Yoshitaka Uchihashi

The disruptive effects of ketamine on passive avoidance learning in mice : involvement of dopaminergic mechanism

The involvement of dopaminergic mechanisms in ketamine-induced disruption of one trial step-through passive avoidance performance was assessed through the coadministration with the dopamine D1 antagonist SCH 23390, the dopamine D2 antagonist YM-091512 and the dopamine autoreceptor agonist at low doses, apomorphine, in mice. Pretraining (10 min before) administration of ketamine (0; saline, 2.5, 5 and 10 mg/kg SC) dose-dependently reduced the latency in the retention trial conducted 24 h after the training. However, ketamine did not affect the retention latency when administered immediately after the training or prior to retention. YM-09151-2 (0.01 and 0.03 mg/kg SC) and apomorphine (0.01 and 0.03 mg/kg SC), but not SCH 23390 (0.01 and 0.03 mg/kg SC), ameliorated the impaired reduction by ketamine (10 mg/kg) in a dose-dependent manner. These results suggest that ketamine obstructs the acquisition of the passive avoidance task, and that this effect is induced by stimulation of dopamine D2 receptors through dopamine release from the presynaptic terminals.

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.

The effect on intracuff pressure of various nitrous oxide concentrations used for inflating an endotracheal tube cuff.

UNLABELLED We sought to determine the optimal concentration of nitrous oxide (N(2)O) for inflating endotracheal tube cuffs, to avoid overinflation and air leaks. Female patients undergoing endotracheal intubation (inner diameter 7.5 mm) during anesthesia with 67% N(2)O were randomly assigned to five groups of 25 subjects each, in which cuffs were inflated with 0% (Air), 30% (N30), 40% (N40), 50% (N50), or 67% (N67) N(2)O. The cuff pressure and the N(2)O concentration in the cuff were measured. In an additional 15 patients (N40-a group), pilot balloons were replaced with metal tubes, and the mouths and noses of the patients were wrapped with tape, to minimize N(2)O efflux into the air. Postoperative sore throats were evaluated in double-blinded interviews. Cuff pressures increased significantly in the Air and N30 groups but decreased in the N67 group. Cuff pressures were <22 mm Hg in the N40 and N50 groups, but the N50 group had air leaks. The N(2)O concentration in the cuff in the N40 group was significantly smaller than that in the N40-a group, suggesting N(2)O rediffusion. The incidence of sore throats (40% in the Air group) was reduced significantly in the N40 and N50 groups. Therefore, 40% N(2)O is optimal for filling the cuff during anesthesia with 67% N(2)O. IMPLICATIONS Nitrous oxide (N(2)O) diffuses into the cuff, equilibrating at a smaller concentration than the gas mixture with which patients are ventilated. Our data indicate that inflation of the cuff with 40% N(2)O is recommended to prevent both excessive endotracheal cuff pressure and air leaks during anesthesia with 67% N(2)O, reducing postoperative sore throats.

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.

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.

Repeated ketamine administration produces up-regulation of muscarinic acetylcholine receptors in the forebrain, and reduces behavioral sensitivity to scopolamine in mice.

To study the effects of repeated ketamine administration on central muscarinic acetylcholine receptors (mAchRs), ddY male mice were administered subcutaneous doses of 25 mg/kg ketamine every 3 days for a total of five times. Receptor binding assays of mAchR were carried out in the forebrain (FB), cerebellum (CB) and brainstem (BS), using [3H]quinuclidinyl benzilate ([3H]QNB) as a ligand. In addition, we examined whether repeated ketamine (12.5, 25 and 50 mg/kg) or saline (five times) could modify the hyperlocomotion induced by scopolamine (0.5 mg/kg, SC) (a muscarinic antagonist), using a behavior-pharmacological technique. Repeating the ketamine administration resulted in a significant increase in the receptor density value (Bmax) for [3H]QNB only in FB, dependent on the numbers of administrations (1270 ± 33 fmol/mg protein for a single dose, 1620 ± 59 for four treatments, 1738 ± 70 for five treatments without any change in apparent affinity (defined as the reciprocal of the dissociation constant) (Kd). A competitive inhibition study of repeated (5 times) administration of ketamine failed to detect any subtype-specific changes in mAchRs. Repeated ketamine administration reduced the scopolamine-induced hyperlocomotion in a doserelated way, and the changes were significant at 50 mg/kg. Our results suggest that repeated ketamine administration produces an up-regulation of mAchRs, and this change may be associated with altered Ach transmission in the central nervous system.

Effects of alpha adrenoreceptor antagonists, prazosin and. yohimbine, on intrathecal lidocaine-induced antinociception in mice.

Background: The precise mechanisms involved in the spinal analgesic effect of lidocaine are not yet clear. We previously found that lidocaine releases noradrenaline, a modulator of nociception, in rat spinal cord. Here, we attempted to clarify whether or not the noradrenaline release contributes to spinal analgesia by lidocaine.

Long-term Clomipramine Treatment Upregulates Forebrain Acetylcholine Muscarinic Receptors, and Reduces Behavioural Sensitivity to Scopolamine in Mice

We have investigated the effects of long‐term treatment with clomipramine, a tricyclic antidepressant, on central muscarinic acetylcholine receptors (mAChR) in mice.

Assessment of the lingual tonsil and vallecula during fiberoptic intubation.

1 Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan 2 Medical Clinic of Kumagaya Base, Japan Air Self Defense Force, 839 Jurokuken, Kumagaya, Saitama 360-0846, Japan 3 Medical Corps of 1st Air Wing, Japan Air Self Defense Force, Nishiyama-cho, Hamamatsu, Shizuoka 432-8551, Japan 4 Department of Anesthesia, Japan Self Defense Force Hanshin Hospital, 4-1-50 Kushiro, Kawanishi, Hyogo 666-0024, Japan

Accidental subdural catheterization suspected on administration of a test dose of lidocaine and successfully managed by a small dose of dibucaine.

triple-end-hole, nylon epidural catheter was passed through the needle without difficulty and the needle eased backwards over the catheter leaving 4cm in the space. After confirming a negative response to an aspiration test, 3ml of 1% lidocaine was administered as a test dose. Immediately after this injection, the patient complained of a warm feeling around her right femur on inquiry by the anesthetist. Turning her to the supine position, we examined the level of analgesia. Five minutes after the injection, the cold sensation elicited by a small brush wetted with ethanol disappeared bilaterally at dermatomes from S3 to Th10. A pinprick test showed the same level of analgesia in the dermatomes. An aspiration test was performed repeatedly, but nothing was aspired. No motor blockade was observed at that time. Blood pressure and heart rate showed no marked change after the test dose. Thus, as scheduled, general anesthesia was induced with propofol and vecuronium, and her trachea was intubated. General anesthesia was maintained with 0.6% sevoflurane and 66% nitrous oxide. Since inadvertent subarachnoid catheterization was strongly suspected, we tried to block the nerve by applying a small dose, 2 ml, of 0.3% dibucaine. When an incision was made on her abdominal skin, no change in heart rate or blood pressure occurred (being approximately 80 beats·min21 and 120/65 mmHg, respectively), confirming satisfactory analgesia with administration of 2ml of 0.3% dibucaine. Since heart rate and blood pressure began to increase slowly 1h later up to 95 beats·min21 and 130/80 mmHg, respectively, 2ml of 0.3% dibucaine was administered through the catheter. After the operation, a radiographic examination was performed to confirm the catheter position. A watersoluble contrast medium (Isobist, Schering, Berlin Germany, 170mgI·ml21) was injected through the catheter with the patient being in the supine position. Initially, 2ml of the contrast medium was gently injected and its entry into the subdural space was observed (Fig. 1). The