Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits. METHODS: Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5 mg/kg droperidol bolus followed by continuous infusion at 5 mg/kg/h, those in the low-dose group received a 0.5 mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3 °C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering. RESULTS: The shivering thresholds in the control, high-dose, and low-dose groups were 38.1 °C ± 1.1 °C, 36.7 °C ± 1.2 °C, and 36.9 °C ± 1.0 °C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups. CONCLUSIONS: Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.

DOI： 10.1007/s00540-023-03240-1

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

BackgroundPostoperative pain and inflammation are significant complications following surgery. Strategies that aim to prevent excessive inflammation without hampering natural wound-healing are required for the management of postoperative pain and inflammation. However, the knowledge of the mechanisms and target pathways involved in these processes is lacking. Recent studies have revealed that autophagy in macrophages sequesters pro-inflammatory mediators, and it is therefore being recognized as a crucial process involved in regulating inflammation. In this study, we tested the hypothesis that autophagy in macrophages plays protective roles against postoperative pain and inflammation and investigated the underlying mechanisms.MethodsPostoperative pain was induced by plantar incision under isoflurane anesthesia in mice lacking macrophage autophagy (Atg5flox/flox LysMCre +) and their control littermates (Atg5flox/flox). Mechanical and thermal pain sensitivity, changes in weight distribution, spontaneous locomotor activity, tissue inflammation, and body weight were assessed at baseline and 1, 3, and 7 days after surgery. Monocyte/macrophage infiltration at the surgical site and inflammatory mediator expression levels were evaluated.ResultsAtg5flox/flox LysMCre + mice compared with the control mice exhibited lower mechanical and thermal pain thresholds and surgical/non-surgical hindlimb weight-bearing ratios. The augmented neurobehavioral symptoms observed in the Atg5flox/flox LysMCre + mice were associated with more severe paw inflammation, higher pro-inflammatory mediator mRNA expression, and more monocytes/macrophages at the surgical site.ConclusionThe lack of macrophage autophagy augmented postoperative pain and inflammation, which were accompanied by enhanced pro-inflammatory cytokine secretion and surgical-site monocyte/macrophage infiltration. Macrophage autophagy plays a protective role in postoperative pain and inflammation and can be a novel therapeutic target.

DOI： 10.1186/s12974-023-02795-w

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PubMed

Authorship：Lead author,　Corresponding author   Language：Japanese  

Authorship：Corresponding author   Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

The lack of sensitive and robust behavioral assessments of pain in preclinical models has been a major limitation for both pain research and the development of novel analgesics. Here, we demonstrate a novel data acquisition and analysis platform that provides automated, quantitative, and objective measures of naturalistic rodent behavior in an observer-independent and unbiased fashion. The technology records freely behaving mice, in the dark, over extended periods for continuous acquisition of 2 parallel video data streams: (1) near-infrared frustrated total internal reflection for detecting the degree, force, and timing of surface contact and (2) simultaneous ongoing video graphing of whole-body pose. Using machine vision and machine learning, we automatically extract and quantify behavioral features from these data to reveal moment-by-moment changes that capture the internal pain state of rodents in multiple pain models. We show that these voluntary pain-related behaviors are reversible by analgesics and that analgesia can be automatically and objectively differentiated from sedation. Finally, we used this approach to generate a paw luminance ratio measure that is sensitive in capturing dynamic mechanical hypersensitivity over a period and scalable for high-throughput preclinical analgesic efficacy assessment.

DOI： 10.1097/j.pain.0000000000002680

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: With recent advances in robot-assisted techniques, an increasing number of surgeries are being performed with pneumoperitoneum and head-down maneuver (HDM) that may affect the cerebral microcirculation. For the first time, this study investigated the direct influence of pneumoperitoneum and HDM on the cerebral microvasculature in rabbits. METHODS: Adult male rabbits were randomly allocated to the following groups (n = 7 each): control, pneumoperitoneum alone (P), and pneumoperitoneum with HDM (P + HDM) for 120 min. A closed cranial window was installed above the parietal bone to visualize the pial microvasculature. Pial arteriolar diameter and hemodynamic and blood gas parameters were measured during the 140-min observation period. Brain edema was assessed by evaluation of the brain water content at the end of the experiment. RESULTS: Rabbits in the P and P + HDM groups exhibited a similar degree of immediate pial arteriolar dilation following the initiation of both P and P + HDM (P: 1.11 ± 0.03, p = 0.0044 and P + HDM: 1.07 ± 0.02, p = 0.0004, relative changes from the baseline value by defining the baseline as one). In the P + HDM group, pial arteriole diameter returned to the baseline level following the discontinuation of pneumoperitoneum and HDM (1.05 ± 0.03, p = 0.0906, vs. baseline). In contrast, the pial arterioles remained dilated as compared to the baseline level in the P group after discontinuation of pneumoperitoneum. There were no changes in pial arteriole diameter in the animals in the control group. Heart rate, blood gas parameters, and brain water content were not significantly different between the groups. CONCLUSION: The pial arterioles dilated immediately after pneumoperitoneum with or without HDM. The pial arterioles remained dilated 20 min after discontinuation of pneumoperitoneum alone but constricted upon discontinuation of pneumoperitoneum plus HDM. Pneumoperitoneum and HDM for 2 h did not cause brain edema.

DOI： 10.1186/s12871-022-01911-2

PubMed

Authorship：Corresponding author   Language：English  

Authorship：Corresponding author   Language：English  

Language：English  

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels.

DOI： 10.3389/fphar.2022.872477

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：DE GRUYTER POLAND SP Z O O  

Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 +/- 2.7 vs 15.7 +/- 2.0 mm(3) at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 +/- 0.23 vs 1.00 +/- 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 +/- 3.1 vs 25.1 +/- 4.7 cells/0.1 mm(2)). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.

DOI： 10.1515/tnsci-2022-0238

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PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1 mg/kg/h), or remimazolam + flumazenil, a selective γ-aminobutyric acid (GABA) type A receptor antagonist (n = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water via a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1 mg/kg/h significantly lowered the core temperature change during shivering (-2.50 ± 0.20°C vs. control: -1.00 ± 0.12°C, p = 0.0009). The effect of 1 mg/kg/h remimazolam on the core temperature change was abolished by flumazenil administration (-0.94 ± 0.16°C vs. control: -1.00 ± 0.12°C, p = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits via the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia.

DOI： 10.3389/fphar.2022.1019114

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND PURPOSE: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough. EXPERIMENTAL APPROACH: We tested the ability of BW-031 to inhibit pain in three models of tissue inflammation:- inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. KEY RESULTS: BW-031 inhibited Nav 1.7 and Nav 1.1 channels with approximately sixfold greater potency than QX-314 when introduced inside cells. BW-031 inhibited inflammatory pain in all three models tested, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was effective in reducing cough counts by 78%-90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization. CONCLUSION AND IMPLICATIONS: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW-031 can also effectively inhibit cough in a guinea pig model of citric acid-induced cough, suggesting a new clinical approach to treating cough.

DOI： 10.1111/bph.15531

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：(MISC) Summary of the papers read (international conference)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

As the world is rapidly aging, and the number of elderly patients who undergo surgery is rising, postoperative cognitive decline among those patients has become an increasing healthcare problem. Although understanding the risk factors and mechanisms underlying the pathogenesis of postoperative cognitive decline is critically important from a preventative viewpoint, such knowledge and evidence are lacking. A growing body of evidence suggest an association between cognitive function and sleep duration. The purpose of this study was to investigate the association between postoperative cognitive function and sleep duration on the night before surgery using a wearable sleep tracker. In this 6-month prospective cohort study, we analyzed data from 194 patients aged ≥ 65 years who underwent elective non-cardiac and non-cranial surgery under general anesthesia. According to the sleep duration on the night before surgery, patients were categorized into following four groups: <5, 5-7, 7-9, and >9 h. Perioperative cognitive function and domains were assessed using a neuropsychological test battery, and the incidence and prevalence of cognitive decline over 6 months after surgery were analyzed using the multiple logistic regression analysis. During the 6-month follow-up period, 41 patients (21%) developed cognitive decline. The incidence of cognitive decline was significantly elevated for the patients with sleep duration < 5 h (vs. 7-9 h; surgical duration-adjusted odds ratio, 3.50; 95% confidence interval, 1.20-10.2; P < 0.05). The association between sleep duration and prevalence of cognitive decline was limited to the early postoperative period (at 1 week and 1 month). Among the cognitive domains assessed, attentional function was significantly impaired in patients with a sleep duration < 5 h [vs. 7-9 h at 1 week; 4/37 (10.8%) vs. 0/73 (0%); P < 0.05]. In conclusion, sleep duration < 5 h on the night before surgery was significantly associated with worse attentional function after surgery and higher incidence of cognitive decline. The present results indicate that sleep deprivation on the night before surgery may have a temporary but significantly negative influence on the patient's postoperative cognitive function and is a potential target for preventing cognitive decline.

DOI： 10.3389/fnagi.2021.821425

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background Although recent studies using experimental models of ischemic brain injury indicate that systemically-administered beta(1)-blockers have potential protective effects on the cerebrovascular system, the precise mechanisms remain unclear. In addition to their cardiovascular effects, water-soluble beta(1)-blockers can pass the blood-brain barrier and may exert their vascular action on cerebral microvessels. The aim of this study was to investigate the direct effects of beta(1)-blockade on the cerebral microvasculature both in the normal state and ischemia/reperfusion state using the cranial window method. Methods The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in adult male rabbits. In the first experiment, various concentrations of the selective beta(1)-blocker landiolol were administered into the cranial window to evaluate the dose-response. In the second experiment, the effect of beta(1)-blockade on the brain during ischemic/reperfusion injury was investigated. Global brain ischemia/reperfusion was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Either landiolol or artificial cerebrospinal fluid was infused 5 min after initiation of ischemia through 120 min after reperfusion. Pial arteriole diameter and hemodynamic and physiological parameters were recorded before ischemia, during ischemia, and 5, 10, 20, 40, 60, 80, 100, and 120 min after reperfusion. Results In the first experiment, topical administration of landiolol at higher concentrations produced slight pial arteriole dilation (10(- 8) mol/L: 4.3 +/- 3.4%, 10(- 6) mol/L: 8.0 +/- 5.8%, 10(- 4) mol/L: 7.3 +/- 4.0%). In the second experiment, the topical administration of landiolol significantly dilated the pial arteriole diameters during ischemia/reperfusion injury (ischemia: 30.6 +/- 38.6%, 5 min: 47.3 +/- 42.2%, 10 min: 47.8 +/- 34.2%, 20 min: 38.0 +/- 39.0%). There were no statistical differences in hemodynamic and physiological parameters between the landiolol and control groups. Conclusions The blockade of beta(1)-adrenergic receptors induced significant vasodilation of pial arterioles during ischemia/reperfusion injury. By contrast, only a slight dilation of the arterioles was observed in the normal state, indicating that ischemic cerebral microvessels are more susceptible to the vasodilatory effect induced by selective blockade of beta(1)-adrenergic receptors than normal microvessels.

DOI： 10.1186/s40360-020-0394-7

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The purpose of this study was to quantitatively investigate light sensitivity asymmetry both between left and right eyes and between upper and lower quadrant in the 30-degree visual field of patients with visual field defects caused by pituitary adenoma. PATIENTS AND METHODS: Preoperative Humphrey 30-2 perimetry results were reviewed retrospectively using the charts of 28 pituitary adenoma patients who underwent surgery. Inter-eye light sensitivity comparisons of the temporal and nasal hemifields between the left and right eyes were conducted in each patient to study left-right asymmetry. Upper-lower asymmetry was investigated by comparing the frequency of severe scotoma (light sensitivity 5 dB or less) in the upper and lower visual field quadrants in the temporal and nasal hemifields. RESULTS: Left-right asymmetry was demonstrated in 61% of cases in the temporal hemifield and in 57% of cases in the nasal hemifield. Severe scotoma test points were investigated in the worse eye of each patient and were more frequent in the superotemporal quadrant of the visual field compared with the inferotemporal quadrant (P = 0.00029) and in the inferonasal quadrant compared to the superonasal quadrant (P = 0.00268). CONCLUSION: Asymmetric visual field defects between left and right eyes are common in patients with pituitary adenoma. Severe scotoma is more frequent in the upper quadrant of the temporal hemifield and in the lower quadrant of the nasal hemifield.

DOI： 10.2147/OPTH.S234422

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC  

Background Sodium ion transportation plays a crucial role in the pathogenesis of hypoxic-ischemic brain injury. Amiodarone, a Vaughan-Williams class III antiarrhythmic drug, has been widely used to treat life-threatening arrhythmia and cardiac arrest worldwide. In addition to its inhibitory effects on the potassium channel, amiodarone also blocks various sodium ion transporters, including the voltage-gated sodium channel, sodium pump, and Na+/Ca+ exchanger. Considering these pharmacological profile, amiodarone may affect the influx-efflux balance of sodium ion in the hypoxic-ischemic brain. Previous studies suggest that the blockade of the voltage-gated sodium channel during hypoxic-ischemic brain injury exerts neuroprotection. On the contrary, the blockade of sodium pump or Na+/Ca+ exchanger during hypoxia-ischemia may cause further intracellular sodium accumulation and consequent osmotic cell death. From these perspectives, the effects of amiodarone on sodium ion balance on the hypoxic-ischemic brain can be both protective and detrimental depending on the clinical and pathophysiological conditions. In this study, we therefore investigated the effect of amiodarone on hypoxic-ischemic brain injury using a murine experimental model. Results Compared with the control group mice, mice that received amiodarone after induction of 40-min hypoxic-ischemic brain injury exhibited lower survival rates over 7 days and worse neurological function. After 25-min hypoxic-ischemic brain injury, amiodarone treated mice exhibited larger infarct volumes (16.0 +/- 6.9 vs. 24.2 +/- 6.8 mm(3), P < 0.05) and worse neurological function. In addition, the brains harvested from the amiodarone-treated mice contained larger amounts of sodium (194.7 +/- 45.1 vs. 253.5 +/- 50.9 mEq/kg dry weight, P < 0.01) and water (259.3 +/- 8.9 vs. 277.2 +/- 12.5 mg, P < 0.01). There were no significant differences in hemodynamic parameters between groups. Conclusions Amiodarone exacerbated brain injuries and neurological outcomes after hypoxic-ischemic insults. Severe brain sodium accumulation and brain edema were associated with the detrimental effects of amiodarone. Amiodarone at the clinical dose can exacerbate brain injury after hypoxic-ischemic insult by affecting sodium ion transportation and facilitate intracellular sodium accumulation in the brain.

DOI： 10.1186/s12868-019-0544-2

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Voltage-dependent sodium and calcium channels in pain-initiating nociceptor neurons are attractive targets for new analgesics. We made a permanently charged cationic derivative of an N-type calcium channel-inhibitor. Unlike cationic derivatives of local anesthetic sodium channel blockers like QX-314, this cationic compound inhibited N-type calcium channels more effectively with extracellular than intracellular application. Surprisingly, the compound is also a highly effective sodium channel inhibitor when applied extracellularly, producing more potent inhibition than lidocaine or bupivacaine. The charged inhibitor produced potent and long-lasting analgesia in mouse models of incisional wound and inflammatory pain, inhibited release of the neuropeptide calcitonin gene-related peptide (CGRP) from dorsal root ganglion neurons, and reduced inflammation in a mouse model of allergic asthma, which has a strong neurogenic component. The results show that some cationic molecules applied extracellularly can powerfully inhibit both sodium channels and calcium channels, thereby blocking both nociceptor excitability and pro-inflammatory peptide release.

DOI： 10.7554/eLife.48118

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Language：English   Publishing type：Research paper (scientific journal)  

Blood vessels in the CNS form a specialized and critical structure, the blood-brain barrier (BBB). We present a resource to understand the molecular mechanisms that regulate BBB function in health and dysfunction during disease. Using endothelial cell enrichment and RNA sequencing, we analyzed the gene expression of endothelial cells in mice, comparing brain endothelial cells with peripheral endothelial cells. We also assessed the regulation of CNS endothelial gene expression in models of stroke, multiple sclerosis, traumatic brain injury and seizure, each having profound BBB disruption. We found that although each is caused by a distinct trigger, they exhibit strikingly similar endothelial gene expression changes during BBB disruption, comprising a core BBB dysfunction module that shifts the CNS endothelial cells into a peripheral endothelial cell-like state. The identification of a common pathway for BBB dysfunction suggests that targeting therapeutic agents to limit it may be effective across multiple neurological disorders.

DOI： 10.1038/s41593-019-0497-x

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Ischemic-hypoxic insult leads to detrimental effects on multiple organs. The brain is especially vulnerable, and it is hard to regenerate once damaged. Currently, therapeutic options are very limited. Previous studies have reported neuroprotective effects of neurotropin, a non-protein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, using a murine model of peripheral nerve injury and cultured cell lines. However, whether neurotropin might have protective effects against brain injuries remains unclear. We, therefore, investigated the neuroprotective effect of neurotropin and possible underlying mechanisms, using a mouse model of hypoxic-ischemic brain injury. METHODS: Hypoxic-ischemic brain injury was induced via a combination of the left common carotid artery occlusion and exposure to hypoxic environment (8% oxygen) in adult male C57BL/6 mice. Immediately following induction of hypoxia-ischemia, mice received either saline or 2.4 units of neurotropin. The survival rate, neurological function, infarct volume, and expression of inflammatory cytokines were evaluated. RESULTS: Compared to the control group, the neurotropin group exhibited a significantly higher survival rate (100% vs. 62.5%, p < 0.05) and lower neurological deficit scores (1; 0-2 vs. 3; 0-5, median; range, p < 0.05) after the hypoxic-ischemic insult. The administration of neurotropin also reduced infarct volume (18.3 ± 5.1% vs. 38.3 ± 7.2%, p < 0.05) and mRNA expression of pro-inflammatory cytokines. CONCLUSIONS: The post-treatment with neurotropin improved survival and neurological outcomes after hypoxic-ischemic insult. Our results indicate that neurotropin has neuroprotective effects against hypoxic-ischemic brain injury by suppressing pro-inflammatory cytokines.

DOI： 10.1007/s00540-019-02655-z

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Purpose: Although amiodarone is classified as a Vaughan-Williams class Ⅲ antiarrhythmic drug, it has inhibitory effects on voltage-gated sodium and calcium channels and on β-adrenergic receptors. Given these pharmacological profiles, amiodarone may have analgesic properties. Most patients who are prescribed amiodarone possess multiple cardiovascular risk factors. Despite the fact that pain plays a crucial role as a clinical indicator of cardiovascular events, the effects of amiodarone on pain have not been investigated. The aim of the current study was to investigate the analgesic effects of amiodarone by using mouse models of pain in an effort to elucidate underlying mechanisms. Methods: Adult male C57B6 mice received single bolus intraperitoneal injections of amiodarone at doses of 25, 50, 100, and 200 mg/kg, while the mice in the control group received only normal saline. The analgesic effects of amiodarone were evaluated using the acetic acid-induced writhing test, formalin test, and tail withdrawal test. In addition, the potassium channel opener NS1643, voltage-gated sodium channel opener veratrine, calcium channel opener BAYK8644, and selective β-adrenergic agonist isoproterenol were used to uncover the underlying mechanism. Results: During the acetic acid-induced writhing test, formalin test, and tail withdrawal test, amiodarone induced analgesic responses in a dose-dependent manner. The analgesic effects of amiodarone were abolished by veratrine but not by NS1643, BAYK8644, or isoproterenol. Conclusion: Amiodarone induced analgesic responses in a dose-dependent manner, likely by blocking voltage-gated sodium channels. These results indicate that clinical doses of amiodarone can affect nociception and may mask or attenuate pain induced by acute cardiovascular events.

DOI： 10.2147/JPR.S196480

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Involuntary muscle contraction caused by extracardiac stimulation is a rare complication induced by a pacemaker. We report a case who developed sudden onset diaphragmatic contractions during general anesthesia caused by a DDD mode pacemaker. CASE PRESENTATION: A 74-year-old woman with a permanent pacemaker was scheduled to undergo mastectomy. The pacing mode was switched from DDD to VOO intraoperatively to avoid electromagnetic interference. Immediately after returning the pacing mode to DDD after surgery, diaphragmatic contractions occurred, mimicking bucking type of movements. After switching the pacing to A-sense V-pace, the twitching ceased. Because no structural problems were noted, and the twitching disappeared after terminating atrial pacing, diaphragmatic contractions might be caused by stimulation of the right phrenic nerve located near the right appendage where the electrode was installed. CONCLUSION: The potential risk of muscle twitching should be carefully evaluated preoperatively especially in patients with atypical position of pacemaker leads.

DOI： 10.1186/s40981-019-0257-7

PubMed

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: We evaluated the change of cerebral regional tissue oxygen saturation (rSO2) along with the pneumoperitoneum and the Trendelenburg position. We also assessed the relationship between the change of rSO2 and the changes of mean arterial blood pressure (MAP), heart rate (HR), arterial carbon dioxide tension (PaCO2), arterial oxygen tension (PaO2), or arterial oxygen saturation (SaO2). METHODS: Forty-one adult patients who underwent a robotic assisted endoscopic prostatic surgery under propofol and remifentanil anesthesia were involved in this study. During the surgery, a pneumoperitoneum was established using carbon dioxide. Measurements of rSO2, MAP, HR, PaCO2, PaO2, and SaO2 were performed before the pneumoperitoneum (baseline), every 5 min after the onset of pneumoperitoneum, before the Trendelenburg position. After the onset of the Trendelenburg position, rSO2, MAP, HR were recorded at 5, 10, 20, 30, 45, and 60 min, and PaCO2, PaO2, and SaO2 were measured at 10, 30, and 60 min. RESULTS: Before the pneumoperitoneum, left and right rSO2 were 67.9 ± 6.3% and 68.5 ± 7.0%. Ten minutes after the onset of pneumoperitoneum, significant increase in the rSO2 was observed (left: 69.6 ± 5.9%, right: 70.6 ± 7.4%). During the Trendelenburg position, the rSO2 increased initially and peaked at 5 min (left: 72.2 ± 6.5%, right: 73.1 ± 7.6%), then decreased. Multiple regression analysis showed that change of rSO2 correlated with MAP and PaCO2. CONCLUSIONS: Pneumoperitoneum and the Trendelenburg position in robotic-assisted endoscopic prostatic surgery did not worsen cerebral oxygenation. Arterial blood pressure is the critical factor in cerebral oxygenation. TRIAL REGISTRATION: Japan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000026227 (retrospectively registered).

DOI： 10.1186/s12871-019-0736-4

PubMed

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Gut microbiota modulates metabolic and immunoregulatory axes and contributes to the pathophysiology of diseases with inflammatory components, such as atherosclerosis, diabetes mellitus, and ischemic stroke. Inflammation is emerging as a critical player in the pathophysiology of an intracranial aneurysm. Therefore, we hypothesized that the gut microbiota affects aneurysm formation by modulating inflammation. We induced intracranial aneurysms in mice by combining systemic hypertension and a single injection of elastase into the cerebrospinal fluid. Depletion of the gut microbiota was achieved via an oral antibiotic cocktail of vancomycin, metronidazole, ampicillin, and neomycin. Antibiotics were given 3 weeks before aneurysm induction and either continued until the end of the experiment or stopped 1 day before aneurysm induction. We also assessed the effects of the gut microbiota depletion on macrophage infiltration and mRNA levels of inflammatory cytokines. Gut microbiota depletion by antibiotics reduced the incidence when antibiotics were started 3 weeks before aneurysm induction and continued until the end of the experiment (83% versus 6%, P<0.001). Even when antibiotics were stopped 1 day before aneurysm induction, the gut microbiota depletion significantly reduced the incidence of aneurysms (86% versus 28%, P<0.05). Both macrophage infiltration and mRNA levels of inflammatory cytokines were reduced with gut microbiota depletion. These findings suggest that the gut microbiota contributes to the pathophysiology of aneurysms by modulating inflammation. Human studies are needed to determine the exact contribution of the gut microbiota to the pathophysiology of aneurysm formation and disease course in humans.

DOI： 10.1161/HYPERTENSIONAHA.118.11804

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Ion channels play a crucial role in the development of ischemic brain injury. Recent studies have reported that the blockade of various types of ion channels improves outcomes in experimental stroke models. Amiodarone, one of the most effective drugs for life-threatening arrhythmia, works as a multiple channel blocker and its characteristics cover all four Vaughan-Williams classes. Although it is known that amiodarone indirectly contributes to preventing ischemic stroke by maintaining sinus rhythm in patients with atrial fibrillation, the direct neuroprotective effect of amiodarone has not been clarified. The purpose of this study was to investigate the direct effect of amiodarone on ischemic stroke in mice.
Methods: Focal cerebral ischemia was induced via distal permanent middle cerebral artery occlusion (MCAO) in adult male mice. The amiodarone pre-treatment group received 50 mg/kg of amiodarone 1 h before MCAO; the amiodarone post-treatment groups received 50 mg/kg of amiodarone immediately after MCAO; the control group received vehicle only. In addition, the sodium channel opener veratrine and selective beta-adrenergic agonist isoprotelenol were used to elucidate the targeted pathway. Heart rate and blood pressure were monitored perioperatively. Infarct volume analysis was conducted 48 h after MCAO. The body asymmetry test and the corner test were used for neurological evaluation.
Results: Amiodarone pre-treatment and post-treatment reduced the heart rate but did not affect the blood pressure. No mice showed arrhythmia. Compared with the control group, the amiodarone pre-treatment group had smaller infarct volumes (8.9 +/- 2.1% hemisphere [mean +/- SD] vs. 11.2 +/- 1.4%; P &lt; 0.05) and improved functional outcomes: lower asymmetric body swing rates (52 +/- 17% vs. 65 +/- 18%; P &lt; 0.05) and fewer left turns (7.1 +/- 1.2 vs. 8.3 +/- 1.2; P &lt; 0.05). In contrast, amiodarone post-treatment did not improve the outcomes after MCAO. The neuroprotective effect of amiodarone pre-treatment was abolished by co-administration of veratrine but not by isoproterenol.
Conclusions: Amiodarone pre-treatment attenuated ischemic brain injury and improved functional outcomes without affecting heart rhythm and blood pressure. The present results showed that amiodarone pre-treatment has neuroprotective effects, at least in part, via blocking the sodium channels.

DOI： 10.1186/s12871-017-0459-3

Web of Science

Language：Japanese   Publisher：日本神経麻酔集中治療学会  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：English  

Authorship：Lead author,　Corresponding author   Language：English  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion.
Methods: Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10(-6) mol . L-1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10(-6) mol . L-1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10(-6) mol . L-1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping.
Results: Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5-8% in large arterioles and 11-12% in small arterioles).
Conclusions: Y-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.

DOI： 10.1186/s12871-017-0331-5

Web of Science

Language：English  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUNDNear-infrared spectroscopy estimates cerebral regional tissue oxygen saturation (rSO(2)), which may decrease under hyperventilation. Propofol and sevoflurane act differently on cerebral blood vessels. Consequently, cerebral blood flow during hyperventilation with propofol and sevoflurane anaesthesia may differ.OBJECTIVESThe first aim of this study was to compare the changes in rSO(2) between propofol and sevoflurane anaesthesia during hyperventilation. The second aim was to assess changes in rSO(2) with ventilation changes.DESIGNA randomised, open-label study.SETTINGUniversity of Yamanashi Hospital, Yamanashi, Japan from January 2014 to September 2014.PARTICIPANTSFifty American Society of Anesthesiologists physical status 1 or 2 adult patients who were scheduled for elective abdominal surgery were assigned randomly to receive either propofol or sevoflurane anaesthesia. Exclusion criterion was a known history of cerebral disease such as cerebral infarction, cerebral haemorrhage, transient ischaemic attack and subarachnoid haemorrhage.INTERVENTIONSAfter induction of anaesthesia but before the start of surgery, rSO(2), arterial carbon dioxide partial pressure (PaCO2) and arterial oxygen saturation were measured. Measurements were repeated at 5-min intervals during 15min of hyperventilation with a PaCO2 around 30mmHg (4kPa), and again after ventilation was normalised.MAIN OUTCOME MEASURESThe primary outcome was the difference of changes in rSO(2) between propofol anaesthesia and sevoflurane anaesthesia during and after hyperventilation. The second outcome was change in rSO(2) after the initiation of hyperventilation and after the normalisation of ventilation.RESULTSChanges of rSO(2) during hyperventilation were -107% (left) and -118% (right) in the propofol group, and -10 +/- 8% (left) and -9 +/- 7% (right) in the sevoflurane group. After normalisation of PaCO2, rSO(2) returned to baseline values. Arterial oxygen saturation remained stable throughout the measurement period. The rSO(2) values were similar in the propofol and the sevoflurane groups at each time point.CONCLUSIONThe effects of hyperventilation on estimated rSO(2) were similar with propofol and sevoflurane anaesthesia. Changes in rSO(2) correlated well with ventilation changes.TRIAL REGISTRATIONJapan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000010640

DOI： 10.1097/EJA.0000000000000507

Web of Science

Language：Japanese  

Language：Japanese  

Language：English  

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Lippincott Williams and Wilkins  

BACKGROUND Near-infrared spectroscopy estimates cerebral regional tissue oxygen saturation (rSO2), which may decrease under hyperventilation. Propofol and sevoflurane act differently on cerebral blood vessels. Consequently, cerebral blood flow during hyperventilation with propofol and sevoflurane anaesthesia may differ. OBJECTIVES The first aim of this study was to compare the changes in rSO2 between propofol and sevoflurane anaesthesia during hyperventilation. The second aim was to assess changes in rSO2 with ventilation changes. DESIGN A randomised, open-label study. SETTING University of Yamanashi Hospital, Yamanashi, Japan from January 2014 to September 2014. PARTICIPANTS Fifty American Society of Anesthesiologists physical status 1 or 2 adult patients who were scheduled for elective abdominal surgery were assigned randomly to receive either propofol or sevoflurane anaesthesia. Exclusion criterion was a known history of cerebral disease such as cerebral infarction, cerebral haemorrhage, transient ischaemic attack and subarachnoid haemorrhage. INTERVENTIONS After induction of anaesthesia but before the start of surgery, rSO2, arterial carbon dioxide partial pressure (PaCO2) and arterial oxygen saturation were measured. Measurements were repeated at 5-min intervals during 15 min of hyperventilation with a PaCO2 around 30 mmHg (4 kPa), and again after ventilation was normalised. MAIN OUTCOME MEASURES The primary outcome was the difference of changes in rSO2 between propofol anaesthesia and sevoflurane anaesthesia during and after hyperventilation. The second outcome was change in rSO2 after the initiation of hyperventilation and after the normalisation of ventilation. RESULTS Changes of rSO2 during hyperventilation were - 10 ± 7% (left) and - 11 ± 8% (right) in the propofol group, and - 10 ± 8% (left) and - 9 ± 7% (right) in the sevoflurane group. After normalisation of PaCO2, rSO2 returned to baseline values. Arterial oxygen saturation remained stable throughout the measurement period. The rSO2 values were similar in the propofol and the sevoflurane groups at each time point. CONCLUSION The effects of hyperventilation on estimated rSO2 were similar with propofol and sevoflurane anaesthesia. Changes in rSO2 correlated well with ventilation changes.

DOI： 10.1097/EJA.0000000000000507

Scopus

PubMed

Language：Japanese  

Language：English  

Authorship：Lead author   Language：English  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Rho-kinase inhibitor is widely used for prevention of cerebral vascular spasm. However, the cerebral pial vascular action of Rho-kinase inhibitor has not been investigated. We therefore evaluated the direct effects of Y-27632, a Rho-kinase inhibitor, on pial microvessels.
Experiments were performed on anesthetized rabbits. A closed cranial window was used to visualize the pial microcirculation. After baseline hemodynamic and pial vascular measurements, the cranial window was superfused with four increasing concentrations of Y-27632 (10(-9), 10(-7), 10(-6), 10(-5) mol l(-1); n = 7) dissolved in artificial cerebrospinal fluid for 7 min each. We measured the diameters of pial vessels, mean arterial pressure (MAP), heart rate (HR), and rectal temperature at 7 min after application of each Y-27632 concentration.
MAP, HR, rectal temperature, arterial pH, PaCO2, PaO2, and plasma Na+, K+ and glucose concentrations did not change significantly during the experimental period. Y-27632 at 10(-9) to 10(-7) mol l(-1) did not produce any significant change in pial arterioles. Topical application of Y-27632 at 10(-6) and 10(-5) mol l(-1) produced pial large (8.4 +/- A 5.7 and 19.8 +/- A 12.7 %) and small (10.1 +/- A 8.5 and 18.1 +/- A 12.3 %) arterioles dilation. However, Y-27632 did not produce any change in pial large and small venules.
We evaluated the direct effects of Y-27632 on pial microvessels. Y-27632 dilates only pial arterioles in a concentration-dependent manner, and most at a concentration of 10(-5) mol l(-1). Y-27632 is a potent cerebral pial arteriolar dilator but is not a venular dilator.

DOI： 10.1007/s00540-014-1903-x

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after injection into breast tissue: 40 women had anaesthesia for breast surgery maintained with sevoflurane or propofol (20 randomly allocated to each). Saturations were recorded with a digital pulse oximeter, in arterial blood samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p &lt; 0.0001 for both. The falsely reduced oximeter readings persisted for at least 2 h. The mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p &lt; 0.0001.

DOI： 10.1111/anae.12932

Web of Science

Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Although sevoflurane and propofol are commonly used anesthetics in rabbits, optimal doses of remain unclear. We thus assessed the optimal hypnotic doses of sevoflurane and propofol, and evaluated the influence of dexmedetomidine on sevoflurane and propofol requirements. Methods: Twenty-eight Japanese white rabbits were randomly assigned to one of four groups (n = 7 each). Rabbits were given either sevoflurane, propofol, sevoflurane + dexmedetomidine, or propofol + dexmedetomidine (injected 30 μg?kg-1?hr-1 for 10 min followed by an infusion of 3.5 μg?kg-1?hr-1). Hypnotic level was evaluated with Bispectral Index (BIS), a well-validated electroenchalographic measure, with values between 40 and 60 representing optimal hypnosis. BIS measurements were made 10 minutes after the adjustment of target end-Tidal sevoflurane concentration in the sevoflurane group and sevoflurane + dexmedetomidine group, and at 10 min after the change of infusion rate in the propofol group and propofol + dexmedetomidine group. Results: BIS values were linearly related to sevoflurane concentration and propofol infusion rate, with or without dexmedetomidine. Sevoflurane concentration at BIS = 50 was 3.9 ± 0.2% in the sevoflurane group and 2.6 ± 0.3% in the sevoflurane + dexmedetomidine group. The propofol infusion rate to make BIS = 50 was 102 ± 5 mg?kg-1?hr-1 in the propofol group, and 90 ± 10 mg?kg-1?hr-1 in the propofol + dexmedetomidine group. Conclusions: The optimal end-Tidal concentration of sevoflurane alone was thus 3.9%, and optimal infusion rate for propofol alone was 102 mg?kg-1?hr-1. Dexmedetomidine reduced sevoflurane requirement by 33% and propofol requirement by 11%.

DOI： 10.1186/1756-0500-7-820

Scopus

PubMed

Language：English  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Kokuseido Publishing Co. Ltd  

Background : Femoral nerve block and sciatic nerve block are used to provide intraoperative and postoperative analgesia for total knee arthroplasty. Sciatic nerve block is contraindicated in our hospital, because orthopedists want to assess peroneal nerve function after the surgery. We retrospectively assessed postoperative analgesic effect and complications of the continuous femoral nerve block for total knee arthroplasty. Methods : We included 19 cases in 17 patients scheduled to undergo total knee arthroplasty under femoral nerve block combined with general anesthesia Ultrasound-guided femoral nerve block was performed before the surgery. The ultrasound linear probe was used to visualize the femoral nerve. A 22 gauge needle attached to a nerve stimulator, was inserted with in-plane method. Five percent glucose solution was injected through the needle to encircle the femoral nerve. Then, the 22 gauge needle was withdrawn and an 18 gauge needle was inserted with out-of-plane method. Five percent glucose solution was injected through the needle to confirm the needle tip and perineural catheter was inserted through the needle. To achieve femoral nerve block, 0.375% ropivacaine 20 ml was injected through the needle. Perineural infusion with 0.15% ropivacaine at 4 ml·hr-1 was initiated at the end of the surgery. Intravenous patient-controlled analgesia (IV-PCA) was also conducted postoperatively. We assessed pain at rest with a verbal numeric pain rating score (0-10) including pain on moving, and nausea as well as vomiting. Results : Patients with numeric pain scores at 3 or less were 14 out of 19. Two patients complained of severe pain. There were 4 cases suffering pain on moving. Conclusions : Femoral nerve separation with 5% glucose solution using in-palne method and catheter placement with out-of-plane method could be useful for perineural catheter placement. Perineural infusion of 0.15% ropivacaine at 4 ml·hr-1 combined with IV-PCA provided a good postoperative analgesia in patients receiving total knee arthroplasty.

Scopus

PubMed

Language：English  

Language：English   Publisher：WILEY-BLACKWELL  

DOI： 10.1111/anae.12432

Web of Science

Language：English  

Language：English  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Symposium workshop panel(nominated)  

Event date： 2022.10

Language：English   Presentation type：Poster presentation  

Language：Japanese   Presentation type：Oral presentation(general)  

Event date： 2022.3

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Event date： 2021.11

Language：Japanese   Presentation type：Oral presentation(invited, special)  

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Event date： 2021.5

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Event date： 2018.10

Language：English   Presentation type：Poster presentation  

Venue：San Francisco, CA  

Event date： 2018.10

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Venue：San Francisco, CA  

Event date： 2018.10

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Venue：San Francisco, CA  

Event date： 2018.10

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Venue：San Francisco, CA  

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Venue：San Francisco, CA  

Event date： 2018.9

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Venue：Boston, MA  

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Venue：Boston, MA  

Event date： 2017.10

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Event date： 2016.9

Language：Japanese   Presentation type：Symposium workshop panel(nominated)  

Venue：神奈川県（横浜ベイホテル東急）  

Language：Japanese   Presentation type：Symposium workshop panel(nominated)  

Event date： 2016.9

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：神奈川県（横浜ベイホテル東急）  

Event date： 2016.9

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Event date： 2016.5

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Event date： 2014.9

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Venue：大阪（ホテル阪急エキスポパーク）  

Event date： 2014.8

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Venue：東京（京王プラザホテル）  

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Venue：山梨県中巨摩郡昭和町  

Event date： 2012.9

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Event date： 2012.9

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Event date： 2012.4

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Venue：岡山市（岡山コンベンションセンター）  

Event date： 2011.9

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Venue：大阪（千里ライフサイエンスセンター）  

Event date： 2010.9

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Venue：岡山市（倉敷市芸文館）  

Event date： 2010.9

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Venue：東京（有明TFT）  

Event date： 2009.11

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Venue：長野県諏訪市  

Event date： 2009.9

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Venue：長野県松本  

Event date： 2009.9

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Venue：長野県松本  

Event date： 2008.11

Language：Japanese   Presentation type：Oral presentation(general)  

Venue：山梨県中央市  

Applicant：国立大学法人山梨大学

Application no：特願2022-082600  Date applied：2022.5

Announcement no：特開2023-170685  Date announced：2023.12

J-GLOBAL

Application no：特願2024-097051