Ju Deok Kim

The effect of dexmedetomidine on the adjuvant propofol requirement and intraoperative hemodynamics during remifentanil-based anesthesia.

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.

G protein-coupled receptor, family C, group 5 (GPRC5B) downregulation in spinal cord neurons is involved in neuropathic pain

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 4℃ 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.

Effect of Propofol on microRNA Expression Profile in Adipocyte-Derived Adult Stem Cells.

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.

IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation

Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca2+ signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells

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.

Effect of Trendelenburg position on right and left internal jugular vein cross-sectional area

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.

Isoflurane's Effect on Intraoperative Systolic Left Ventricular Performance in Cardiac Valve Surgery Patients.

Background Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isofluranes 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.

High-dose ulinastatin improves postoperative oxygenation in patients undergoing aortic valve surgery with cardiopulmonary bypass: A retrospective study:

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.

The effect of a subhypnotic dose of propofol for the prevention of coughing in adults during emergence from anesthesia with sevoflurane and remifentanil

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.

Paradoxical carbon dioxide embolism during laparoscopic cholecystectomy as a cause of cardiac arrest and neurologic sequelae: a case report

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 patients hemiparesis had entirely subsided and he was discharged without any neurologic sequelae.