Kumiko Oi

Inhalation sedation with sevoflurane: A comparative study with nitrous oxide

PURPOSE To evaluate the possibility of using sevoflurane for inhalation sedation. PATIENTS AND METHODS Thirty-five volunteers were divided randomly into two groups: sevoflurane group (n = 20) and nitrous oxide (N2O) group (n = 15). At the beginning of the sedation they all inhaled 100% O2, then a 0.1 minimum alveolar concentration (MAC) of sevoflurane or 10% N2O with oxygen, a 0.2 MAC of sevoflurane or 20% N2O with oxygen, and 0.3 MAC of sevoflurane or 30% N2O with oxygen for 10 minutes each. RESULTS The respiratory and cardiovascular functions were stable during inhalation of the gas mixtures. There were five negative comments about breathing N2O, but none about breathing sevoflurane. CONCLUSION All subjects in the sevoflurane group stated they would be willing to submit to the same inhalation procedure again.

Mouth-opening Increases Upper-airway Collapsibility without Changing Resistance during Midazolam Sedation

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to −3.6 ± 2.9 cm H2O compared with −8.7 ± 2.8 (p = 0.002) for closed mouths and −7.2 ± 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 ± 6.6 vs. 17.7 ± 7.6 vs. 21.5 ± 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 ± 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

Two-dimensional jaw tracking and EMG recording system implanted in the freely moving rabbit

A system for simultaneously recording mandibular position in the sagittal plane together with masticatory muscle activity was designed and tested in rabbits. Two small magnetic sensors were implanted in the maxillary bone and a powerful magnet made of a rare earth metal attached to the mandibular central incisors. The magnetic sensors detected the mandibular movements in the sagittal plane by movement of the magnet. Masseter EMG was recorded by fine wire electrodes and amplified by a specially designed amplifier. The necessary preamplifiers were assembled as an integrated circuit (IC) chip in a small housing. The signals from the preamplifier were then passed through a signal processing unit and taped on an instrumentation tape. The system was applied to the freely moving rabbit supplied with food and water during the night. It worked without any trouble for more than 24 h. Since the implanted magnetic sensors were stable for more than 4 months, long-term recording could be done by merely reimplanting the magnet, the cables and the EMG electrodes, which was simple.

Conflict situation increases serotonin release in rat dorsal hippocampus : in vivo study with microdialysis and Vogel test

The release of serotonin (5-hydroxytryptamine, 5-HT) in the dorsal hippocampus was measured using an in vivo microdialysis method in rats subjected to the Vogel type conflict test. The conflict situation significantly increased 5-HT release in the dorsal hippocampus. Midazolam (0.75 and 1.5 mg/kg i.p.) suppressed the dosage-dependently this increased 5-HT release, an inhibition closely associated with the attenuation of conflict behavior. These findings suggest that the activation of serotonergic neuronal activity in the dorsal hippocampus is linked to mediation of anxiety-related behavior.

The compensatory responses to upper airway obstruction in normal subjects under propofol anesthesia

Upper airway obstruction during sleep can trigger compensatory neuromuscular responses and/or prolong inspiration in order to maintain adequate minute ventilation. The aim of this study was to investigate the strength of these compensatory responses during upper airway obstruction during propofol anesthesia. We assessed respiratory timing and upper airway responses to decreases in nasal pressure in nine propofol anesthetized normal subjects under condition of decreased (passive) and increased (active) neuromuscular activity. Critical closing pressure (PCRIT) and upstream resistance (RUS) were derived from pressure-flow relationships generated from each condition. The inspiratory duty cycle (IDC), maximum inspiratory flow (V1max) and respiratory rate (f) were determined at two levels of mean inspiratory airflow (VI; mild airflow limitation with VI > or = 150 ml s-1; severe airflow limitation with VI < 150 ml s-1). Compared to the passive condition, PCRIT decreased significantly (5.3 +/- 3.8 cm H2O, p < 0.05) and RUS increased (7.4 cm H2O ml-1 s, p < 0.05) in the active condition. The IDC increased progressively and comparably as decreased in both the passive and active conditions (p < 0.05). These findings imply that distinct compensatory mechanisms govern the modulation of respiratory pattern and pharyngeal patency during periods of airway obstruction under propofol anesthesia.

Effect of Mandibular Position on Upper Airway Collapsibility and Resistance

It has been proposed that advancement of the mandible is a useful method for decreasing upper airway collapsibility. We carried out this study to test the hypothesis that mandibular advancement induces changes in upper airway patency during midazolam sedation. To explore its effect, we examined upper airway pressure-flow relationships in each of 4 conditions of mouth position in normal, healthy subjects (n = 9). In the neutral position, Pcrit (i.e., critical closing pressure, an index of upper airway collapsibility) was −4.2 cm H2O, and upstream resistance (Rua) was 21.2 cm H2O/L/sec. In the centric occlusal position, Pcrit was −7.1 cm H2O, and Rua was 16.6 cm H2O/L/sec. In the incisor position, Pcrit was significantly reduced to −10.7 cm H2O, and Rua was significantly reduced to 14.0 cm H2O/L/sec. Mandibular advancement significantly decreased Pcrit to −13.3 cm H2O, but did not significantly influence Rua (22.1 cm H2O/L/sec). We conclude that the mandibular incisors’ position improved airway patency and decreased resistance during midazolam sedation.

The Effect of Gender on Compensatory Neuromuscular Response to Upper Airway Obstruction in Normal Subjects Under Midazolam General Anesthesia

BACKGROUND: Upper airway patency may be compromised during sleep and anesthesia by either anatomical alterations (mechanical properties) or disturbances in the neural control (compensatory neuromuscular responses). The pathophysiology of upper airway obstruction during anesthesia may differ between men and women. Recently, we reported that the upper airway mechanical properties were comparable with those found during natural nonrapid eye movement sleep, as evaluated by measurements of passive critical closing pressure (PCRIT) and upstream resistance (RUS) during midazolam sedation. In this study, we compared the effects of gender on compensatory neuromuscular responses to upper airway obstruction during midazolam general anesthesia. METHOD: Thirty-two subjects (14 men and 18 women) were studied. We constructed pressure-flow relationships to evaluate PCRIT and RUS during midazolam anesthesia. The midazolam anesthesia was induced with an initial dose of midazolam (0.07–0.08 mg/kg bolus) and maintained by midazolam infusion (0.3–0.4 &mgr;g · kg−1 · min−1), and the level of anesthesia was assessed by Ramsay score (Level 5) and Observer’s Assessment of Alertness/Sedation score (Level 2). Polysomnographic and hemodynamic variables were monitored while nasal pressure (via mask), inspiratory air flow (via pneumotachograph), and genioglossal electromyograph (EMGGG) were recorded. PCRIT was obtained in both the passive condition, under conditions of decreased EMGGG (passive PCRIT), and in an active condition, whereas EMGGG was increased (active PCRIT). The difference between the active PCRIT and passive PCRIT (&Dgr;PCRIT P − A) was calculated in each subject to determine the compensatory neuromuscular response. RESULTS: The difference between the active PCRIT and passive PCRIT (&Dgr;PCRIT A − P) was significantly greater in women than in men (4.6 ± 2.8 cm H2O and 2.2 ± 1.7 cm H2O, respectively; P < 0.01), suggesting greater compensatory neuromuscular response to upper airway obstruction independent of arousal. CONCLUSION: We demonstrate that the arousal-independent compensatory neuromuscular responses to upper airway obstruction during midazolam anesthesia were partially maintained in women, and that gender may be a major determinant of the strength of compensatory responses during anesthesia.

Variation of the jaw-opening reflex during spontaneous mastication in rabbits

To understand the modulation of periodontal mechanoreceptor activity on mastication, the jaw-opening reflex (JOR) evoked by electrical stimulation of the inferior alveolar nerve (IAN) was studied during chewing in freely behaving rabbits. Spontaneous chewing movements were intact from the IAN stimulation below two times the threshold (T) which was measured at rest. As the stimulus intensity was increased to more than 2.5 T, the amplitude of the masseter activity decreased or it was abolished; however, the chewing rhythm was still maintained up to 3.0 T. When the low-threshold primary afferents were tested while the rabbit chewed pellets rhythmically, the amplitude in the JOR was inhibited below the prior control level. The inhibitory effect on the JOR was larger in the opening phase than that in the closing phase. In conclusion, the JOR was tonically depressed during the masticatory cycle and the inhibition of the JOR was rhythmically modulated in a phase-linked manner that was larger in the opening phase than in the closing phase.

Interaction between the N-terminal and Middle Regions Is Essential for the in Vivo Function of HSP90 Molecular Chaperone

At the primary structure level, the 90-kDa heat shock protein (HSP90) is composed of three regions: the N-terminal (Met1–Arg400), middle (Glu401–Lys615), and C-terminal (Asp621–Asp732) regions. In the present study, we investigated potential subregion structures of these three regions and their roles. Limited proteolysis revealed that the N-terminal region could be split into two fragments carrying residues Met1 to Lys281 (or Lys283) and Glu282 (or Tyr284) to Arg400. The former is known to carry the ATP-binding domain. The fragments carrying the N-terminal two-thirds (Glu401–Lys546) and C-terminal one-third of the middle region were sufficient for the interactions with the N- and C-terminal regions, respectively. Yeast HSC82 that carried point mutations in the middle region causing deficient binding to the N-terminal region could not support the growth of HSP82-depleted cells at an elevated temperature. Taken together, our data show that the N-terminal and middle regions of the HSP90 family protein are structurally divided into two respective subregions. Moreover, the interaction between the N-terminal and middle regions is essential for the in vivo function of HSP90 in yeast.

Propofol produces anticonflict action by inhibiting 5-HT release in rat dorsal hippocampus.

WE examined the effect of propofol, an injectable anesthetic agent on conflict behavior in a Vogel type conflict test and on release of serotonin (5-hydroxytryptamine, 5-HT) in the dorsal hippocampus using an in vivo microdialysis method in rats. Propofol (20 and 40 mg/kg, i.p.) dose-dependently suppressed elevated 5-HT release normally seen in a conflict situation and concomitantly attenuated conflict behavior. These findings suggest that propofol exerts an antianxiety action by inhibiting 5-HT neuronal activity in the dorsal hippocampus.