Kazuhiko Watanabe

The determinants of propofol induction of anesthesia dose

Recently it was reported that the pharmacokinetics of propofol are modified by changes in cardiac output. The objective of this study was to evaluate the effects of cardiac output and other factors on the hypnotic dose of propofol. One-hundred surgical patients were administered indocyanine green immediately before the induction of anesthesia to measure their cardiac outputs and blood volumes. Propofol (250 &mgr;g · kg−1 · min−1) was infused IV for 8 min, and the hypnotic dose of propofol and the time to hypnosis were recorded. The plasma concentration of propofol immediately after 2 mg/kg infusion was measured. Multiple regression analysis showed that, in addition to age and weight, cardiac output was a small but significant factor for predicting the hypnotic dose of propofol (R2 = 0.468, P < 0.001), the time to hypnosis (R2 = 0.454, P < 0.001), and the plasma concentration of propofol (R2 = 0.248, P < 0.01). Cardiac output, age, and weight showed similar partial coefficients for the hypnotic dose (0.128, 0.137, and 0.140, respectively).

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.

Fentanyl attenuates the hemodynamic response to endotracheal intubation more than the response to laryngoscopy.

We examined the effectiveness of avoiding laryngoscopy in reducing the hemodynamic responses to orotracheal intubation during the induction of anesthesia. One hundred surgical patients who required orotracheal intubation were randomly allocated into four groups. The first and third groups underwent fiberoptic intubation, in which an anesthesiologist inserted the endotracheal tube into the trachea under TV monitoring through a bronchoscope, and the second and fourth groups underwent conventional orotracheal intubation using a rigid laryngoscope. The third and fourth groups were pretreated with 2 &mgr;g/kg fentanyl IV immediately before the induction of anesthesia. Blood pressure and heart rate were measured noninvasively. A significant reduction in hemodynamic response was seen in only the group treated with fentanyl and intubated using the fiberoptic technique. Without fentanyl, there was no significant difference in hemodynamic changes between the groups. We conclude that the administration of fentanyl suppresses the hemodynamic responses to endotracheal intubation more than it does to laryngoscopy. There was no significant difference in the hemodynamic responses to orotracheal intubation by fiberscopy and laryngoscopy without fentanyl pretreatment, whereas 2 &mgr;g/kg fentanyl significantly reduced the hemodynamic responses in the group intubated by fiberscopy.

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.

Oxygen inhalation enhances striatal dopamine metabolism and monoamineoxidase enzyme inhibition prevents it: a microdialysis study

In order to explore the effect of normobaric oxygen on the extracellular level of dopamine and its metabolites, oxygen (30, 60 and 90%) was administered to freely moving rats after the animals had been pretreated with either monoamineoxidase (MAO)-A and -B inhibitors (0.1 or 1 mg kg(-1) of clorgyline, 1 or 10 mg kg(-1) of selegiline and 75 mg kg(-1) pargyline) or control solution. The levels of dopamine and its metabolites were monitored in microdialysis samples collected every 20 min and directly applied to an on-line high-performance liquid chromatograph combined with electrochemical detection. Normobaric oxygen inhalation decreased the level of extracellular dopamine and increased that of 3,4-dihydroxyphenylacetic acid (DOPAC) in a concentration-dependent manner. These changes were partly prevented by pre-treatment with low doses of selegiline or clorgyline, i.e. by conditions in which monoamineoxidase-A or -B was inhibited. When both isoforms of monoamineoxidase were inhibited, there was a drastic increase in extracellular concentrations of dopamine and 3-methoxytyramine, and the levels of DOPAC and homovanilic acid (HVA) were very low. These results indicate that the intracellular metabolism of cytoplasmic dopamine is enhanced by normobaric hyperoxia in rat striatum.

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.

Isoflurane anesthesia inhibits clozapine- and risperidone-induced dopamine release and anesthesia-induced changes in dopamine metabolism was modified by fluoxetine in the rat striatum: An in vivo microdialysis study

Previously, we have reported that halothane anesthesia increases the extracellular concentrations of dopamine (DA) metabolites in the rat striatum using in vivo microdialysis techniques, and we have suggested that volatile anesthetics affect DA release and metabolism in various ways. The present investigation assesses the effect of isoflurane, widely used in clinical anesthesia, on DA release and metabolism. A microdialysis probe was implanted in the striatum of male Sprague-Dawley rats (n=5-7 per group). After recovery, the probe was perfused with modified Ringers solution and 40 microl of dialysate were injected into a high performance liquid chromatograph every 20 min. The rats were given saline or the same volume of 10 mg kg(-1) clozapine, risperidone, fluoxetine or citalopram. After the pharmacological treatment, the rats were anesthetized with 1.0% or 2.5% isoflurane for 1h. The data were analyzed using two-way analysis of variance (ANOVA). For each drug with significant (p<0.05) drug-time interactions, the statistical analysis included one-way ANOVA and Newman-Keuls post hoc comparisons. A high concentration of isoflurane (2.5%) anesthesia increased the extracellular concentration of DA metabolites during emergence from anesthesia. The levels of DA metabolites increased in an isoflurane concentration-dependent manner. Isoflurane attenuated DA release induced by clozapine and risperidone. Fluoxetine, but not citalopram, antagonized the isoflurane-induced increase in metabolites. The results of current investigation suggest that isoflurane enhances presynaptic DA metabolism, and that the oxidation of DA might be partially modulated by the activities of the dopaminergic-serotonergic pathway at a presynaptic site in the rat striatum.

Rapid fluid infusion therapy decreases the plasma concentration of continuously infused propofol.

Background:  Rapid fluid infusion therapy to treat hypovolemia in anesthetized patients is a common practical regimen in daily clinical settings. This study investigated the effect of large volume loading on the plasma concentration of propofol (Cp), hemodynamic parameters, hemoglobin concentration (Hb), hematocrit value (Ht) and the bispectral index (BIS).

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.

Pentobarbital inhibits L-DOPA-induced dopamine increases in the rat striatum: An in vivo microdialysis study.

Pentobarbital is reported to inhibit ketamine-induced dopamine (DA) release in the rat nucleus accumbens. The accumbens is a part of the limbic dopaminergic system in the brain, and the dopaminergic neural activity of other components may also be sensitive to pentobarbital. We investigated the effect of pentobarbital administration on DA release in the striatum known as DA-rich basal ganglia, and the interaction between pentobarbital and L-DOPA, using in vivo microdialysis techniques. Male SD rats were implanted microdialysis probe into the right striatum. The probe was perfused with modified Ringers solution and dialysate was directly injected to an HPLC. Every group of rats was consisted of six to seven animals. In the first experiment, rats were given saline, 25 and 50 mg kg(-1) pentobarbital. The second, each rat was given a local administration of 2 and 5 microg ml(-1) of L-DOPA with perfusate. Finally, other sets of rats were given 5 microg ml(-1) of L-DOPA and 25, 50, or 100 mg kg(-1) pentobarbital. Pentobarbital anaesthesia decreased the extracellular concentration of DA, and local administration of L-DOPA significantly increased DA concentration. Pretreatment with pentobarbital diminished the L-DOPA-induced DA increase. The results of the present investigation demonstrate that administration of pentobarbital might inhibit dopaminergic neural activity not only in the nucleus accumbens but also in the rat striatum. Pentobarbital anaesthesia antagonizes DA increase induced by L-DOPA and suggests the inhibition of metabolism of L-DOPA. The results of some animal experiments on dopaminergic activity under pentobarbital anaesthesia should be reconsidered.