Atsuhiro Sakamoto

Nippon Medical School, Edo, Tōkyō, Japan

Are you Atsuhiro Sakamoto?

Claim your profile

Publications (136)240.3 Total impact

  • Source
    Tomonori Morita, Masashi Ishikawa, Atsuhiro Sakamoto
    [Show abstract] [Hide abstract]
    ABSTRACT: Anaesthetic preconditioning (APC) and ischemic preconditioning (IPC) ameliorate liver ischemia-reperfusion (I/R) injury and are important for regulating hepatic I/R injury. MicroRNAs (miRNAs) are short, noncoding RNA molecules of 21-23 nucleotides in length, and are currently under intensive investigation regarding their ability to regulate gene expression in a wide range of species. miRNA activity is involved in controlling a wide range of biological functions and processes. We evaluated whether APC and IPC are mediated by the same miRNAs by performing comprehensive miRNA screening experiments in a rat model of hepatic I/R injury. Twenty-one rats were randomly divided into three groups (n = 7/group): control (mock preconditioning), APC, and IPC. Control rats were subjected to 60 min of hepatic ischemia followed by 4 h of reperfusion, whereas the APC and IPC groups were preconditioned with 2% sevoflurane and hepatic ischemia for 10 min prior to ischemia-reperfusion, respectively. Liver samples were collected to measure miRNA levels after 3 h of reperfusion, and gene networks and canonical pathways were identified using Ingenuity Pathway Analysis (IPA). Blood samples were collected to measure the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Although haemodynamic parameters did not vary among the groups, AST and ALT levels were significantly higher in the control group than in the APC and IPC groups. Comprehensive miRNA screening experiments revealed that most miRNAs altered in the APC group were common to those in the IPC group. IPA identified five miRNAs related to the Akt-glycogen synthase kinase-3β (GSK-3β)-cyclin D1 pathway that were significantly affected by both preconditioning strategies. The application of either APC or IPC to ameliorate hepatic I/R injury results in expression of several common miRNAs that are related to the Akt-GSK-cyclin D1 pathway.
    PLoS ONE 05/2015; 10(5):e0125866. DOI:10.1371/journal.pone.0125866 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Volatile anesthetics have a lung protective effect in acute lung injury (ALI). Our previous study showed sevoflurane affects the expression of microRNA (miRNA) that control various physiological systems by regulating messenger RNA (mRNA) expression. However, the association between the anti-inflammatory effect of sevoflurane and miRNAs modulation remains unknown. The aim of the present study was to investigate the effect of sevoflurane and the expression of miRNAs in an endotoxin-induced ALI model in rats. Wistar rats were randomly assigned to three groups [lipopolysaccharide (LPS), LPS-sevoflurane and control; n=8/group]. All the rats were mechanically ventilated and intravenously-administered LPS (saline as control). Two hours post-injury, general anaesthesia was performed for 4 h with 2% sevoflurane (LPS-sevoflurane). The LPS and the control groups did not receive anaesthesia. The severity of ALI was evaluated by partial pressure of oxygen/fraction of inspired oxygen and the mRNA expression of inflammatory cytokine. The miRNA expression in lung tissue was analyzed by a reverse transcription-quantitative polymerase chain reaction. LPS caused ALI, evidenced by the impairment of pulmonary function and increased mRNA levels of tumor necrosis factor-α, interleukin-6 and nuclear factor-κB. Sevoflurane improved pulmonary function and inhibited the increased mRNAs. Of the 219 miRNAs detected, 15 and nine miRNAs were significantly changed in the LPS and LPS-sevoflurane group, respectively. In the LPS-sevoflurane group, the expression of several miRNAs that regulate inflammation was significantly changed compared to the LPS group. In conclusion, the present data showed that sevoflurane influences the expression of the miRNAs that regulate inflammation. This result suggests that the changes in miRNA expression are involved in the lung protective mechanisms of volatile anesthetics.
    02/2015; 3(3). DOI:10.3892/br.2015.428
  • M Kimura, A Sakai, A Sakamoto, H Suzuki
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and PurposeThe locus coeruleus (LC) is the principal nucleus containing the noradrenergic neurons and is a major endogenous source of pain modulation in the brain. Glial cell line-derived neurotrophic factor (GDNF), a well-established neurotrophic factor for noradrenergic neurons, is a major pain modulator in the spinal cord and primary sensory neurons. However, it is unknown whether GDNF is involved in pain modulation in the LC.Experimental ApproachRats with chronic constriction injury (CCI) of the left sciatic nerve were used as a model of neuropathic pain. GDNF was injected into the left LC of rats with CCI for 3 consecutive days, and changes in mechanical allodynia and thermal hyperalgesia were assessed. The α2-adrenoceptor antagonist yohimbine was intrathecally administered to examine the involvement of descending inhibition in GDNF-mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signaling pathway plays a role in the analgesic effects of GDNF.Key ResultsBoth mechanical allodynia and thermal hyperalgesia were attenuated 24 h after the first GDNF injection. GDNF increased the noradrenaline content in the dorsal spinal cord. The analgesic effects continued for at least 3 days after the last injection. Yohimbine abolished these effects of GDNF. The analgesic effects of GDNF were partially, but significantly, inhibited by prior injection of U0126 into the LC.Conclusions and ImplicationsGDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
    British Journal of Pharmacology 01/2015; 172(10). DOI:10.1111/bph.13073 · 4.99 Impact Factor
  • Source
    Tadashi Okabe, Gentaro Goto, Yoko Hori, Atsuhiro Sakamoto
    [Show abstract] [Hide abstract]
    ABSTRACT: The frequency of malpositioning of gastric tubes in the trachea has been reported to be 0.3-15%, which may cause severe complications, such as pneumonia, if not detected promptly. If a gastric tube can be guided into the esophagus under direct vision with a video laryngoscope, misplacement of the gastric tube into the trachea can be avoided. We compared gastric tube insertion under direct vision using a video laryngoscope with the conventional method of blind insertion.
    BMC Anesthesiology 09/2014; 14:82. DOI:10.1186/1471-2253-14-82 · 1.33 Impact Factor
  • Article: [OPCAB].
    Keiko Nakazato, Atsuhiro Sakamoto
    [Show abstract] [Hide abstract]
    ABSTRACT: Off-pump coronary artery bypass grafting (OPCAB) has some advantages in reduction of postoperative complications including systematic inflammatory response, myocardial injury, renal injury and cerebral injury, compared to on-pump coronary artery bypass grafting. It is important to reduce myocardial oxygen consumption during anesthesia for OPCAB. The anesthesiologists should collaborate with the cardiac surgeons and plan the best perioperative strategy for rapid recovery. The anesthesiologists should pay attention to hemodynamic instability and myocardial ischemia during anastomosis. Fast-track anesthesia offers many benefits which lead to earlier ambulation, earlier discharge and earlier rehabilitation. Further fast-track anesthesia including extubation after OPCAB in the operating room is needed, but can only be performed in selected patients.
    Masui. The Japanese journal of anesthesiology 05/2014; 63(5):506-12.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Postoperative atrial fibrillation (POAF) is one of the most common complications after cardiac surgery. Patients who develop POAF have a prolonged stay in the intensive care unit and hospital and an increased risk of postoperative stroke. Many guidelines for the management of cardiac surgery patients, therefore, recommend perioperative administration of beta-blockers to prevent and treat POAF. Landiolol is an ultra-short acting beta-blocker, and some randomized controlled trials of landiolol administration for the prevention of POAF have been conducted in Japan. This meta-analysis evaluated the effectiveness of landiolol administration for the prevention of POAF after cardiac surgery. The Medline/PubMed and BioMed Central databases were searched for randomized controlled trials comparing cardiac surgery patients who received perioperative landiolol with a control group (saline administration, no drug administration, or other treatment). Two independent reviewers selected the studies for inclusion. Data regarding POAF and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method (fixed effects model). Six trials with a total of 560 patients were included in the meta-analysis. Landiolol administration significantly reduced the incidence of POAF after cardiac surgery (OR 0.26, 95% CI 0.17-0.40). The effectiveness of landiolol administration was similar in three groups: all patients who underwent coronary artery bypass grafting (CABG) (OR 0.27, 95% CI 0.17-0.43), patients who underwent CABG compared with a control group who received saline or nothing (OR 0.28, 95% CI 0.17-0.45), and all patients who underwent cardiac surgery compared with a control group who received saline or nothing (OR 0.27, 95% CI 0.17-0.42). Only two adverse events associated with landiolol administration were observed (2/302, 0.7%): hypotension in one patient and asthma in one patient. Landiolol administration reduces the incidence of POAF after cardiac surgery and is well tolerated.
    Advances in Therapy 04/2014; 31(4). DOI:10.1007/s12325-014-0116-x · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin. The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxin. Two hundred patients with AF/AFL, heart rate (HR) ≥ 120 beats/min, and LV ejection fraction (LVEF) 25-50% were randomized to receive either landiolol (n = 93) or digoxin (n = 107). Successful HR control was defined as ≥20% reduction in HR together with HR < 110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin. The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction. The efficacy in patients with NYHA class III/NYHA class IV was 52.3%/35.3% in landiolol, and 13.8%/9.1% in digoxin (p < 0.001 and p = 0.172), lower LVEF (25-35%)/higher LVEF (35-50%) was 45.7%/51.1% in landiolol, and 14.0%/12.7% in digoxin (p < 0.001 and p < 0.001), CKD stage 1 (90 < eGFR)/CKD stage 2 (60 ≤ eGFR < 90)/CKD stage 3 (30 ≤ eGFR < 60)/CKD stage 4 (15 ≤ eGFR < 30) was 66.7%/59.1%/39.6%/66.7% in landiolol, and 0%/13.8%/17.0%/0% in digoxin (p = 0.003, p < 0.001, p = 0.015 and p = 0.040). This subgroup analysis indicated that landiolol was more useful, regardless of patient characteristics, as compared with digoxin in AF/AFL patients complicated with LV dysfunction. Particularly, in patients with impaired renal function, landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardia.
    Advances in Therapy 03/2014; 31(5). DOI:10.1007/s12325-014-0111-2 · 2.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: General anesthesia is commonly used in the surgical arena, but little is known regarding its influence at the genomic and molecular levels. MicroRNAs (miRNAs) belong to a new class of non-coding RNA molecules which influence cell biology. In the present study, it was hypothesized that miRNAs alter gene expression levels under general anesthesia. The aim was to compare the miRNA expression profiles in the rat hippocampus in response to anesthesia with representative volatile (sevoflurane) and intravenous (propofol) anesthetics. Wistar Rats were randomly assigned to either a 2.4% sevoflurane, 600 µg/kg/min propofol or control (without anesthetics) group. Total RNA from hippocampal samples which contained miRNA was subjected to quantitative reverse transcription-polymerase chain reaction and Taqman Low-Density Arrays (TLDA). A total of 373 miRNAs are associated with rats and the TLDA analysis revealed that 279 expressed miRNAs (74.8%) were expressed in all three groups. Significant differences in the levels of 33 of the 279 expressed miRNAs (11.8%) were observed among the three groups in response to the anesthetic agents, and when compared with the control group, significant differences were found in 26 of the 279 expressed miRNAs (9.3%). Following sevoflurane anesthesia, the levels of four miRNAs were significantly increased and those of 12 were significantly reduced. By contrast, following propofol anesthesia, the levels of 11 miRNAs were significantly reduced but no miRNAs exhibited significantly elevated levels. One miRNA was common between the two anesthesia groups, whereas 14 miRNAs were significantly differentially expressed. In conclusion, sevoflurane and propofol exerted different effects on miRNA expression in the rat hippocampus.
    Molecular Medicine Reports 03/2014; 9(5). DOI:10.3892/mmr.2014.2038 · 1.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously reported that sevoflurane anesthesia reversibly suppresses the expression of the clock gene, Period2 (Per2), in the mouse suprachiasmatic nucleus (SCN). However, the molecular mechanisms underlying this suppression remain unclear. In this study, we examined the possibility that sevoflurane suppresses Per2 expression via epigenetic modification of the Per2 promoter. Mice were anesthetized with a gas mixture of 2.5% sevoflurane/40% oxygen at a 6 L/min flow for 1 or 4 h. After termination, brains were removed and samples of SCN tissue were derived from frozen brain sections. Chromatin immunoprecipitation (ChIP) assays using anti-acetylated-histone antibodies were performed to investigate the effects of sevoflurane on histone acetylation of the Per2 promoter. Interaction between the E'-box (a cis-element in the Per2 promoter) and CLOCK (the Clock gene product) was also assessed by a ChIP assay using an anti-CLOCK antibody. The SCN concentration of nicotinamide adenine dinucleotide (NAD(+)), a CLOCK regulator, was assessed by liquid chromatography-mass spectrometry. Acetylation of histone H4 in the proximal region of the Per2 promoter was significantly reduced by sevoflurane. This change in the epigenetic profile of the Per2 gene was observed prior to suppression of Per2 expression. Simultaneously, a reduction in the CLOCK-E'-box interaction in the Per2 promoter was observed. Sevoflurane treatment did not affect the concentration of NAD(+) in the SCN. Independent of NAD(+) concentration in the SCN, sevoflurane decreases CLOCK binding to the Per2 promoter E'-box motif, reducing histone acetylation and leading to suppression of Per2 expression.
    PLoS ONE 01/2014; 9(1):e87319. DOI:10.1371/journal.pone.0087319 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The two most common forms of chronic pain are inflammatory pain and neuropathic pain. Nevertheless, the underlying mechanisms of these pain conditions and their therapeutic responses are poorly understood. MicroRNAs (miRNAs) negatively regulate cell genes, and thus control cell proliferation, inflammation and metabolism. In the present study, we examined gene expression in the hippocampus of rats in two models of chronic pain. In addition, we used the left hindpaw procedure to identify differences in the bilateral hippocampus. We divided the rats into the 4 following groups: the group with chronic constriction injury (CCI), the sham-operated group, the group injected with complete Freund's adjuvant (CFA) and the group injected with normal saline. miRNA expression profiles were analyzed using TaqMan low-density array (TLDA). We observed 54 miRNAs (22.7%) in the rats with CCI rats that were differentially expressed, including 7 miRNAs that were downregulated compared with the sham-operated rats. In the CFA-injected rats, 40 miRNAs (16.8%) were differentially expressed, including 8 miRNAs that were downregulated compared with the normal saline-injected rats. Pearson's correlation co-efficient for all detected miRNAs in the rat hippocampus failed to identify differences between the hippocampi bilaterally. An unsupervised cluster analysis produced separate clusters between the control and experimental groups. In this study, we demonstrate the differential expression of hippocampal miRNAs in two rat models of chronic pain; however, no significant differences were observed bilaterally in hippocampal miRNA expression. Further research is required to determine the correlation among miRNAs, messenger RNAs (mRNAs) and proteins.
    International Journal of Molecular Medicine 09/2013; 32(6). DOI:10.3892/ijmm.2013.1504 · 1.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, hemoglobin vesicle (HbV), a type of artificial oxygen carrier, was infused in a hemorrhagic shock model, and the findings were compared with those of red blood cell (RBC) transfusion to evaluate the effects on blood pressure and renal function. In rats maintained in hemorrhagic shock for 30 min under general anesthesia, either irradiated stored RBCs from the same strain or HbVs were used for resuscitation. Blood pressure, serum creatinine concentration, and creatinine clearance 24 h after shock were measured. At 2 and 24 h after shock, the kidneys were removed, and the heme oxygenase-1 (HO-1) mRNA level was measured. A histopathology study was performed 24 h after shock. In both the RBC and HbV group, blood pressure recovered significantly immediately after fluid resuscitation, and blood pressure 24 h after shock did not differ significantly between the two groups. Serum creatinine concentration and creatinine clearance 24 h after shock did not differ significantly between the two groups. After 24 h, there was no significant difference in HO-1 mRNA between the groups. In the renal histopathology samples taken at 24 h after shock, there were no obvious differences between the two groups. In conclusion, HbV transfusion improved blood pressure in a manner equivalent to RBC transfusion when administered during hemorrhagic shock, and no renal dysfunction was apparent after 24 h.
    Journal of Artificial Organs 05/2013; DOI:10.1007/s10047-013-0712-6 · 1.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Our previous studies revealed that application of the inhalation anesthetic, sevoflurane, reversibly repressed the expression of Per2 in the mouse suprachiasmatic nucleus (SCN). We aimed to examine whether sevoflurane directly affects the SCN. We performed in vivo and in vitro experiments to investigate rat Per2 expression under sevoflurane-treatment. The in vivo effects of sevoflurane on rPer2 expression were examined by quantitative in situ hybridization with a radioactively-labeled cRNA probe. Additionally, we examined the effect of sevoflurane anesthesia on rest/activity rhythms in the rat. In the in vitro experiments, we applied sevoflurane to SCN explant cultures from Per2-dLuc transgenic rats, and monitored luciferase bioluminescence, representing Per2 promoter activity. Bioluminescence from two peripheral organs, the kidney cortex and the anterior pituitary gland, were also analyzed. Application of sevoflurane in rats significantly suppressed Per2 expression in the SCN compared with untreated animals. We observed no sevoflurane-induced phase-shift in the rest/activity rhythms. In the in vitro experiments, the intermittent application of sevoflurane repressed the increase of Per2-dLuc luminescence and led to a phase delay in the Per2-dLuc luminescence rhythm. Sevoflurane treatment did not suppress bioluminescence in the kidney cortex or the anterior pituitary gland. The suppression of Per2-dLuc luminescence by sevoflurane in in vitro SCN cultures isolated from peripheral inputs and other nuclei suggest a direct action of sevoflurane on the SCN itself. That sevoflurane has no such effect on peripheral organs suggests that this action might be mediated through a neuron-specific cellular mechanism or a regulation of the signal transduction between neurons.
    PLoS ONE 03/2013; 8(3):e59454. DOI:10.1371/journal.pone.0059454 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: A rapid heart rate (HR) during atrial fibrillation (AF) and atrial flutter (AFL) in left ventricular (LV) dysfunction often impairs cardiac performance. The J-Land study was conducted to compare the efficacy and safety of landiolol, an ultra-short-acting β-blocker, with those of digoxin for swift control of tachycardia in AF/AFL in patients with LV dysfunction. Methods and Results: The 200 patients with AF/AFL, HR ≥120beats/min, and LV ejection fraction 25-50% were randomized to receive either landiolol (n=93) or digoxin (n=107). Successful HR control was defined as ≥20% reduction in HR together with HR <110beats/min at 2h after starting intravenous administration of landiolol or digoxin. The dose of landiolol was adjusted in the range of 1-10μg·kg(-1)·min(-1) according to the patient's condition. The mean HR at baseline was 138.2±15.7 and 138.0±15.0beats/min in the landiolol and digoxin groups, respectively. Successful HR control was achieved in 48.0% of patients treated with landiolol and in 13.9% of patients treated with digoxin (P<0.0001). Serious adverse events were reported in 2 and 3 patients in each group, respectively. Conclusions: Landiolol was more effective for controlling rapid HR than digoxin in AF/AFL patients with LV dysfunction, and could be considered as a therapeutic option in this clinical setting.
    Circulation Journal 03/2013; DOI:10.1253/circj.CJ-12-1618 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: We elaborated the rat hippocampi in order to assess for central nervous system changes following a peripheral neuropathic injury. DESIGN, SETTINGSUBJECTS: We examined the gene changes in the hippocampi of chronic constriction injury (CCI) rats with TaqMan® low-density array analysis (TLDA) and quantitative real-time polymerase chain reaction (qRT-PCR) of miR-125b, -132, and messenger RNAs (mRNAs) of neuropeptide Y, brain-derived neural factor, N-methyl-D-aspartate glutamate 2A receptor, gamma-aminobutyric acid A a1 receptor, gamma-aminobutyric acid A b1 receptor, gamma-aminobutyric acid B b2 receptor, serotonin 1A receptor, serotonin 2A receptor, serotonin 2C receptor, and serotonin 3A receptor on days 0, 7, and 15 after surgery. INTERVENTIONS: None. OUTCOME MEASURES: Two behavioral tests (thermal and mechanical stimulation tests) were performed three times at 5-minute intervals to assess pain thresholds. MicroRNA (miRNA) changes were examined by TLDA. mRNA changes were examined by qRT-PCR. Statistical significance was determined by Tukey-Kramer's method and paired t-test. RESULTS: All rats showed mechanical and thermal hypersensitivity on the ipsilateral side. Out of 373 miRNAs analyzed, 237 were expressed, and 51 changed their expressions after CCI. By TLDA, cluster analysis found obvious miRNA changes on day 7 that tended to recover by day 15. For miR-125b, the relative expression decreased to 0.70 ± 0.30 at day 7 and recovered to 1.65 ± 0.19 at day 15. The miR-132 relative expressions were 0.69 ± 0.30 and 0.70 ± 0.15, respectively. The mRNA changes followed the miRNA changes. CONCLUSIONS: Our results showed that the peripheral nerve injury altered rat hippocampal miRNA.
    Pain Medicine 03/2013; 14(5). DOI:10.1111/pme.12066 · 2.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Landiolol hydrochloride is a new β-adrenergic blocker with a pharmacological profile that suggests it can be administered safely to patients who have sinus tachycardia or tachyarrhythmia and who require heart rate reduction. This study aimed to investigate whether intraoperative administration of landiolol could reduce the incidence of atrial fibrillation (AF) after cardiac surgery. Methods Of the 200 consecutive patients whose records could be retrieved between October 2006 and September 2007, we retrospectively reviewed a total of 105 patients who met the inclusion criteria: no previous permanent/persistent AF, no permanent pacemaker, no renal insufficiency requiring dialysis, and no reactive airway disease, etc. Landiolol infusion was started after surgery had commenced, at an infusion rate of 1 μg/kg/min, titrated upward in 3–5 μg/kg/min increments. The patients were divided into 2 groups: those who received intraoperative β-blocker therapy with landiolol (landiolol group) and those who did not receive any β-blockers during surgery (control group). An unpaired t test and Fisher’s exact test were used to compare between-group differences in mean values and categorical data, respectively. Results Seventeen of the 105 patients (16.2%) developed postoperative atrial fibrillation: 5/57 (8.8%) in the landiolol group and 12/48 (25%) in the control group. There was a significant difference between the two groups (P=0.03). The incidence of AF after valve surgery and off-pump coronary artery bypass grafting was lower in the landiolol group, although the difference between the groups was not statistically significant. Conclusions Our retrospective review demonstrated a marked reduction of postoperative AF in those who received landiolol intraoperatively. A prospective study of intraoperative landiolol for preventing postoperative atrial fibrillation is warranted.
    Journal of Cardiothoracic Surgery 01/2013; 8(1):19. DOI:10.1186/1749-8090-8-19 · 3.05 Impact Factor
  • Open Journal of Anesthesiology 01/2013; 03(09):396-401. DOI:10.4236/ojanes.2013.39084
  • Shinji Sugita, Tadashi Okabe, Atsuhiro Sakamoto
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Dexmedetomidine has shown beneficial effects in several inflammatory models, including ischemia-reperfusion injury (IRI). This study investigated whether the continuous infusion of dexmedetomidine could improve renal IRI in rats. Methods: Rats were subjected to either a sham operation and given pentobarbital (10 mg/kg/h; n=6) or were subjected to 45 minutes of renal ischemia and anesthetized with pentobarbital (10 mg/kg/h; n=6), dexmedetomidine (10 or 20 μg/kg/h; both n=6), or both pentobarbital (10 mg/kg/h) and dexmedetomidine (1.0 μg/kg/h; n=6) for 6 hours of reperfusion. Blood urea nitrogen and serum creatinine were measured 6 hours after reperfusion. Gene expression mediated by inflammatory systems in the kidney was measured with the real-time reverse-transcriptase polymerase chain reaction. Results: Treatment with 10 or 20 μg/kg/h of dexmedetomidine reduced renal dysfunction. The increases in the messenger RNA expression of interleukin-6, intercellular adhesion molecule 1, and inducible nitric oxide synthase caused by renal IRI were suppressed. Under In rats under pentobarbital anesthesia, 1.0 μg/kg/h of dexmedetomidine also improved renal dysfunction after renal IRI. Conclusion: The present study demonstrates that continuous infusion of dexmedetomidine improves renal IRI. Moreover, with pentobarbital anesthesia, a dose of dexmedetomidine lower than the sedative dose also improves renal IRI.
    Journal of Nippon Medical School 01/2013; 80(2):131-9. DOI:10.1272/jnms.80.131 · 0.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Preoperative ingestion of only clear fluids until 2 hours before induction of anesthesia is a common preoperative fasting regimen. Gastric emptying times, however, vary among clear fluids. We therefore investigated the gastric emptying of 2 clear glucose-electrolyte drinks. Method: A 2-way crossover study was performed in 10 healthy volunteers. After fasting, the volunteers drank 500 mL of either OS-1(®), an oral rehydration solution, or Pocari Sweat(®), a popular sports drink, over 3 minutes in a standing position. Magnetic resonance imaging was performed before, immediately after, and 30 minutes after the drinking of each test fluid. The difference in gastric emptying between OS-1(®) and Pocari Sweat(®) was evaluated by comparing gastric fluid volume, flow rate, and residual ratio. We also compared the flow rates of sodium, potassium, carbohydrates, and osmotically active particles in the 2 test fluids. Results: Gastric fluid volume 30 minutes after drinking was significantly smaller for OS-1(®) (76.0 ± 57.0 mL) than for Pocari Sweat(®) (158.1 ± 73.5 mL, p<0.01), although the volumes did not differ before or immediately after drinking. The flow rate was significantly faster for OS-1(®) (10.66 ± 3.34 mL) than for Pocari Sweat(®) (8.68 ± 3.02 mL/min, p<0.05), and the residual ratio was significantly smaller for OS-1(®) (21 ± 14% than for Pocari Sweat(®) (41 ± 19%, p<0.01). The flow rates of sodium, potassium, and glucose differed significantly between OS-1(®) and Pocari Sweat(®), whereas the flow rate of osmotically active particles did not. Conclusions: Gastric emptying is significantly faster for OS-1(®) than for Pocari Sweat(®).
    Journal of Nippon Medical School 01/2013; 80(5):342-9. DOI:10.1272/jnms.80.342 · 0.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The present study was conducted to evaluate the efficacy and safety of BLM-240 (desflurane) in comparison to sevoflurane in Japanese patients. A total of 216 patients were enrolled in this randomized comparative study at 15 medical institutions. The patients received either BLM-240 with 50-70 % N(2)O in O(2) (n = 111), BLM-240 with 30 % O(2) in air (n = 55), or sevoflurane with 50-70 % N(2)O in O(2) (n = 50). Efficacy was evaluated by an efficacy rate based on an efficacy evaluation criteria and recovery time to extubation from the discontinuation of the anesthetics. Safety was evaluated by incidence of adverse drug reactions (ADR) and other clinical indicators. The efficacy rate of BLM-240 was 98.8 % (164/166 patients), indicating that BLM-240 is effective as an anesthetic. Time from discontinuation of anesthetic delivery to extubation was 9.7 ± 0.6 min in the BLM-240/N(2)O group and 14.3 ± 0.9 min in the sevoflurane/N(2)O group, meeting the pre-defined non-inferiority criteria of BLM-240 to sevoflurane. There was no statistically significant difference in the incidence of total ADR between the BLM-240 group (62.0 %) and sevoflurane group (48.0 %). The results indicate that BLM-240 is an effective and safe inhalation anesthetic in Japanese patients.
    Journal of Anesthesia 12/2012; 27(3). DOI:10.1007/s00540-012-1536-x · 1.12 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Elucidation of the mechanisms underlying neuropathic pain is expected to aid in the discovery and selection of effective therapeutic methods. Currently, microRNA (miRNA) is thought to play an important role in the development and maintenance of the nervous system. We, therefore, hypothesized that miRNAs are involved in neuropathic pain, and investigated this possibility by analyzing miRNA expression in the dorsal horn of the spinal cord in a chronic constriction injury (CCI) rat model using the TaqMan® Low Density Array (TLDA). Neuropathic pain model rats were produced by CCI induced by ligation of the sciatic nerve. The miRNA expression in the dorsal horn of the spinal cord was analyzed in Day 0 rats, with no sciatic nerve ligation or sham operation, Day 7 rats, examined 7 days after sciatic nerve ligation or sham operation, and Day 14 rats, examined 14 days after sciatic nerve ligation or sham operation using TLDA. In this study, 111 miRNAs were significantly regulated in CCI rats in both the Day 7 and Day 14 groups compared with sham rats in both groups. Of these 111, there were 75 miRNAs (67.6%) that had been analyzed in previous reports and 36 miRNAs (32.4%) related to the development of tumors of the nervous system and neurodegenerative diseases. Certain miRNAs were reported to be related to neuropathic pain; miR-500, -221 and -21. The expression levels of a large number of miRNAs in the dorsal horn of the spinal cord in CCI rats changed. These results provide a step toward elucidation of the mechanisms underlying neuropathic pain.
    International Journal of Molecular Medicine 10/2012; 31(1). DOI:10.3892/ijmm.2012.1163 · 1.88 Impact Factor

Publication Stats

1k Citations
240.30 Total Impact Points

Institutions

  • 1993–2015
    • Nippon Medical School
      • • Department of Anesthesiology
      • • Nippon Medical School Hospital
      • • Department of Surgery
      Edo, Tōkyō, Japan
  • 2007–2012
    • Keio University
      • • Department of Anesthesiology
      • • Department of Surgery
      Tokyo, Tokyo-to, Japan
  • 1991
    • Treatment Research Institute, Philadelphia PA
      Philadelphia, Pennsylvania, United States