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Although the physiological function of receptor-interacting protein kinase (RIPK) 3 has emerged as a critical mediator of programmed necrosis/necroptosis, the intracellular role it plays as an attenuator in human lungs and human bronchial epithelia remains unclear. Here, we show that the expression of RIPK3 dramatically decreased in the inflamed tissues of human lungs, and moved from the nucleus to the cytoplasm. The overexpression of RIPK3 dramatically increased F-actin formation and decreased the expression of genes for pro-inflammatory cytokines (IL-6 and IL-1ß), but not siRNA-RIPK3. Interestingly, whereas RIPK3 was bound to histone 1b without LPS stimulation, the interaction between them was disrupted after 15 min of LPS treatment. Histone methylation could not maintain the binding of RIPK3 and activated movement towards the cytoplasm. In the cytoplasm, overexpressed RIPK3 continuously attenuated pro-inflammatory cytokine gene expression by inhibiting NF-κB activation, preventing the progression of inflammation during Pseudomonas aeruginosa infection. Our data indicated that RIPK3 is critical for the regulation of the LPS-induced inflammatory microenvironment. Therefore, we suggest that RIPK3 is a potential therapeutic candidate for bacterial infection-induced pulmonary inflammation.
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Lipopolisacáridos , Pseudomonas aeruginosa , Humanos , Histonas , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Necrosis , Inflamación/metabolismo , Citocinas/metabolismoRESUMEN
Although diesel airborne particulate matter (PM2.5) has been known to play a role in many human diseases, there is no direct evidence that therapeutic drugs or proteins can diminish PM2.5-induced diseases. Nevertheless, studies examining the negative control mechanisms of PM2.5-induced diseases are critical to develop novel therapeutic medications. In this study, the consensus PDZ peptide of ZO-1 inhibited PM2.5-induced inflammatory cell infiltration, pro-inflammatory cytokine gene expression, and TEER in bronchoalveolar lavage (BAL) fluid and AM cells. Our data indicated that the PDZ domain in ZO-1 is critical for regulation of the PM2.5-induced inflammatory microenvironment. Therefore, the PDZ peptide may be a potential therapeutic candidate during PM-induced respiratory diseases.
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Regulación hacia Abajo , Gasolina/efectos adversos , Material Particulado/efectos adversos , Péptidos/farmacología , Neumonía/inducido químicamente , Neumonía/patología , Proteína de la Zonula Occludens-1/química , Secuencias de Aminoácidos , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Humanos , Dominios PDZ , Tamaño de la PartículaRESUMEN
BACKGROUND: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S') in patients undergoing cardiac surgery. METHODS: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S' at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 µg/min/kg) by using transesophageal echocardiography. RESULTS: Mean S' values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8-12.2), 9.5 (8.3-10.8), and 8.4 (7.3-9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were -1.0 (-1.6, -0.3), -1.1 (-1.7, -0.6), and -2.1 (-3.1, -1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 µg/kg/min at T1, T2, and T3, respectively, P < 0.001). CONCLUSION: Isoflurane increments (1.0-2.0 MAC) dose-dependently reduced LV systolic long-axis performance during cardiac surgeries with a preserved preoperative systolic function.
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Anestésicos por Inhalación/administración & dosificación , Enfermedades de las Válvulas Cardíacas/cirugía , Isoflurano/administración & dosificación , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Anestésicos por Inhalación/farmacología , Ecocardiografía Doppler , Femenino , Humanos , Isoflurano/farmacología , Masculino , Persona de Mediana Edad , Fenilefrina/administración & dosificación , Cuidados Preoperatorios , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
PURPOSE: Surgery during pregnancy can be a cause of preterm labor or birth, possibly resulting from anesthetic agents or direct effects of surgery. This study was aimed to investigate the effect of propofol on uterine contractility by examining prostaglandin E2 (PGE2) production and the expression of PGE synthase 2 (PGES2) and cyclooxygenase-2 (COX-2) in amniotic membrane cells. METHODS: Amniotic membranes were collected from healthy full-term women who underwent cesarean section at 37-40 weeks of gestation. The amniotic cells were cultured in α-modified-Eagle's medium with 10% fetal bovine serum for 24 h at 5% CO2 in a 37 °C incubator. Then, various doses of propofol (0.01-10 µg/ml) were used for treatment for 3 h. PGE2 concentrations in conditioned media were evaluated using ELISA. PGES2 and COX-2 expression were examined using RT-PCR and Western blot. Cell viability and apoptosis were examined by MTT, ATP assays, and the TUNEL method. RESULTS: PGE2 production significantly decreased at 0.1 and 1.0 µg/ml propofol concentrations compared to controls. COX-2 and PGES2 mRNA expression was decreased in a dose-dependent manner with a significant difference at 0.1 µg/ml propofol compared to controls. The protein expression of COX-2 showed a similar result to mRNA expression, but protein expression of PGES2 was not significantly decreased. No effect of propofol was found in cell viability. CONCLUSIONS: This study showed that propofol reduced the production of PGE2 and the expression of COX-2 and PGES2 without affecting cell viability.
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Ciclooxigenasa 2/genética , Dinoprostona/biosíntesis , Propofol/farmacología , Prostaglandina-Endoperóxido Sintasas/genética , Amnios/citología , Amnios/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/farmacología , Femenino , Humanos , EmbarazoRESUMEN
An intraoperative echocardiographic evaluation to determine the feasibility and adequacy of the valve repair procedure is crucial for a successful repair. However, aortic valve repair in severe aortic stenosis (AS) is very limited and, consequently, its intraoperative echocardiographic evaluation has not been described well. Here, we describe an intraoperative transesophageal echocardiographic evaluation of a double-valve repair procedure for a patient with severe AS, moderate aortic insufficiency, and severe mitral stenosis.
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Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Ecocardiografía Transesofágica/métodos , Estenosis de la Válvula Mitral/diagnóstico por imagen , Estenosis de la Válvula Mitral/cirugía , Monitoreo Intraoperatorio/métodos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/complicaciones , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Estenosis de la Válvula Mitral/complicaciones , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
An anatomical understanding of median nerve variation is essential for successful decompression of carpal tunnel syndrome (CTS). Although iatrogenic injury of the thenar branch after carpal tunnel release (CTR) has not been reported in many cases, it can cause serious damage to the patient. In case of rapidly progressing thenar atrophy after CTS surgery, thenar branch of median nerve injury should be suspected. Nerve conduction examination and ultrasound before surgery can be a useful tool for diagnosis.
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While sevoflurane and desflurane have been regarded as inhalation agents providing rapid induction and emergence, previous studies demonstrated the superiority of desflurane-anesthesia compared to sevoflurane-anesthesia in the postoperative recovery in obese and geriatric patients. We investigated whether a short-term switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia enhances patient postoperative recovery profile in non-obese patients. We randomly divide patients undergoing elective surgery (n = 60) into two groups: sevoflurane-anesthesia group (Group-S, n = 30) and sevoflurane-desflurane group (Group-SD, n = 30). In Group-S, patients received only sevoflurane-anesthesia until the end of surgery (for >2 hours). In Group-SD, sevoflurane was stopped and switched to desflurane-anesthesia before the completion of sevoflurane-anesthesia (for approximately 30 minutes). We assessed the intergroup differences in the times to get eye-opening, extubation, and a bispectral index of 80 (BIS-80). Group-SD showed significantly shorter times to get eye-opening (438 ± 101 vs. 295 ± 45 s; mean difference, 143 s; 95% confidence interval [CI], 101-183; p < 0.001), extubation (476 ± 108 vs. 312 ± 42 s; mean difference, 164 s; 95% CI, 116-220; p < 0.001), and BIS-80 (378 ± 124 vs. 265 ± 49 minutes; mean difference, 113 s; 95% CI, 58-168 p < 0.001) compared to Group-S. There was no between-group difference in postoperative nausea, vomiting, and hypoxia incidences. Our results suggested that the short-term (approximately 30 minutes) switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia can facilitate the speed of postoperative patient recovery.
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Anestésicos por Inhalación , Isoflurano , Éteres Metílicos , Anciano , Periodo de Recuperación de la Anestesia , Anestesia General , Anestésicos por Inhalación/farmacología , Desflurano , Humanos , Isoflurano/farmacología , Náusea y Vómito Posoperatorios , SevofluranoRESUMEN
BACKGROUND: This study assessed the effect of a single bolus administration of lidocaine on the prevention of tourniquet-induced hypertension (TIH) and compared the effect of lidocaine to that of ketamine in patients undergoing general anesthesia. METHODS: This randomized, controlled, double-blind study included 75 patients who underwent lower limb surgery using a tourniquet. The patients were administered lidocaine (1.5 mg/kg, n = 25), ketamine (0.2 mg/kg, n = 25) or placebo (n = 25). The study drugs were administered intravenously 10 min before tourniquet inflation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured before tourniquet inflation, after tourniquet inflation for 60 min at 10 min intervals, and immediately after tourniquet deflation. The incidence of TIH, defined as an increase of 30% or more in SBP or DBP during tourniquet inflation, was also recorded. RESULTS: SBP, DBP, and HR increased significantly over time in the control group compared to those in the lidocaine and ketamine groups for 60 min after tourniquet inflation (P < 0.001, P < 0.001, and P = 0.007, respectively). The incidence of TIH was significantly lower in the lidocaine (n = 4, 16%) and ketamine (n = 3, 12%) group than in the control group (n = 14, 56%) (P = 0.001). CONCLUSION: Single-bolus lidocaine effectively attenuated blood pressure increase due to tourniquet inflation, with an effect comparable to that of bolus ketamine.
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In the case of a cat bite patient, even if the external wound is small, prophylactic antibiotics should be used early and a closed observation is needed. If symptoms persist, deep infection should be considered.
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Objective To determine whether pre-treatment with high-dose ulinastatin provides enhanced postoperative oxygenation in patients who have undergone aortic valve surgery with moderate hypothermic cardiopulmonary bypass (CPB). Methods Patients who underwent aortic valve surgery with moderate hypothermic CPB were retrospectively evaluated. In total, 94 of 146 patients were included. The patients were classified into one of two groups: patients in whom ulinastatin (10,000 U/kg followed by 5,000 U/kg/h) was administered during CPB (Group U, n = 38) and patients in whom ulinastatin was not administered (Group C, n = 56). The PaO2/FiO2 ratio was calculated at the following time points: before CPB (pre-CPB), 2 h after weaning from CPB (post-CPB), and 6 h after arrival to the intensive care unit (ICU-6). The incidence of a low PaO2/FiO2 ratio was also compared among the time points. Results Group U showed a significantly higher PaO2/FiO2 ratio (F(4, 89.0) = 657.339) and a lower incidence of lung injury (PaO2/FiO2 ratio < 300) than Group C at the post-CPB and ICU-6 time points. Conclusion High-dose ulinastatin improved pulmonary oxygenation after CPB and in the early stages of the ICU stay in patients undergoing aortic valve surgery with CPB.
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Lesión Pulmonar Aguda/prevención & control , Insuficiencia de la Válvula Aórtica/cirugía , Puente Cardiopulmonar , Glicoproteínas/uso terapéutico , Complicaciones Posoperatorias/diagnóstico , Inhibidores de Tripsina/uso terapéutico , Lesión Pulmonar Aguda/etiología , Adulto , Anciano , Válvula Aórtica/patología , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/patología , Femenino , Humanos , Hipotermia Inducida/efectos adversos , Unidades de Cuidados Intensivos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/patología , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway. [BMB Reports 2017; 50(10): 516-521].
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Bronquios/efectos de los fármacos , Claudina-1/biosíntesis , Mucina 5AC/biosíntesis , Material Particulado/toxicidad , Bronquios/citología , Bronquios/metabolismo , Línea Celular , Claudina-1/genética , Claudina-1/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Inflamación/metabolismo , Interleucina-6/metabolismo , Mucina 5AC/genética , Mucina-1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Coughing during emergence from general anesthesia may be detrimental. Propofol is known to inhibit airway reflexes. We evaluated the incidence and severity of coughing in adults who received a subhypnotic dose of propofol at the end of sevoflurane-remifentanil anesthesia. METHODS: Sixty patients, aged 18-65 years, undergoing elective nasal surgery under general anesthesia using sevoflurane and remifentanil were randomly allocated to the propofol group (n = 30) or the control group (n = 30). At the end of surgery, sevoflurane and remifentanil infusion was stopped. After 3 min, the propofol group received propofol 0.3 mg/kg and the control group received normal saline 0.03 ml/kg. The incidence and severity of cough, recovery time and hemodynamic parameters were evaluated during the emergence period. RESULTS: During emergence, the propofol group had the significantly lower incidence (60 vs. 87%) and severity of coughing compared with the control group (P = 0.04, P = 0.02, respectively). There were no significant differences in mean arterial pressure, heart rate, and recovery time during emergence between the two groups. CONCLUSIONS: During emergence from sevoflurane-remifentanil anesthesia, a subhypnotic dose (0.3 mg/kg) of propofol decreases the incidence and severity of coughing without delaying wake up in adults undergoing nasal surgery.
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BACKGROUND: G protein-coupled receptor, family C, group 5 (GPRC5B), a retinoic acid-inducible orphan G-protein-coupled receptor (GPCR), is a member of the group C metabotropic glutamate receptor family proteins presumably related in non-canonical Wnt signaling. In this study, we investigated altered GPRC5B expression in the dorsal horn of the spinal cord after spinal nerve injury and its involvement in the development of neuropathic pain. METHODS: After induction of anesthesia by intraperitoneal injection of pentobarbital (35 mg /kg), the left L5 spinal nerve at the level of 2 mm distal to the L5 DRG was tightly ligated with silk and cut just distal to the ligature. Seven days after nerve injury, animals were perfused with 4% paraformaldehyde, and the spinal cords were extracted and post-fixed at 4â overnight. To identify the expression of GPRC5B and analyze the involvement of GPRC5B in neuropathic pain, immunofluorescence was performed using several markers for neurons and glial cells in spinal cord tissue. RESULTS: After L5 spinal nerve ligation (SNL), the expression of GPRC5B was decreased in the ipsilateral part, as compared to the contralateral part, of the spinal dorsal horn. SNL induced the downregulation of GPRC5B in NeuN-positive neurons in the spinal dorsal horn. However, CNPase-positive oligodendrocytes, OX42-positive microglia, and GFAP-positive astrocytes were not immunolabeled with GPRC5B antibody in the spinal dorsal horn. CONCLUSIONS: These results imply that L5 SNL-induced GPRC5B downregulation may affect microglial activation in the spinal dorsal horn and be involved in neuropathic pain.
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An 81-year-old male patient was scheduled for a laparoscopic cholecystectomy due to acute cholecystitis. About 50 minutes into the operation, the arterial blood pressure suddenly decreased and ventricular fibrillation appeared on the electrocardiography. The patient received cardiopulmonary resuscitation and recovered a normal vital sign. We suspected a carbon dioxide embolism as the middle hepatic vein had been injured during the surgery. We performed a transesophageal echocardiography and were able to confirm the presence of multiple gas bubbles in all of the cardiac chambers. After the operation, the patient presented a stable hemodynamic state, but showed weaknesses in the left arm and leg. There were no acute lesions except for a chronic cerebral cortical atrophy and chronic microvascular encephalopathy on the postoperative brain-computed tomography, 3D angiography and magnetic resonance image. Fortunately, three days after the operation, the patient's hemiparesis had entirely subsided and he was discharged without any neurologic sequelae.
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BACKGROUND: Unlike the right internal jugular vein (RIJV), there is a paucity of data regarding the effect of the Trendelenburg position on the left internal jugular vein (LIJV). The purpose of this study is to investigate the cross-sectional area (CSA) of the LIJV and RIJV and their response to the Trendelenburg position using two-dimensional ultrasound in adult subjects. METHODS: This study enrolled fifty-eight patients with American Society of Anesthesiologists physical status class I-II who were undergoing general anesthesia. CSAs of both the RIJV and LIJV were measured with a two-dimensional ultrasound in the supine position and then in a 10° Trendelenburg position. RESULTS: In the supine position, the transverse diameter, anteroposterior diameter, and CSA of the RIJV were significantly larger than those of the LIJV (P < 0.001). Of 58 patients, the RIJV CSA was larger than the LIJV CSA in 43 patients (74.1%), and the LIJV CSA was larger than the RIJV CSA in 15 patients (25.9%). In the Trendelenburg position, CSAs of the RIJV and LIJV increased 39.4 and 25.5%, respectively, compared with the supine position. However, RIJV changed at a rate that was significantly greater than that of the LIJV (P < 0.05). Of 58 patients, the RIJV CSA was larger than the LIJV CSA in 48 patients (82.8%), and the LIJV CSA was larger than the RIJV CSA in 10 patients (17.2%). CONCLUSIONS: In supine position, the RIJV CSA was larger than the LIJV CSA. The increased CSA in the Trendelenburg position was greater in the RIJV than the LIJV.
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MicroRNA (miRNA) pathways have been implicated in stem cell regulation. This study investigated the molecular effects of propofol on adipocyte stem cells (ASCs) by analyzing RNA expression arrays. Human ASCs were isolated by use of a liposuction procedure. ASCs were treated with saline, 50 µM propofol, or 100 µM propofol in culture media for 3 hours. After the isolation of total RNA, the expression of 76 miRNAs was evaluated with peptide nucleic acid-miRNA array analysis through denaturation and hybridization processes. Treatment with 50 µM propofol resulted in significant down-regulation of expression of 18 miRNAs and upregulation of expression of 25 miRNAs; 100 µM propofol resulted in significant downregulation of expression of 14 miRNAs and upregulation of expression of 29 miRNAs. The lowest expression was seen for miR-204, which was 0.07-fold with 50 µM propofol and 0.18-fold with 100 µM propofol. The highest expression was seen for miR-208b, which was 11.23-fold with 50 µM propofol and 11.20-fold with 100 µM propofol. Expression patterns of miRNAs were not significantly different between 50 µM and 100 µM propofol treatment. The results of this study suggest that propofol is involved in altering the miRNA expression level in human ASCs. Additional research is necessary to establish the functional effect of miRNA alteration by propofol.
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Cortriatriatum is a rare congenital cardiac disorder with fibromuscular band (diaphragm) dividing the left atrium (LA) into the proximal and distal parts. Surgical correction of cortriatriatum requires full preoperative evaluation of the structural anomalies including the LA diaphragm and their pathophysiology. In the present case, a 44 year-old lady diagnosed as cortriatriatum underwent surgical correction. Intraoperative three-dimensional transesophageal echocardiography provided detailed information regarding the shape and extent of the LA diaphragm, which had been partially evaluated by preoperative two-dimensional transthoracic and transesophageal echocardiography, and facilitated the intraoperative patient management and surgical decision making.
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BACKGROUND: The effects of dexmedetomidine on the propofol-sparing effect and intraoperative hemodynamics during remifentanil-based propofol-supplemented anesthesia have not been well investigated. METHODS: Twenty patients undergoing breast surgery were randomly allocated to receive dexmedetomidine (group DEX) or placebo (group C). In the DEX group, dexmedetomidine was loaded (1 µg/kg) before anesthesia induction and was infused (0.6 µg/kg/h) during surgery. Anesthesia was induced with a target-controlled infusion (TCI) of propofol (effect site concentration, Ce; 3 µg/ml) and remifentanil (plasma concentration, Cp, 10 ng/ml). The Ce of TCI-propofol was adjusted to a bispectral index of 45-55, and Cp of TCI-remifentanil was fixed at 10 ng/ml in both groups. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at baseline (T-control), after the loading of study drugs (T-loading), 3 min after anesthesia induction (T-induction), tracheal intubation (T-trachea), incision (T-incision), 30 min after incision (T-incision30), and at tracheal extubation (T-extubation). MAP% and HR% (MAP and HR vs. T-control) were determined and the propofol infusion rate was calculated. RESULTS: The propofol infusion rate was significantly lower in the DEX group than in group C (63.9 ± 16.2 vs. 96.4 ± 10.0 µg/kg/min, respectively; P < 0.001). The changes in MAP% at T-induction, T-trachea and T-incision in group DEX (-10.0 ± 3.9%, -9.4 ± 4.6% and -11.2 ± 6.3%, respectively) were significantly less than those in group C (-27.6 ± 13.9%, -21.7 ± 17.1%, and -25.1 ± 14.1%; P < 0.05, respectively). CONCLUSIONS: Dexmedetomidine reduced the propofol requirement for remifentanil-based anesthesia while producing more stable intraoperative hemodynamics.