歯科口腔外科手術における高齢患者の麻酔方法と術前合併疾患に関する検討

歯科口腔外科手術における高齢患者の麻酔方法と術前合併疾患に関する検討


Pronounced QTc Prolongation During General Anesthesia in a Child with Left Ventricular Non-Compaction Cardiomyopathy


機器紹介 インターサージカル個人防護用呼吸マスク「i-Proマスク」

機器紹介 インターサージカル個人防護用呼吸マスク「i-Proマスク」


複数回の再手術を要し血友病Bと判明した舌裂傷の1症例

複数回の再手術を要し血友病Bと判明した舌裂傷の1症例


下咽頭梨状窩瘻に対しトリクロル酢酸で化学的焼灼術を施行した1症例

下咽頭梨状窩瘻に対しトリクロル酢酸で化学的焼灼術を施行した1症例


全身麻酔導入および覚醒時に顕著なQTc延長を認めた左室心筋緻密化障害患児の1例

全身麻酔導入および覚醒時に顕著なQTc延長を認めた左室心筋緻密化障害患児の1例

Journal of Japanese Dental Society of Anesthesiology


Pronounced QTc Prolongation during Induction of and Awakening from General Anesthesia in a Child with Left Ventricular Non-compaction Cardiomyopathy : A Case Report

全身麻酔導入および覚醒時に顕著なQTc延長を認めた左室心筋緻密化障害患児の1例


細胞骨格およびIL-17制御を介した血管内皮機能維持機構の解明と麻酔薬作用

細胞骨格およびIL-17制御を介した血管内皮機能維持機構の解明と麻酔薬作用


Acute and long-term effects of haloperidol on surgery-induced neuroinflammation and cognitive deficits in aged rats.

Neuroinflammation may contribute to the pathogenesis of the cognitive symptoms of postoperative delirium (POD) and its subsequent long-term cognitive impairment. Haloperidol (HAL), a dopamine receptor antagonist, is widely used to treat POD, whereas the effects of HAL on postoperative neuroinflammation and related cognitive deficits have been underdetermined. Aged rats underwent sham or abdominal surgery and were subcutaneously treated with either vehicle, low-dose (0.5 mg/kg bolus, then 0.5 mg/kg/day infusion), or high-dose (2.0 mg/kg bolus, then 2.0 mg/kg/day infusion) HAL. All treatments were initiated immediately after surgery and continued for 48 h. On either postoperative day 2 (early) or 7 (late), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Following the cognitive testing, the levels of pro-inflammatory cytokines, as well as dopamine and its metabolite, in hippocampus and medial prefrontal cortex (mPFC) were measured. In the early postoperative period, surgery induced acute neuroinflammation along with related trace and context memory dysfunction. Dopamine turnover was increased in both hippocampus and mPFC, whereas no relationship with memory functions was observed. However, HAL even at high-dose failed to restore the surgery-induced neuroinflammation and related cognitive deficits. In the late postoperative period, chronic neuroinflammation was detected only in hippocampus, which was associated with context, but not trace memory dysfunction. Neither low- nor high-dose HAL could prevent the development of these late-phase neurocognitive deficits. Our findings indicate that perioperative administration with HAL may have no effects on postoperative neuroinflammation and related cognitive impairment.


Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats.

The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6 h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.


Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats.

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels.


Intraoperative Change in QTc in a Patient with a Prolonged QTc Interval

QTc延長患者における全身麻酔中のQTc変動

 Long QT syndrome is characterized by a prolongation of the QT interval and a morphological change in the T wave on an electrocardiogram. Prolongation of the QT interval is associated with serious arrhythmia and may cause syncope and sudden death. A 13-year-old male with a prolonged corrected QT interval (QTc) on a preoperative electrocardiogram was scheduled to undergo the extractation of a supernumerary tooth under general anesthesia.

 Although he had no remarkable past medical history, his QTc was prolonged to 514 ms on a 12-lead electrocardiogram. There was no history of syncope or sudden death in his family. The QTc at the time of his entrance into the operation room was 483 ms. During surgery, his QTc was continuously monitored in addition to the usual intraoperative monitoring. After the rapid introduction of anesthesia with remifentanil and propofol, the anesthesia was maintained with remifentanil and sevoflurane in oxygen and air. No significant change in the QTc was observed at the time of tracheal intubation accompanied by sympathetic stimulation. There was also no significant change in the QTc after the administration of atropine for bradycardia. However, when 2% lidocaine containing adrenaline was used for local anesthesia, the QTc gradually became prolonged reaching a maximum of 507 ms. In patients with a prolonged QT interval on a preoperative electrocardiogram, careful attention may be needed during the use of local anesthetics containing adrenaline. In addition, continuous monitoring of the QTc during surgery may be useful for the prevention of serious arrhythmias.


A Case of Well-Managed Fibromyalgia with Autonomic Dysfunction during Dental Therapy: Significance of Heart Rate Variability Analysis

IOSR Journal of Dental and Medical Sciences


Resveratrol-loaded nanoemulsion prevents cognitive decline after abdominal surgery in aged rats.

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway.


The role of hippocampal brain-derived neurotrophic factor in age-related differences in neuropathic pain behavior in rats.

This study was aimed to explore the contribution of central brain-derived neurotrophic factor (BDNF) in the neuropathic pain pathogenesis using an aged rodent model. Adult and aged rats were randomly assigned to either a sciatic nerve ligation (SNL) group or a control skin sham surgery group. Sensory behavioral testing were performed on the day before surgery and on the 3rd, 7th, 14th, and 21st days after surgery, followed by measurement of BDNF protein levels in different brain regions. In another experiment, the hippocampal BDNF gene expression after SNL surgery was assessed at different time-points. Furthermore, the analgesic effects of intranasal BDNF administration were tested in SNL animals. Our behavioral results demonstrated that the hyperalgesia-like behavior after painful nerve injury has a higher incidence in aged rats compared with in adult animals. In particular, the hippocampal BDNF levels were inversely correlated with the probability of hyperalgesia-type behavior, in both brain-region specific and age-dependent manner. Time-course analysis showed that the hippocampal levels of BDNF mRNA in aged and adult rats started to decrease 7 and 14 days after surgery, respectively. However, the decrease was more pronounced in aged animals. Moreover, the repeated intranasal BDNF treatment could restore the central BDNF signaling, counteracting the age-related exacerbation of hyperalgesic behavior. Our findings imply that hippocampal BDNF may be related with the pathogenesis of elderly neuropathic pain. Pharmacological data further suggest that brain BDNF may be modifiable in aged neuropathic animals, and therefore, represent a promising target for intervention.


閉塞型睡眠時無呼吸症候群を伴った成人スティル病患者の嚢胞摘出術における静脈内鎮静法下患者管理の経験


Stevens-Johnson症候群の既往がある難治性てんかん患者の全身麻酔経験


The role of hippocampal insulin signaling on postoperative cognitive dysfunction in an aged rat model of abdominal surgery.

This study aimed to investigate the role of central insulin signaling, including glycogen synthase kinase 3β (GSK-3β), and its therapeutic potential for the prevention of postoperative neurocognitive deficits. In non-insulin experiment, aged rats were divided into a sham group and abdominal surgery group. In insulin experiment, sham and surgically treated rats were distributed into two groups: an intranasal denatured insulin-treated group and intranasal insulin-treated group. Insulin administration started the day of surgery and continued for 3days. Fourteen-days after surgery, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of pro-inflammatory cytokines, GSK-3β, and phosphorylated GSK-3β (pGSK-3β(ser9)). Under identical conditions, lipopolysaccharide (LPS)-induced cytokine release from isolated hippocampal microglia was also tested. In non-insulin experiment, compared with non-surgical animals, the rats that underwent abdominal surgery showed memory deficits and increased hippocampal cytokine levels. The hippocampal ratio of pGSK-3β(ser9)/GSK-3β decreased after surgery, a ratio that was positively correlated with novel object recognition performance in the testing phase. Insulin experiment revealed that perioperative intranasal insulin administration could restore the surgery-induced hippocampal neuroinflammation and hyperactivation of GSK-3β, and prevent impairment in novel object recognition. Furthermore, ex vivo experiments indicated that intranasal insulin administration, as well as pretreatment with SB216763, a GSK-3β inhibitor, resulted in reduction of the surgery-related microglial hyper-reactivity to LPS. Our findings in aged rats suggest that surgical procedures could impair central insulin signaling including GSK-3β, which makes the individual more susceptible to hippocampal neuroinflammation and related cognitive disorders.


Pregabalin can prevent, but not treat, cognitive dysfunction following abdominal surgery in aged rats.

The present study aimed to explore the preventive or therapeutic effect of peri-operative pregabalin treatment on the memory deficits and related hippocampal inflammation following surgery in aged rats. Aged rats underwent abdominal or sham surgery, and were then divided into 2 groups, either early or late pregabalin treatment. Fourteen days after surgery, the cognitive function was assessed using novel object recognition test, followed by measurement of hippocampal cytokines and voltage-dependent calcium channel α2δ subunit (CACNA2D1). The parabiotic experiments determined whether the humoral or neuronal pathway was involved in the neuroinflammation development following the abdominal surgery. The effects of pregabalin on LPS-induced cytokine release from hippocampal microglia were also evaluated. Early pregabalin treatment, which was administered pre-operatively and continued for 3 or 7days after surgery, prevented memory deficits and decreased hippocampal pro-inflammatory cytokine levels. In contrast, no beneficial effects were observed when pregabalin was administered late in the post-operative period. The hippocampal levels of CACNA2D1 did not change under any experimental condition. The data from the cross-circulation (parabiosis) experiments indicated that abdominal surgery may induce neuroinflammation via a neural transmission pathway from the periphery to the brain. The ex vivo experiments further demonstrated that pregabalin had no effect on LPS-induced cytokines release from hippocampal microglia. Our findings highlight reveal that peri-operative pregabalin treatment during the early post-operative period can prevent neuroinflammation and memory deficits after surgery. It is likely this occurs through a peripheral and central neuro-immune interaction rather than through direct anti-inflammatory effects.


Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats

The aim of the present study was to investigate the effects and underlying mechanisms of endotoxin (lipopolysaccharide, LPS) on postoperative pain using a rat model of incisional pain. Animals were assigned to one of four groups using a 2×2 experimental design: a single intraperitoneal injection of 5mg/kg LPS versus vehicle, by plantar incision versus anesthesia alone. Spontaneous pain and mechanical paw withdrawal threshold (PWT) were evaluated using Rat Grimace Scale (RGS) and von Frey fibers, respectively. Analgesic effects of ketoprofen, morphine, and wound infiltration with ropivacaine, as well as the contribution of the Toll-like receptor (TLR) 4 pathway, were also evaluated. In vivo single fiber recordings were performed to assess the nociceptive afferent signals from the surgical site. Systemic administration of LPS significantly increased the pain intensity at 2h after hind paw incision, but did not affect the PWT. The duration of post-incisional pain assessed by both scales did not significantly differ in the presence or absence of LPS. The analgesic efficiency of ketoprofen and morphine was reduced by LPS, while that of wound infiltration with ropivacaine was preserved. On the other hand, in vivo single fiber recording failed to demonstrate any significant effects of LPS on the activity of primary afferents due to mechanical stimuli. Pre-treatment with intrathecal LPS from Rhodobacter sphaeroides, a TLR-4 antagonist, almost completely inhibited LPS-induced exacerbated post-incisional pain, and decreased analgesic responsiveness. The present results suggested that LPS exacerbates post-incisional pain via the central TLR-4 pathway.


A comparison of midazolam and dexmedetomidine for the recovery of serotonin syndrome in rats.

Serotonin syndrome is a drug-related toxicity caused by excess serotonin within the central nervous system. We recently encountered a case of serotonin syndrome that developed in the early postoperative period that was successfully treated with intravenous dexmedetomidine. Although the prescriptive literature has commonly recommended sedation with benzodiazepines for controlling agitation in serotonin syndrome, the effectiveness of dexmedetomidine has also been reported in several clinical conditions. In the present study, we conducted a reverse translational experiment to compare the efficacy of dexmedetomidine and midazolam, at equi-sedative doses, on serotonergic toxicity-like responses in rats. Animals were subcutaneously injected with 0.75 mg/kg 8-OH-DPAT, a full 5-HT1A agonist. 8-OH-DPAT-treated rats showed serotonin syndrome-like behaviors (low body posture, forepaw treading), hyperlocomotion, and decreased body temperature, which were completely inhibited by pretreatment with WAY 100635, a selective 5-HT1A antagonist (n = 8). Intramuscular injection of midazolam (1.0 mg/kg) or dexmedetomidine (0.01 mg/kg), which comparably induced observable signs of sedation, was tested in the present study. Concomitant treatment with midazolam significantly attenuated the hyperlocomotion, but failed to affect traditional serotonin syndrome behaviors and body temperature in 8-OH-DPAT-treated rats (n = 8). On the other hand, concomitant treatment with dexmedetomidine significantly attenuated all of these parameters (n = 8). The present case and related reverse translational experiment demonstrate that dexmedetomidine may be more beneficial for the treatment of serotonin syndrome compared to the current recommended treatment with benzodiazepines.


Impact of Preoperative Environmental Enrichment on Prevention of Development of Cognitive Impairment following Abdominal Surgery in a Rat Model.

Sustained neuroinflammation may contribute to the pathogenesis of postoperative cognitive dysfunction (POCD). Here, the authors evaluated the preventive effect of preoperative environmental enrichment (PEE) on the development of neuroinflammation and concomitant POCD in a rat abdominal surgery model. Young and aged rats were assigned to one of four groups using a 2 × 2 experimental design: PEE versus sedentary condition for 14 days, by abdominal surgery versus anesthesia alone (n = 8 in each group). After a 7-day postsurgical recovery period, cognitive function was assessed using a novel object recognition test, followed by measurement of hippocampal levels of proinflammatory cytokines. Under identical conditions, microglia were isolated from the hippocampus for assessment of cytokine response to lipopolysaccharide. In the sedentary group, aged, but not young, rats receiving surgery showed memory deficits (novel object preference during testing phase of 54.6 ± 7.8% vs. 76.9 ± 11.3% in nonsurgery group, P < 0.05) and increased hippocampal levels of cytokines compared with nonsurgical rats. PEE had no effects on novel object preference in nonsurgery animals (78.6 ± 10.7%), whereas it attenuated surgery-induced impairment of novel object preference (70.9 ± 15.0%, P < 0.05 vs. sedentary/surgery group) as well as increase of cytokine levels in hippocampus. Furthermore, upon ex vivo stimulation with lipopolysaccharide, cytokines release from hippocampal microglia isolated from aged rats before intervention was significantly higher in comparison with young rats. PEE resulted in reduction of these age-related microglial phenotypic changes. PEE could prevent the development of neuroinflammation and related POCD in aged rats by reversion of a proinflammatory phenotype of hippocampal microglia.


特発性間質性肺炎を合併した患者に対する口腔外科長時間手術の全身麻酔経験

特発性間質性肺炎を合併した患者に対する口腔外科長時間手術の全身麻酔経験

Journal of Japanese Dental Society of Anesthesiology


静脈穿刺により発症した血管迷走神経性失神時に心拍変動解析を行った1例

静脈穿刺により発症した血管迷走神経性失神時に心拍変動解析を行った1例


Effects of ketoprofen for prevention of postoperative cognitive dysfunction in aged rats

Postoperative cognitive dysfunction is a common geriatric complication that may be associated with increased mortality. Here, we investigated the effects of postoperative analgesia with ketoprofen on cognitive functions in aged animals and compared its effectiveness to morphine. Rats were randomly allocated to one of four groups: isoflurane anesthesia without surgery (group C), isoflurane anesthesia with laparotomy (group IL), and isoflurane anesthesia with laparotomy plus postoperative analgesia with ketoprofen or morphine. There was no difference in postoperative locomotor activity among groups. In group IL, postoperative pain levels assessed by the Rat Grimace Scale significantly increased until 8 h after surgery, which was similarly inhibited by both ketoprofen and morphine. Cognitive function was assessed using radial arm maze testing for 12 consecutive days from postoperative day 3. Results showed that the number of memory errors in group IL were significantly higher than those in goup C. However, both ketoprofen and morphine could attenuate the increase in memory errors following surgery to a similar degree. Conversely, ketoprofen showed no effect on cognitive function in the nonsurgical rats that did not experience pain. Our findings suggest that postoperative analgesia with ketoprofen can prevent the development of surgery-associated memory deficits via its pain-relieving effects.


Effects of dexmedetomidine on insulin secretion from rat pancreatic β cells

Dexmedetomidine acts as a selective α2-adrenergic receptor agonist and an imidazoline receptor agonist, both of which are known to affect insulin secretion. Here, we investigated the effects of clinically relevant concentrations of dexmedetomidine on insulin secretion under in vivo conditions. Furthermore, its underlying mechanisms were examined using isolated islets in vitro. For the in vivo oral glucose tolerance test (OGTT), male Sprague-Dawley rats were randomly allocated to one of three groups (n = 7 in each group): two groups infused with dexmedetomidine at a low (group L) or a high (group H) dose, and one control group infused with the same amount of saline (group C). For the in vitro perifusion study, insulin released from isolated islets was measured during stepwise changes in glucose. Dexmedetomidine (0.1-100 µM) was added to the chamber. During the OGTT test, the insulin levels in group H were significantly lower than those in group C at 30, 60, and 90 min after glucose load. On the other hand, insulin levels in group L were comparable to those of group C at all time points. In the perfusion study, dexmedetomidine inhibited glucose-stimulated insulin secretion in a concentration-dependent manner. When co-treated with yohimbine, an α2-adrenoceptor blocker, dexmedetomidine adversely increased glucose-induced insulin secretion. However, co-treatment with idazoxan, an antagonist for α2-adrenergic and imidazoline receptors, completely abolished the action of dexmedetomidine. Dexmedetomidine had no effect on insulin secretion at sedative dose, whereas it significantly inhibited insulin secretion at supraclinical high concentrations mainly via the α2-adrenoceptor.


Cuffed oropharyngeal airway for difficult airway management.

Abstract Difficulties with airway management are often caused by anatomic abnormalities due to previous oral surgery. We performed general anesthesia for a patient who had undergone several operations such as hemisection of the mandible and reconstructive surgery with a deltopectoralis flap, resulting in severe maxillofacial deformation. This made it impossible to ventilate with a face mask and to intubate in the normal way. An attempt at oral awake intubation using fiberoptic bronchoscopy was unsuccessful because of severe anatomical abnormality of the neck. We therefore decided to perform retrograde intubation and selected the cuffed oropharyngeal airway (COPA) for airway management. We inserted the COPA, not through the patient's mouth but through the abnormal oropharyngeal space. Retrograde nasal intubation was accomplished with controlled ventilation through the COPA, which proved to be very useful for this difficult airway management during tracheal intubation even though the method was unusual.


Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-D-aspartate receptor in aged rats.

Pain may be associated with postoperative cognitive dysfunction (POCD); however, this relationship remains under investigated. Therefore, we examined the impact of postoperative pain on cognitive functions in aged animals. Rats were allocated to the following groups: control (C), 1.2 % isoflurane for 2 hours alone (I), I with laparotomy (IL), IL with analgesia using local ropivacaine (IL+R), and IL with analgesia using systemic morphine (IL+M). Pain was assessed by rat grimace scale (RGS). Spatial memory was evaluated using a radial maze from postoperative days (POD) 3 to 14. NMDA receptor (NR) 2 subunits in hippocampus were measured by ELISA. Finally, effects of memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, on postoperative cognitive performance were tested. Postoperative RGS was increased in Group IL, but not in other groups. The number of memory errors in Group I were comparable to that in Group C, whereas errors in Group IL were increased. Importantly, in Group IL+R and IL+M, cognitive impairment was not found. The memory errors were positively correlated with the levels of NMDA receptor 2 subunits in hippocampus. Prophylactic treatment with memantine could prevent the development of memory deficits observed in Group IL without an analgesic effect. Postoperative pain contributes to the development of memory deficits after anesthesia and surgery via up-regulation of hippocampal NMDA receptors. Our findings suggest that postoperative pain management may be important for the prevention of POCD in elderly patients.


Activation of ATP-sensitive potassium channels by nicorandil is preserved in aged vascular smooth muscle cells in rats.

Nicorandil, an ATP-sensitive potassium (KATP) channel opener having the properties of a nitrate, causes vasodilation, particularly of coronary arteries, and has been reported to reduce the frequency of perioperative cardiac events. We previously demonstrated that isoflurane could activate vascular KATP channels through an intracellular signaling pathway, but that this isoflurane-induced channel opening is suppressed by aging. Here, we investigated whether advanced age modifies nicorandil-induced activation of vascular KATP channels. We used a cell-attached patch-clamp configuration to test the effects of nicorandil on KATP channel activity in vascular smooth muscle cells (VSMCs) obtained from 12- to 15-week-old (adult) and 24- to 25-month-old (aged) male Wistar rats. Bath application of nicorandil (0.1-100 μM) activated KATP channels to a level similar to that observed in VSMCs from the arteries of both adult and aged rats. Furthermore, concomitant bath application of nicorandil in the aged group dose-dependently ameliorated the age-related reduction in isoflurane-induced vascular KATP channel activation. Our findings indicate that nicorandil could be used effectively in elderly patients to directly activate vascular KATP channels during the perioperative period.


Anesthetic Management for Buccal Mucosa Tumor Resection in a Patient with Pemphigus Vulgaris

尋常性天疱瘡患者における頬粘膜腫瘍切除術の全身麻酔経験


Biophysical and Pharmacological Properties of Glucagon-Like Peptide-1 in Rats Under Isoflurane Anesthesia.

Glucagon-like peptide-1 (GLP-1) increases insulin secretion and has an important role in maintaining glucose homeostasis. In this study, we evaluated the biophysical and pharmacological properties of GLP-1 by performing in vivo and in vitro experiments to determine the applicability of GLP-1 in glycemic control in rats under isoflurane anesthesia. Levels of portal GLP-1, insulin, and glucose and dipeptidyl peptidase-4 activity were measured in the basal fasting state and after gastric glucose load before, during, and after exposure to 30% O(2) in air (control) or 1.4% isoflurane in a mixture of 30% O(2) and air. The direct effects of isoflurane on GLP-1 secretion were assessed in human enteroendocrine NCI-H716 cells. Insulin release from isolated pancreatic islets was measured using a radioimmunoassay. Single pancreatic β-cell membrane potentials were recorded using whole-cell current-clamp patches perforated by β-escin. In fasting rats, inhalation of isoflurane led to a decrease in the basal levels of GLP-1 but did not affect insulin and glucose levels. Levels of GLP-1, insulin, and glucose increased after gastric administration of glucose in control rats. However, isoflurane attenuated the glucose-induced increase in GLP-1 and insulin levels and increased plasma glucose levels. In contrast, isoflurane did not affect dipeptidyl peptidase-4 activity before or after gastric glucose loading. Isoflurane (0.35 mM) inhibited GLP-1 release in NCI-H716 cells; this finding was similar to that observed in in vivo studies. In perifusion experiments, isoflurane (0.35 mM) inhibited glucose-induced insulin release, whereas exogenous GLP-1 (10 nM) enhanced insulin release. Importantly, combined administration of isoflurane and GLP-1 enhanced both phases of glucose-induced insulin release to an extent similar to that achieved with GLP-1 alone. Whole-cell patches showed that exposure to GLP-1 (10 nM) led to nearly complete restoration of glucose-stimulated depolarization that had been suppressed by isoflurane (0.35 mM). GLP-1 secretion is impaired during isoflurane anesthesia. However, our study showed that the insulinotropic action of GLP-1 was not affected by isoflurane. Furthermore, exposure to GLP-1 increased the membrane activity of pancreatic β-cells, preventing isoflurane-induced impairment of glucose-induced insulin secretion. These results support the hypothesis that GLP-1-based therapy may be a useful approach for achieving intraoperative glycemic control.


Dexmedetomidine directly inhibits vascular ATP-sensitive potassium channels.

Dexmedetomidine is reported to have an effect on peripheral vasoconstriction; however, the exact mechanisms underlying this process are unclear. In this study, we hypothesized that dexmedetomidine-induced inhibition of vascular ATP-sensitive K(+) (K(ATP)) channels may be associated with this vasoconstriction. To test this hypothesis, we investigated the effects of dexmedetomidine on vascular K(ATP)-channel activity at the single-channel level. We used cell-attached and inside-out patch-clamp configurations to examine the effects of dexmedetomidine on the activities of native rat vascular K(ATP) channels, recombinant K(ATP) channels with different combinations of various inwardly rectifying potassium channels (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor subunits (SUR1, 2A, 2B), and SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit, namely, Kir6.2ΔC36 channels. Dexmedetomidine was observed to inhibit the native rat vascular K(ATP) channels in both cell-attached and inside-out configurations. This drug also inhibited the activity of all types of recombinant SUR/Kir6.0 K(ATP) channels as well as Kir6.2ΔC36 channels with equivalent potency. These results indicate that dexmedetomidine directly inhibits K(ATP) channels through the Kir6.0 subunit.


The involvement of the neurosteroid allopregnanolone in the antihyperalgesic effect of paroxetine in a rat model of neuropathic pain

Paroxetine increases the levels of neurosteroids, such as allopregnanolone (AP), that influence the excitability of the central nervous system by positive allosteric modulation of γ-aminobutyric acid type A receptors. Here, we investigated the role of AP synthesis on the paroxetine-induced antihyperalgesic effect in a rat model of neuropathic pain induced by lumbar spinal nerve ligation (SNL). Subcutaneous administration of paroxetine in SNL rats, dose-dependently decreased the probability of hyperalgesic response and increased AP levels in the spine but not in either brain or serum. Concomitant treatment with an inhibitor of the AP-synthesizing enzyme, finasteride, attenuated the paroxetine-induced antihyperalgesic effect as well as the paroxetine-induced increase in spinal AP levels. Intrathecal injection of exogenous AP mimicked the analgesic effects of paroxetine in vehicle-treated SNL rats, whereas no additional analgesic effects were observed in paroxetine-treated SNL rats. Our findings suggest that the antihyperalgesic effect of paroxetine in a rat neuropathic pain model is AP-mediated. These results also suggest that pharmacological-based therapies targeting AP synthesis might be a promising treatment for neuropathic pain.


Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by painful nerve injury in rats

The neurosteroid allopregnanolone (AP) influences the excitability of the central nervous system by acting as a positive allosteric modulator of γ-aminobutyric acid type A (GABA(A)) receptors. Here, we investigated the role of AP and its therapeutic potential in rats that showed hyperalgesic behavior after undergoing spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of rats that underwent SNL were greater than the corresponding levels in control animals. More importantly, spinal AP levels in hyperalgesic rats were lower than those in the rats that did not develop hyperalgesia following SNL; in contrast, brain AP levels were comparable among these groups. No differences in serum AP levels were observed among the groups. In addition, intrathecal exogenous administration of AP showed the antihyperalgesic effects in hyperalgesic rats after SNL. These findings suggest that changes in spinal AP biosynthesis are involved in the pathogenesis of neuropathic pain following peripheral nerve injury, and pharmacological manipulation of this phenomenon may provide a potential therapeutic target for neuropathic pain.


Effects of aging on isoflurane-induced and protein kinase A-mediated activation of ATP-sensitive potassium channels in cultured rat aortic vascular smooth muscle cells.

Isoflurane activates protein kinase A (PKA) in vascular smooth muscle cells (VSMCs), which in turn activates ATP-sensitive potassium (K(ATP)) channels and causes vasodilation. The present study was undertaken to examine whether advanced age influences the effect of isoflurane on K(ATP) channel activity in cultured VSMCs. We used VSMCs obtained from 12- to 15-week-old (adult) and 24- to 25-month-old (aged) male Wistar rats. Electrophysiological experiments were performed using cell-attached and inside-out patch-clamp techniques to monitor the K(ATP) channel activity. Application of isoflurane or forskolin to the bath solution in cell-attached recordings induced a significant increase in K(ATP) channel activity in the VSMCs from the adult group. However, K(ATP) channel opening induced by isoflurane, but not forskolin, was significantly suppressed by aging. On the other hand, cell-free recordings showed similar pharmacologic sensitivity to the K(ATP) channel opener pinacidil, inward rectification, and unitary conductance (40 45 pS) between groups. In addition, direct K(ATP) channel activation by c-PKA in the inside-out patches was similar in both groups. Furthermore, increasing PKA activation in cell-attached patches by CPT-cAMP restored isoflurane's effects in the aged group. These results suggest that aging decreases isoflurane-induced PKA activation, resulting in attenuation of K(ATP) channel opening.


Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle.

Nicorandil opens adenosine triphosphate-sensitive potassium (K(ATP)) channels in the cardiovascular system and is being increasingly used for the treatment of angina pectoris. In the present study, we tested whether intravenous anesthetic agent ketamine affected nicorandil-induced native vascular K(ATP) channel activation.

The Journal of Medical Investigation : JMI


A retrospective survey of conscious sedation used in children undergoing oral surgery or dental treatment during e ten-year period at the Tokushima University Hospital

小児患者の精神鎮静法に関する過去10年間の検討

Journal of Japanese Dental Society of Anesthesiology


Effects of dopamine on ATP-sensitive potassium channels in porcine coronary artery smooth-muscle cells

Dopamine is reported to be a coronary vasodilator; however, the exact mechanism of dopamine action in the coronary circulation remains unclear. In this study, we hypothesized that dopamine-induced activation of coronary ATP-sensitive potassium (KATP) channels may be associated with coronary vasodilation. We therefore investigated the direct effects of dopamine on coronary KATP-channel activity. We used patch-clamp configurations to investigate the effects of dopamine on coronary KATP-channel activity. Application of dopamine (10 to 10 M) to the bath solution during cell-attached recordings induced a concentration-dependent increase in KATP-channel activity. In contrast, dopamine failed to activate KATP channels in inside-out patches. Dopamine-induced coronary KATP-channel currents in cell-attached patches were inhibited by pretreatment with the selective D1-like antagonist, Sch-23390, but they were not influenced by the selective D2-like antagonist, domperidone, or the beta-adrenergic receptor antagonist, propranolol. The selective D1-like agonist, SKF-38393, and the adenylyl cyclase activator, forskolin, mimicked the dopamine effects on coronary KATP channels. Furthermore, pretreatment with an inhibitor of protein kinase A, Rp-cAMPS, abolished the dopamine-induced KATP-channel activation. This study demonstrates that dopamine activates coronary KATP channels via signal transduction involving the D1-like dopaminergic receptor-protein kinase A-signaling pathway.


Effects of prostaglandin E1 on vascular ATP-sensitive potassium channels.

BACKGROUND: Prostaglandin E1 (PGE1) has been reported to activate ATP-sensitive potassium (KATP) channels, which induces vasorelaxation. However, direct evidence of PGE1 interactions with vascular KATP channels is limited. METHODS: The present study investigated the effects and mechanisms of PGE1 on vascular KATP channels in both isometric tension and patch clamp experiments.Isometric tension experiments were performed in rat thoracic aortic rings without an endothelium. Electrophysiologic experiments were performed using patch-clamp techniques to monitor KATP channels in rat vascular smooth muscle cells. RESULTS: PGE1 significantly decreased the isometric tension in a concentration-dependent manner, which was partially inhibited by pretreating with a KATP channel inhibitor, glibenclamide (1 microM), or an inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). Application of PGE1 to the bath solution during cell-attached recordings induced a significant increase in KATP channel activity, whereas PGE1 failed to activate KATP channels in the inside-out patches. The PGE1-induced KATP channel currents in cell-attached patches were abolished by pretreating with Rp-cAMPS (100 microM). CONCLUSIONS: The results indicate that the activation of vascular KATP channels played an important role in the PKA-dependent PGE1-induced vasorelaxation. Furthermore, an electrophysiological experiment demonstrated that PGE1 activated vascular KATP channels via PKA activation.


[Anesthetic management of a teenage athlete who developed arrhythmia during general anesthesia].

全身麻酔時に不整脈を呈した高校生スポーツ選手の麻酔経験

A 17-year-old man with fracture of the mandible underwent open fixation under general anesthesia. He was an athlete of the rugby suffering the fracture in a match. His preoperative physical examinations were normal except for I degrees atrioventricular block on electrocardiogram (ECG). During anesthesia, atrioventricular dissociation and frequent premature ventricular contractions were induced by the stimulation of nasotracheal intubation and the administration of atropine for the reversal of muscle relaxation. We thought the cause of the arrhythmia is the athlete's heart which may be vagotonic and may induce vagal reflex or fatal arrhythmia. This case demonstrates that it is necessary to pay attention to chronotropic action associated with the intubation of nasopharynx, the handling of laryngoscope and the usage of drugs for the anesthetic management of the athlete.


Effects of Propofol and Thiamylal on Nicorandil Induced ATP-sensitive Potassium Channel Activities in Cultured Rat Aortic Smooth Muscle Cells

ニコランジルによる培養ラット血管平滑筋細胞のATP感受性Kチャネル活性に及ぼすプロポフォールとチアミラールの影響

Nicorandil, a hybrid ATP-sensitive potassium (K(ATP)) channel opener and nitrate compound, is used clinically for the treatment of angina pectoris. In the present study, we investigated the effects of propofol and thiamylal on sarcolemmal K(ATP) channels activities induced by nicorandil in cultured rat aortic smooth muscle cells. We used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on nicorandil induced K(ATP) channel activities. K(ATP) channel was not spontaneously activated by patch excision in the absence of intracellular ATP. Application of nicorandil (100 microM) induced a marked activation of KATP channel currents, which was completely blocked by 3 microM glibenclamide, the sulfonylurea that blocks K(ATP) channels. Nicorandil induced KATP channel currents were not significantly inhibited by application of 10 and 100 microM propofol to intracellular surface. However, application of 100 and 300 microM thiamylal to intracellular surface significantly inhibited the nicorandil induced K(ATP) channel currents, with relative channel activities decreasing to 0.65 +/- 0.08 and 0.46 +/- 0.10 of control, respectively. Propofol had no effect on nicorandil induced sarcolemmal KATP channel activities in rat aortic smooth muscle cells, whereas thiamylal significantly inhibited these channel activities at clinically relevant concentrations.


低カリウム血症により心電図異常を認めた糖尿病患者の1例

低カリウム血症により心電図異常を認めた糖尿病患者の1例


Anaesthetic Study for the Management of Body Fluid and the Efficiency of Preoperative Blood Preparation in Orthognathic Surgery During 10 Years

過去10年間の外科的矯正手術における体液管理と輸血準備の効率化についての検討


全内臓逆位を伴った右胸心患者の全身麻酔経験

全内臓逆位を伴った右胸心患者の全身麻酔経験


Extracellular matrix formed by MC3T3-E1 osteoblast-like cells cultured on titanium 2. Collagen fiber formation

Many aspects of the structures formed between titanium and cells and the mechanism of the formation are still unknown. In order to clarify these issues, we analyzed the initial structures formed between titanium and MC3T3-E1 osteoblast-like cells cultured on titanium. The present results indicate that extracellular matrix containing collagen fibers formed at the surface of a calcined layer on the titanium. At first, a hemispherical body and a small secondary spherical structure formed at the surface, followed by more beads to form a string-of-beads structure. These string-of-beads collagen structures elongated and formed spirals. For the first time ever, we directly observed the structure of collagen fiber formed between cultured osteoblasts and titanium with microscopy. Here, we describe the formation mechanism of type I collagen fibers in extracellular bone matrix. Elucidation of the mechanism of collagen fiber formation will aid in the development of controlled tissue regeneration.


Extracellular matrix formed by MC3T3-E1 osteoblast-like cells cultured on titanium 1. Anchor structure

In order to clarify the structure of the extracellular matrix formed by osteoblasts in contact with titanium, we analyzed the structure formed by cultured clonal MC3T3-E1 osteoblasts on a calcified surface of commercial pure titanium, after exfoliating the cells from the surface of the titanium. Collagen fibers formed between neighboring cells and between cells and titanium, in the latter case with one tip of each collagen fiber bound to the cell and the other tip bound to the surface of the titanium embedded in the calcified layer. We called this structure an "anchor structure", because the collagen fibers embedded in the calcified layer anchor the cells to the titanium. This structure may be a reason for the useful biocompatibility between titanium and bone.


General Anaesthetic Management of Super Aged Who was Operated Twice during Two Months : A Case Report

2ヶ月で2度，全身麻酔を受けた超高齢者の1例


Postoperative Pain Management with Continuous Intravenous Infusion of Fentanyl and Propofol in a Pediatric Patient with Mental Retardation:a Case Report

フェンタニルとプロポフォールの持続静脈内投与で術後管理を行った精神発達遅滞を伴う小児患者の1例


Clinico-statistical Observations of Outpatients for Dental Treatment at the Anesthetic Clinic in the Hospital of Tokushima University during a 17-year Period

徳島大学歯学部付属病院歯科麻酔科外来における過去17年間の臨床統計的観察

Journal of Japanese Dental Society of Anesthesiology


徳島大学歯学部附属病院歯科麻酔外来における過去17年間の臨床統計的観察

徳島大学歯学部附属病院歯科麻酔外来における過去17年間の臨床統計的観察


Sturge-Weber 症候群患者の精神鎮静法経験

Sturge-Weber 症候群患者の精神鎮静法経験


リドカインの味覚刺激の種類についての検討

リドカインの味覚刺激の種類についての検討

第28回 日本歯科麻酔麻酔学会総会

第28回 日本歯科麻酔麻酔学会総会


Usefulness of NAZORCAP(TM) during intravenous sedation with propofol in dentistry

歯科治療時の静脈内鎮静法における呼気ガスサンプリングチューブNAZORCAPTM の有用性


Elimination of hypersensitive gagging reaction to dentistry by propofol at subhypnotic doses


Effects of Midazolam and Flumazenil on Reflex Potentials of the Hypoglossal Nerve Evoked by Stimulation of the Palate