[Show abstract][Hide abstract] ABSTRACT: The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABAA and GABAB receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm.
No preview · Article · Dec 2015 · Neuroscience Research
[Show abstract][Hide abstract] ABSTRACT: Previous reports have shown that electroconvulsive therapy (ECT) is efficacious in the treatment of neuropathic pain; however, its mechanism of action remains unclear. The present study aimed to understand these mechanisms by investigating the alterations in the expression of neuropeptide Y (NPY) and interleukin-1β (IL-1β) in the prefrontal cortex. A rat model of neuropathic pain produced by chronic constrictive injury of the sciatic nerve was used, and mechanical and thermal hyperalgesia were evaluated starting 2 days after the injury. Using a pulse generator, ECT was administered to the rodents for 6 days from days 7-12 after the injury. Thermal and mechanical stimulation were administered to assess pain thresholds. Quantitative polymerase chain reaction, used to measure gene expression levels in the prefrontal cortex, showed that NPY and IL-1β gene expression levels in the prefrontal cortex increased following the injury. The present results indicate that these gene expression level variations may be associated with the mechanisms underlying the effect of ECT in treating neuropathic pain.
[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.
[Show abstract][Hide abstract] ABSTRACT: Second-line therapy has limited activity in patients with recurrent or persistent uterine cervical cancer that has progressed after chemoradiation and palliative chemotherapy. The purpose of this study was to evaluate the efficacy of negative-balance isolated pelvic perfusion (NIPP) in patients with pretreated recurrent/persistent uterine cervical cancer.
Between April 2004 and May 2013, a total of 26 patients with recurrent or persistent uterine cervical cancer previously treated with platinum-based systemic chemotherapy and/or chemoradiotherapy received NIPP therapy at our institution, consisting of a 30-min isolated pelvic perfusion with cisplatin and fluorouracil, followed by isolated pelvic dialysis. Primary endpoints were response rate (RR) and progression-free survival (PFS), while secondary endpoints were overall survival (OS) and safety. Platinum pharmacokinetics were also evaluated.
The RR was 57.7 % (complete response, five patients; partial response, ten patients). The median PFS and OS after NIPP therapy were 11.0 (95 % confidence interval [CI] 6.6-15.4) and 25.1 (95 % CI 17.1-33.1) months, respectively. PFS was significantly better in patients without intestinal involvement (p = 0.016) or dissemination (p < 0.001). Survival rates at 1, 2, and 3 years after initial NIPP therapy were 65.2, 50.4, and 13.4 %, respectively. The plasma pelvic-to-systemic exposure ratios were 15.4 and 15.8, based on the maximum concentration and the concentration-time curve, respectively. Most adverse events were mild (grade 1-2) (Common Terminology Criteria for Adverse Events, version 3.0). Severe neutropenia (grade 3 or higher) occurred in only 7.7 % of patients.
NIPP appears to be an effective and feasible method for patients with pretreated recurrent or persistent cervical cancer.
No preview · Article · Mar 2015 · Annals of Surgical Oncology
[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.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
The 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.
Rats 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 injected intrathecally to assess the involvement of descending inhibition in GDNF-mediated analgesia. The MEK inhibitor U0126 was used to investigate whether the ERK signalling pathway plays a role in the analgesic effects of GDNF.
Both 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 partly, but significantly, inhibited by prior injection of U0126 into the LC.
Conclusions and implications:
GDNF injection into the LC exerts prolonged analgesic effects on neuropathic pain in rats by enhancing descending noradrenergic inhibition.
No preview · Article · Jan 2015 · British Journal of Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Commonly used anesthetics adversely affect the developing brain, but the mechanisms remain unknown. We previously showed that the expressions of microRNAs (miRNAs) in major organs are affected by anesthetics. Therefore, we used TaqMan low-density array (TLDA) to analyze gene expression in the hippocampus of neonatal rats exposed to sevoflurane and performed behavioral tests after they reached adulthood to evaluate cognitive and memory function. Rat male pups at postnatal day 7 were exposed to 1.9% sevoflurane for 3 h, and the hippocampus-miRNA expression profile on postnatal day 8 was determined. Open field and fear conditioning tests conducted during postnatal weeks 7 and 8 indicated that sevoflurane-exposed rats, but not controls, exhibited anxiety-like disorders. TLDA analysis identified 20 differentially expressed miRNAs, which were not shared between postnatally and maturely sevoflurane-exposed rats. The level of rno-miR-632, which targets brain-derived neurotrophic factor and calcium channel, voltage-dependent, alpha 2/delta subunit 2, increased by 10-fold, indicating that exposure to sevoflurane during early neural development alters hippocampus-miRNA expression and may induce subsequent behavioral disorders.
No preview · Article · Jan 2015 · Biomedical Research
[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.
We enrolled 60 patients who required a transnasal gastric tube to facilitate elective abdominal surgery under general anesthesia. The participants were recruited consecutively into one of two groups, a group of 30 patients in whom a gastric tube was inserted using a King Vision™ video laryngoscope (KV group), and a group of 30 patients who underwent conventional blind insertion of the gastric tube (Blind group). The success rate, the time taken to insert the gastric tube, and the incidence of complications were compared.
In the KV group, the time required for gastric tube placement was 52.5 ± 17.1 seconds, with a success rate of 100%. Slight oral hemorrhage occurred in two participants and slight epistaxis in one participant. In the Blind group, the time required for gastric tube placement was 65.9 ± 39.9 seconds, with a success rate of 90% (27 out of 30 patients). Slight oral hemorrhage occurred in two participants, slight epistaxis occurred in two participants, and tracheal malposition occurred in one participant but was detected promptly and corrected using the video laryngoscope. There were no significant differences in the time required for placing the gastric tube, the success rate, or the incidence of complications between the groups.
Gastric tube insertion using a King Vision video laryngoscope was straightforward, and was particularly useful for detecting and correcting tracheal malpositioning.
Trial registry number:
[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.
No preview · Article · May 2014 · Masui. The Japanese journal of anesthesiology
[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.
Full-text · Article · Apr 2014 · Advances in Therapy
[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.
Full-text · Article · Mar 2014 · Advances in Therapy
[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.
Preview · Article · Mar 2014 · Molecular Medicine Reports
[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.
[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.
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.
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.
Gastric emptying is significantly faster for OS-1(®) than for Pocari Sweat(®).
No preview · Article · Nov 2013 · Journal of Nippon Medical School
[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.
Preview · Article · Sep 2013 · International Journal of Molecular Medicine
[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.
No preview · Article · May 2013 · Journal of Artificial Organs
[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.
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.
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.
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.
No preview · Article · May 2013 · Journal of Nippon Medical School