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T Kushikata

Publications and source records attributed to T Kushikata.

At least 19 recordsLinked to original sources
PubMed2005

Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia.

General anesthetics modulate autonomic nervous system function including thermoregulatory control, which resides in the preoptic area of the anterior hypothalamus. However, the mechanism by which anesthetics modulate hypothalamic function remains unknown. We hypothesized that isoflurane increases norepinephrine release in the preoptic area and in the posterior hypothalamus causing hypothermia during anesthesia. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo studies: 1) Norepinephrine release was measured by microdialysis in the preoptic area or the posterior hypothalamus (n=9 each) before, during (30 min), and after (50 min) rats were anesthetized with 2% isoflurane. 2) In five rats, blood gases and arterial pressure were measured. 3) Body temperature changes (n=6 each) were measured after prazosin (0, 0.05, 0.5 microg), norepinephrine (0, 0.1, 1.0 microg), or 0.5 microg prazosin with 1.0 microg norepinephrine injection into the preoptic area. In vitro study: Norepinephrine release was measured from anterior or posterior hypothalamic slices (n=10 each) incubated with 0, 1, 2, or 4% isoflurane in Ca2+-containing buffer or with 4% isoflurane (n=10) in Ca2+-free buffer. Data were analyzed with repeated measures or factorial ANOVA and Student-Newman-Keuls tests. P<0.05 was significant. During anesthesia, norepinephrine release in the preoptic area was increased approximately 270%, whereas the release in the posterior hypothalamus remained unchanged. During emergence, posterior hypothalamic norepinephrine release increased by approximately 250% (P<0.05). Rectal temperature changes correlated with norepinephrine release from the preoptic area. Norepinephrine in the preoptic area enhanced isoflurane-induced hypothermia, while prazosin reversed it. Norepinephrine release from anterior hypothalamic slices increased at all isoflurane concentrations, but only at the highest concentration in posterior hypothalamic slices. Under Ca2+-free conditions, 4% isoflurane increased norepinephrine from both regions. These results suggest that augmentation of norepinephrine release in the preoptic area is responsible for hypothermia during general anesthesia.

Anesthesia↗
PubMed2003

Orexinergic neurons and barbiturate anesthesia.

Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As we have also recently reported that OXs selectively evoke norepinephrine release from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may result from of an interaction with central orexinergic systems. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo, the effects of i.c.v. OX A, B and SB-334867-A (OX1 receptor antagonist) on pentobarbital, thiopental or phenobarbital-induced anesthesia times (loss of righting reflex) was assessed. In vitro effects of barbiturates and SB-334867-A on OX-evoked norepinephrine release from cerebrocortical slice was examined. In Chinese hamster ovary cells expressing human OX1/OX2 receptors OX A- and B-evoked increases in intracellular Ca2+ were measured with and without barbiturates. OX A and B significantly decreased pentobarbital, thiopental and phenobarbital anesthesia times by 15-40%. SB-334867-A increased thiopental-induced anesthesia time by approximately by 40%, and reversed the decrease produced by OX A. In vitro, all anesthetic barbiturates inhibited OX-evoked norepinephrine release with clinically relevant IC50 values. A GABAA antagonist, bicuculline, did not modify the inhibitory effects of thiopental and the GABAA agonist, muscimol, did not inhibit norepinephrine release. In addition there was no interaction of barbiturates with either OX1 or OX2 receptors. Collectively our data suggest that orexinergic neurons may be an important target for barbiturates, and GABAA, OX1 and OX2 receptors may not be involved in this interaction.

Animals↗
PubMed2003

Effects of nicardipine and diltiazem on the bispectral index and 95% spectral edge frequency.

BACKGROUND AND OBJECTIVE: Previous studies have shown that L-type voltage-sensitive Ca2+ channel blocking agents increased and the L-type Ca2+ channel activator Bay K 8644 reduced the general anaesthetic potency in animals. As the bispectral index correlates with the depth of sedation, we examined whether L-type Ca2+ channel blocking agents affect the bispectral index. METHODS: Thirty hypertensive patients (systolic arterial pressure >160 mmHg) presenting for total intravenous anaesthesia with propofol, fentanyl and ketamine were recruited. Bispectral index monitoring was commenced directly the patients arrived in the operating theatre. All patients were given either nicardipine or diltiazem intravenously at the discretion of the anaesthesiologist in charge. RESULTS: Twenty-three and seven patients received nicardipine or diltiazem, respectively. The bispectral index level (mean (95% confidence interval)) did not change with either drug. In the nicardipine group, the bispectral index at 0, 5, 10 and 15 min was 55 (52-58), 55 (51-59), 55 (52-59) and 56 (53-59), respectively. In the diltiazem group, values were 59 (48-71), 60 (51-70), 61 (52-71) and 61 (50-72), respectively. Both L-type Ca2+ channel blocking agents significantly decreased arterial pressure. CONCLUSIONS: Clinical doses of nicardipine and diltiazem do not alter the bispectral index during general anaesthesia.

Adult↗
PubMed2001

Effects of nociceptinNH2 and [Nphe1]nociceptin(1-13)NH2 on rat brain noradrenaline release in vivo and in vitro.

We have investigated the effects of nociceptin/orphanin FQ (NC) receptor agonist NCNH2 and a competitive NC receptor antagonist, [Nphe1]NC(1-13)NH2 on noradrenaline (NA) release in vivo using microdialysis in freely moving animals and in vitro from cerebrocortical slices. One nmol of NCNH2 injected into rat locus coeruleus inhibited NA release from the prefrontal cortex (E(max) 27.4+/-5.7% 30 min after injection) which was partially (33%) reversed by 100 nmol of [Nphe1]NC(1-13)NH2. In cerebrocortical slices NCNH2 inhibited NA release in a concentration-dependent manner (EC50 12 nM, E(max) 29.4%) that was reversed by [Nphe1]NC(1-13)NH2. In both preparations, [Nphe1]NC(1-13)NH2 per se was inactive. These data demonstrate an inhibition of NA release by NCNH2 in a [Nphe1]NC(1-13)NH2 sensitive manner in both in vivo brain microdialysis and in vitro cerebrocortical slices studies in rats.

Animals↗
PubMed2001

Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia.

PURPOSE: To study the effects of sevoflurane and isoflurane on noradrenaline release from the rat preoptic area (POA). METHOD: Sixteen male Wistar rats were studied. A microdialysis probe with a 2 mm long semipermeable membrane was implanted in the POA. Dialysates were collected at intervals often minutes. After obtaining five control samples for 50 min, 30 min inhalation of 3% sevoflurane or 1.8% isoflurane was performed. After cessation of the inhalation, five more samples were obtained for 50 min as recovery phase. Noradrenaline (NA) concentration in the dialysates was measured by high pressure liquid chromatography with an electrochemical detector. RESULTS: Both sevoflurane and isoflurane caused marked increases in NA release from the rat POA (sevoflurane 233% at 20 min, isoflurane 357% at ten minutes after the start of inhalation). The marked NA releases were also observed during the emergence from sevoflurane and isoflurane anesthesia (sevoflurane 269% at 20 min, isoflurane 368% at ten minutes in the recovery phase). CONCLUSION: This study suggests that enhanced release of NA in the POA during sevoflurane and isoflurane may explain the excitatory phase observed during the peri-anesthetic period with these agents.

Anesthesia↗
PubMed2001

Orexin A and B evoke noradrenaline release from rat cerebrocortical slices.

1. Orexin A and B, recently identified in the rat hypothalamus are endogenous neuropeptide agonists for the G-protein coupled orexin-1 (OX1) and orexin-2 (OX2) receptors. 2. In the present study, we have examined the effects of orexin A, B and raised extracellular K(+) on noradrenaline release from the rat cerebrocortical slice. We have compared this with other sleep-wake-related (excitatory) neurotransmitters; dopamine, glutamate, serotonin and histamine. 3. Neurotransmitter release studies were performed in rat cerebrocortical slices incubated in modified Krebs buffer (with and without Ca(2+)+EGTA 1 mM) with various concentrations of orexin A, B and K(+) for various times. 4. Orexin A and B-evoked (10(-7) M) noradrenaline release was time-dependent reaching a maximum some 10 min after stimulation. K(+) (40 mM) evoked release was also time dependent but reached a maximum after 6 min. Orexin A, B and K(+) stimulation of release was concentration dependent with pEC(50) and E(max) (% of basal) values of 8.74+/-0.32 (1.8 nM) and 263+/-14% and 8.61+/-0.38 (2.4 nM) and 173+/-7% and 1.43+/-0.02 (37 mM) and 1430+/-70%, respectively. Orexin-evoked release was partially extracellular Ca(2+) dependent. 5. Of the other transmitters studied there was a weak orexin A and B stimulation of glutamate release. In contrast K(+) evoked dopamine, glutamate, histamine and serotonin release with pEC(50) and E(max) (% of basal) values of 1.47+/-0.05 (34 mM) and 3430+/-410%, 1.38+/-0.04 (42 mM) and 1240+/-50%, 1.47+/-0.02 (34 mM) and 480+/-10% and 1.40+/-0.05 (40 mM) and 560+/-60% respectively. 6. We conclude that the neuropeptides orexin A and B evoke noradrenaline release from rat cerebrocortical slices.

Animals↗
PubMed2001

Effects of isoflurane and ketamine on sleep in rabbits.

The postoperative sleep disturbance (POSD) is characterized by reduction of sleep after surgical operation. However, its mechanism is not well known. Therefore, we hypothesized that anesthetics could contribute to the POSD, and studied the effects of isoflurane and ketamine on sleep in rabbits. Rabbit sleep was measured for 21 h after isoflurane exposure or intravenous injection of ketamine. Non-rapid eye movement sleep (NREMS) was decreased after isoflurane anesthesia. In contrast, ketamine anesthesia significantly enhanced NREMS. Both anesthetics did not affect rapid eye movement sleep. These results suggest that isoflurane may contribute to the POSD, but ketamine may decrease the POSD.

Anesthetics, Dissociative↗
PubMed2001

Recovery of intraoperative microbicidal and inflammatory functions of alveolar immune cells after a tobacco smoke-free period.

BACKGROUND: Tobacco smoking inhibits alveolar macrophage function, but cessation of smoking markedly reduces the risk of postoperative pulmonary complications. The authors therefore evaluated the effect of nonsmoking duration on both antimicrobial and inflammatory functions of alveolar macrophages during anesthesia and surgery. METHODS: The authors studied 15 patients who had never smoked, 15 current smokers, and 41 former smokers, all of whom underwent general anesthesia. Former smokers were further allocated to one of three groups depending on their smoke-free periods: 2 months (n = 13), 3-5 months (n = 13), and 6-12 months (n = 15). Alveolar immune cells were collected by bronchoalveolar lavage immediately after induction of anesthesia, at 2 and 4 h after induction of anesthesia, and at the end of surgery. Opsonized and nonopsonized phagocytosis were measured. Microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly. Finally, we determined the expression of proinflammatory cytokines, including interleukin 1beta, interleukin 8, interferon gamma, and tumor necrosis factor alpha, and of antiinflammatory cytokines (interleukin 4 and 10) by semiquantitative polymerase chain reaction. RESULTS: Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages (antimicrobial functions) decreased 20-50%, and the expression of genes for all proinflammatory and antiinflammatory cytokines increased 3-30-fold over time in all groups. Starting 4 h after induction of anesthesia, the decreases in antimicrobial functions were 1.5-3 times greater in current and former smokers (2 months' abstinence) than in patients who had never smoked. Starting 4 h after anesthesia, the increase in expression of all cytokines, except interleukin 8, was twofold to fivefold less in current and former smokers (2-6 months' abstinence) than in patients who had never smoked. CONCLUSION: Our data suggest that former smokers may have a limited ability to mount effective pulmonary immune defenses for long as 6 months after stopping cigarette use.

Adult↗
PubMed2001

Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells.

OBJECTIVE: Anesthesia and surgery decrease antimicrobial and increase proinflammatory functions of alveolar immune cells. Thus, anti-inflammatory agents that do not further suppress antimicrobial functions are required. We tested the hypothesis that intraoperative prostaglandin E1 (PGE1) suppresses proinflammatory responses and prevents the reduction in antimicrobial responses of alveolar immune cells. DESIGN: Prospective, randomized, controlled, double-blind study. SETTING: University hospital. PATIENTS: A total of 40 patients undergoing elective orthopedic surgery under propofol/fentanyl anesthesia. INTERVENTION: In double-blind fashion, the patients received PGE1 from the beginning to the end of surgery (PGE1 group, n = 20) or nothing (control group, n = 20). METHODS AND MAIN RESULTS: Alveolar immune cells were harvested by bronchoalveolar lavage immediately after induction of anesthesia; 2, 4, and 6 hrs after induction of anesthesia; and at the end of surgery. We measured opsonized and nonopsonized phagocytosis. Microbicidal activity was evaluated to directly kill Listeria monocytogenes in alveolar macrophages. Finally, we determined the expression of proinflammatory cytokines including interleukin (IL)-1beta, IL-8, interferon-gamma, and tumor necrosis factor-alpha, and that of anti-inflammatory cytokines (IL-4 and IL-10) by semiquantitative polymerase chain reaction. Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages decreased and the expression of genes for all pro- and anti-inflammatory cytokines increased significantly over time in both groups. Starting 2-4 hrs after induction of anesthesia, the increases in gene expression of proinflammatory cytokines were 1.5-3 times smaller in the PGE1 than in the control group. Starting 6 hrs after anesthesia, the increase in gene expression of IL-10 was 1.5-3 times greater in the PGE1 than in the control group. Intraoperative decreases in phagocytic and microbial activities were the same in the two groups. CONCLUSION: Intraoperative PGE1 not only suppressed proinflammatory responses, but also protected antimicrobial functions of alveolar macrophages, possibly because PGE1 is mostly inactivated in the pulmonary intravascular space. Our results suggest that intraoperative PGE1 protects the pulmonary immune defense in alveolar immune cells.

Adult↗
PubMed2001

Glial cell line-derived neurotrophic factor promotes sleep in rats and rabbits.

Various growth factors (e.g., growth hormone-releasing hormone, acidic fibroblast growth factor, nerve growth factor, brain-derived neurotrophic factor, and interleukin-1) are implicated in sleep regulation. It is hypothesized that neuronal activity enhances the production of such growth factors, and they in turn form part of the sleep regulatory mechanism. Glial cell line-derived neurotrophic factor (GDNF) promotes development, differentiation, maintenance, and regeneration of neurons, and its production is induced by well-characterized sleep regulatory substances such as interleukin-1 and tumor necrosis factor. Therefore, we investigated whether GDNF would promote sleep. Twenty-six male Sprague-Dawley rats and 30 male New Zealand White rabbits were surgically implanted with electroencephalogram (EEG) and electromyogram (EMG; rats only) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and on a separate day with one of the following doses of GDNF: 5, 50, and 500 ng in rabbits and 50 and 500 ng in rats. The EEG, brain temperature, EMG (in rats), and motor activity (in rabbits) were recorded for 23 h after the intracerebroventricular injection. GDNF (500-ng dose) increased the time spent in nonrapid eye movement sleep in both rats and rabbits. Rapid eye movement sleep was not affected by the lower doses of GDNF but was inhibited in rabbits after the high dose. EEG slow-wave activity was not affected by GDNF. The current results provide further evidence that various growth factors are involved in sleep regulation.

Animals↗
PubMed2001

[A case of long-term respiratory management following resection of a huge facial hemangioma].

A 49 year-old-woman was scheduled for resection of a huge hemangioma of the face and neck region. After the resection, severe edema developed on the tongue, larynx, and pharynx even leaving no space between the tracheal tube and these tissues. Prolonged respiratory management with endotracheal tube intubation was needed to maintain the upper airway for more than three weeks. Tracheostomy was performed 27 days after the operation. Two weeks later, the edema of the upper airway subsided. Thereafter her clinical course was uneventful, and she was discharged 22 days after the tracheostomy. Resection of a huge facial and neck hemangioma should be carefully managed as it can be followed by unexpected severe postoperative upper airway edema leading to suffocation.

Edema↗
PubMed2000

Intrathecal methylprednisolone for intractable postherpetic neuralgia.

BACKGROUND: There is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder. METHODS: We enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period. RESULTS: There was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons). CONCLUSIONS: The results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.

Aged↗
PubMed2000

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.

Anesthetics↗
PubMed2000

Nuclear factor-kappaB inhibitor peptide inhibits spontaneous and interleukin-1beta-induced sleep.

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-kappaB activation would attenuate sleep. A NF-kappaB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 microg for rats, 100 microg for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-microg dose of IP in rats and the 100-microg dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 microg of the IP 12 h before intracerebroventricular injection of IL-1beta (10 ng) significantly attenuated IL-1beta-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-kappaB is a crucial factor in physiological sleep regulation.

Animals↗