled. Lumbosacral CSF volumes were calculated from axial magnetic resonance images. Patients were randomly assigned to 1 of 2 groups: the lateral (L) and seated (S) groups (n = 37 each). Spinal anesthesia (3 mL hyperbaric 0.5% bupivacaine) was administered using a 25-gauge pencil-type needle with the needle aperture directed cephalad and the patient in the lateral decubitus position with the non-operated side up (L group) or with the patient in a seated position (S group). Patients were turned supine immediately after spinal injection (L group) or after remaining seated for 2 min (S group). Statistical correlation coefficients (&rgr;) were assessed using Spearman’s rank correlation. There were negative correlations between CSF volume and peak sensory block level in both the L (&rgr; = −0.69, P < 0.0001) and S groups (&rgr; = −0.68, P < 0.0001). In the S group, but not in the L group, CSF volume significantly correlated with onset time of peak sensory block level (&rgr; = −0.48, P = 0.004), and time required for regression to L1–4 (P < 0.05–0.01). We conclude that CSF volume influences the spread of spinal anesthesia with hyperbaric bupivacaine regardless of patient position when the spinal injection is made. CSF volume influenced the duration of spinal sensory anesthesia when the injection was made with the patient in a seated position, but not in the lateral position.

Halothane anesthesia decreases the extracellular level of dopamine in rat striatum: a microdialysis study in vivo

AbstractPurpose. In our previous microdialysis study, sevoflurane or isoflurane anesthesia significantly decreased the extracellular level of dopamine in rat striatum in vivo. On the other hand, other investigators demonstrated that halothane anesthesia either increased or did not affect the extracellular dopamine level. To explore the differences among these volatile anesthetics, the effects of halothane and nitrous oxide on the striatal dopamine level were reinvestigated. Methods. Halothane alone, nitrous oxide with or without halothane, or drugs known to affect the dopaminergic pathway were administered to rats. Microdialysates were collected every 20 min and directly applied to an on-line high-performance liquid chromatograph without any pretreatment. The effects of halothane on respiratory and cardiovascular variables were monitored. Results. General anesthesia with halothane alone de-creased the dialysate (extracellular) concentration of dopamine but increased that of dopamine metabolites. Nitrous oxide alone slightly increased dopamine metabolites in dialysates but did not affect the halothane-induced decrease in extracellular dopamine. Apomorphine and haloperidol reproduced reported results, confirming the adequacy of our methodology. Nomifensine- or methamphetamine-induced increase in extracellular dopamine was augmented by halothane. Conclusion. These results suggest that halothane po-tently enhances striatal dopamine release and activates the reuptake or metabolic process, which is consistent with our previous results for sevoflurane or isoflurane. Volatile anesthetics interfere with dopamine regulation, at least in the rat striatum.

The Carbon Dioxide Absorption Capacity of Amsorb® is Half That of Soda Lime

A new CO2 absorbent, Amsorb® (A), which does not contain monovalent bases, is ideal because it does not degrade volatile anesthetics to either Compound A (from sevoflurane) or carbon monoxide (from desflurane, enflurane, or isoflurane). The CO2 absorption capacity of A, however, has not been investigated under clinical conditions. In this study, we compared the longevity (time to exhaustion) and CO2 absorption capacity (the volume of CO2 absorbed before CO2 rebreathing occurs) of A under low-flow anesthesia (1 L/min) with those of two soda lime absorbents—Medisorb® (M) and Sodasorb® (S)—by using a 750-mL ADU canister and a 1350-mL Aestiva 3000 canister. In the study with the ADU canister, the longevity of A was 213 ± 71 min, significantly less than those of M (445 ± 125;P < 0.01) and S (503 ± 89;P < 0.001). The CO2 absorption capacity (L/100 g absorbent) of A was 5.5 ± 1.2, significantly less than those of M (10.7 ± 1.7) and S (12.1 ± 1.8;P < 0.001). In the study with the Aestiva 3000 canister, the longevity of A was 218 ± 61 min, significantly less than those of M (538 ± 136) and S (528 ± 103;P < 0.001). The CO2 absorption capacity (L/100 g absorbent) of A was 7.6 ± 1.6, significantly less than those of M (14.4 ± 1.8) and S (14.8 ± 2.3;P < 0.001). These results indicate that the CO2 absorption capacity of A is half that of M or S and that the difference in the CO2 absorption capacity between A and M or S is almost constant, regardless of the canister design.

Evaluation of the cardiovascular responses to fiberoptic orotracheal intubation with television monitoring: comparison with conventional direct laryngoscopy

STUDY OBJECTIVE To evaluate and compare cardiovascular responses to a new method of orotracheal intubation incorporating TV monitoring, with conventional orotracheal intubation via rigid blade laryngoscopy. DESIGN Prospective single-blind study. SETTING Operating room of a medical college hospital. PATIENTS 90 ASA physical status I and II surgical patients requiring general anesthesia and orotracheal intubation. INTERVENTIONS Patients were randomly allocated to two groups, one for the new intubation method and the other for conventional intubation using a rigid laryngoscope. In the new method, an anesthesiologist inserted an endotracheal tube alone into the trachea via TV monitoring through the bronchoscope, which was inserted by an assistant through the mouth to the middle larynx. The patients trachea was intubated without extreme stretching of laryngeal tissues or deep insertion of the tip of the bronchoscope. In the conventional method, orotracheal intubation was performed with rigid direct laryngoscopy. MEASUREMENTS Noninvasive blood pressure (BP) and heart rate (HR) were measured before arrival at the operating room, and before and after orotracheal intubation. MAIN RESULTS Although this method was expected to be a minimally invasive fiberoptic intubation technique, the patients showed significant increases in BP and HR. No significant differences between the two groups were observed in cardiovascular responses immediately after intubation: the systolic BP, 169.5 +/- 28.3 versus 167.0 +/- 23.1 mmHg, and HR, 100.2 +/- 18.2 versus 98.8 +/- 16.6 bpm. CONCLUSIONS Insertion of an endotracheal tube may itself be the most invasive stimulus during intubation procedures.

Halothane attenuated haloperidol and enhanced clozapine-induced dopamine release in the rat striatum

The effect of halothane anesthesia on changes in the extracellular concentrations of dopamine (DA) and its metabolites (3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA)) induced by neuroleptics was studied using in vivo microdialysis techniques. Halothane attenuated haloperidol-induced dopamine release and enhanced clozapine-induced dopamine release in the rat striatum.A microdialysis probe was implanted into the right striatum of male SD rats. Rats were given saline or the same volume of 200 microg kg(-1) haloperidol (D(2) receptor antagonist), 10 mg kg(-1) sulpiride (D(2) and D(3) antagonist), or 10 mg kg(-1) clozapine (D(4) and 5-HT(2) antagonist) intraperitoneally with or without 1-h halothane anesthesia (0.5 or 1.5%). Halothane anesthesia did not change the extracellular concentration of DA, but increased the metabolite concentrations in a dose-dependent manner. The increased DA concentration induced by haloperidol was significantly attenuated by halothane anesthesia, whereas the metabolite concentrations were unaffected. Halothane had no effect on the changes in the concentrations of DA or its metabolites induced by sulpiride. The clozapine-induced increases in DA and its metabolites were enhanced by halothane anesthesia. Our results suggest that halothane anesthesia modifies the DA release modulated by antipsychotic drugs in different ways, depending on the effects of dopaminergic or serotonergic pathways.

Halothane enhances acetylcholine release by decreasing dopaminergic activity in rat striatal slices.

The present study investigated the effect of halothane on acetylcholine (ACh) and dopamine (DA) release from the rat striatum. Halothane decreased DA release in a concentration-dependent manner, while increased ACh release. In our previous investigation, a volatile anesthetic, halothane, inhibited DA release from the rat striatal slices in a concentration-dependent manner. Although the release of ACh from cholinergic interneurons is tonically modulated by DA in the striatum, the effect of halothane on the relationship between the release of ACh and DA has not been discussed. Using double-labeled techniques, we investigated the effect of halothane on ACh and DA release simultaneously. The slices were incubated with [14C]-choline and [3H]-DA and superfused with modified Krebs solution containing 1 microM of hemicholinium-3. We applied electrical field stimulation (2 Hz, 240 shocks), and the amount of the release of radioactivity evoked by stimulation was calculated by subtraction of the basal radioactive outflow from the total outflow at the beginning of the respective stimulation periods. The effects of drugs on the release were expressed as the ratio of stimulation-evoked fractional releases (FR), measured in the presence and absence (FRS2/FRS1) of the drug. Halothane decreased DA release in a concentration-dependent manner (FRS2/FRS1=0.767+/-0.021, 0.715+/-0.026, 0.671+/-0.014 and 0.639+/-0.033 at the concentration of 0, 0.5, 2 and 4%, respectively), while ACh release showed a biphasic change in the presence of different concentrations of halothane. The release of ACh was significantly increased at the concentration of 2%, but not at 0.5 or 4%. Halothane failed to increase the release of ACh in striatal slices after lesion by 6-OH-dopamine. The application of amphetamine reduced the release of ACh and abolished the effect of halothane. These results indicate that the effect of halothane on ACh release is indirect: it increases the release by attenuating the inhibitory effect of DA released from the nigro-striatal pathway. The nonsynaptic interaction between DA and ACh release is involved in the effect of halothane on ACh release.

A small dose of midazolam decreases the time to achieve hypnosis without delaying emergence during short-term propofol anesthesia

STUDY OBJECTIVE To evaluate the effect of a small dose of midazolam (10 microg kg(-1)) on induction and emergence during short-term propofol anesthesia and to investigate the effects of subsequent administration of flumazenil. DESIGN Double-blinded, prospective, randomized study. SETTING Operating room of a medical college hospital. PATIENTS 30 male ASA physical status I and II patients (ages 51 to 75) scheduled for minor surgery under spinal anesthesia. INTERVENTIONS Patients were randomly allocated to one of three groups: the placebo-propofol-placebo (PP) group, the midazolam-propofol-placebo (MP) group, or the midazolam-propofol-flumazenil (MF) group. After administering placebo or midazolam (10 microg kg(-1)), propofol 250 microg kg(-1) min(-1) was infused. Immediately after confirming that the patient was hypnotized, we terminated the propofol infusion and administered placebo or flumazenil (5 microg kg(-1)). MEASUREMENTS The dose and the times required to achieve hypnosis (the first endpoint) and to emerge from anesthesia (the second endpoint). The plasma concentration at each endpoint was determined. MAIN RESULTS Midazolam significantly decreased the dose and time needed to achieve hypnosis [PP vs. MP, 66 +/- 14 vs. 48 +/- 15 mg, 260 +/- 55 vs. 179 +/- 44 sec, respectively (mean +/- SD)]. Thus, the plasma concentration of propofol at hypnosis was significantly lower (PP vs. MP, 3.31 +/- 0.78 vs. 2.41 +/- 0.57 microg mL(-1)). The time to emerge from anesthesia was not prolonged by midazolam, and was further shortened by administration of flumazenil (PP, MP vs. MF, 237 +/- 77, 207 +/- 71 s vs. 126 +/- 56 sec, respectively). Flumazenil also reversed the reduction in propofol concentration induced by midazolam at emergence (PP, MP, and MF, 0.54 +/- 0.17, 0.37 +/- 0.15, and 0.59 +/- 0.22 microg mL(-1), respectively). CONCLUSIONS Coadministration of 10 microg kg(-1)midazolam decreases the dose and time required to achieve hypnosis with propofol induction without delaying emergence from anesthesia. Additional administration of flumazenil further shortens the time to emerge from midazolam-propofol anesthesia.