Lactated Ringer' Solution may be Superior to Saline-Based 6% Hydroxyethyl Starch 130/0.4 for Early Resuscitation within 12 hours from Hemorrhagic Shock.

Purpose: To compare the effects of fluid resuscitation with lactated Ringer's solution (LR) and saline-based 6% hydroxyethyl starch 130/0.4 (HES) on the inflammatory response and oxidative stress in the small intestine as well as on bacterial translocation to the liver. Methods: Sprague-Dawley rats were subjected to blood pressure-controlled hemorrhagic shock and then resuscitated with LR or HES. At 1, 3, 6, 12, and 24 hr after resuscitation, liver tissues were collected to count the bacterial colonies, and small intestines were harvested to analyze the levels of inflammatory (TNF-α and HO-1) and oxidative stress (MPO) mediators as well as the intestinal injury by immunohistochemistry, colorimetry and hematoxylin & eosin staining, respectively. Results: The expression level of TNF-α in the LR group was stable from 1 to 6 hr but decreased at 12 hr and then abruptly increased at 24 hr. The expression level of TNF-α in the LR group was significantly lower than that in the HES group, especially during the first 12 hr post-fluid infusion. MPO activity decreased to its lowest level at 3 hr but increased from 6 to 12 hr, with no difference at 24 hr between the two groups. Although a decreasing tendency was observed from 6 hr, HO-1 expression levels remained higher in the LR group than in the HES group at 12 and 24 hr, particularly at 12 hr. During the initial 12 hr, the LR group exhibited significantly lower colony-forming units in the liver tissues than the HES group. Chiu's score in the intestine decreased regardless of which resuscitative fluids were used. Conclusions: During early resuscitation (within 12 hr), LR may be superior to HES in reducing intestinal injuries by suppressing inflammatory and oxidative mediators.

Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy.

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Establishment and Validation of a Prediction Equation to Estimate Risk of Intraoperative Hypothermia in Patients Receiving General Anesthesia.

Inadvertent intraoperative hypothermia (core temperature <36 °C) is a frequent but preventable complication of general anesthesia. Accurate risk assessment of individual patients may help physicians identify patients at risk for hypothermia and apply preventive approaches, which include active intraoperative warming. This study aimed to develop and validate a risk-prediction model for intraoperative hypothermia. Two independent observational studies in China, the Beijing Regional Survey and the China National Survey, were conducted in 2013 and 2014, respectively, to determine the incidence of hypothermia and its underlying risk factors. In this study, using data from these two studies, we first derived a risk calculation equation, estimating the predictive risk of hypothermia using National Survey data (3132 patients), then validated the equation using the Beijing Regional Survey data (830 patients). Measures of accuracy, discrimination and calibration were calculated in the validation data set. Through validation, this model, named Predictors Score, had sound overall accuracy (Brier Score = 0.211), good discrimination (C-Statistic = 0.759) and excellent calibration (Hosmer-Lemeshow, P = 0.5611). We conclude that the Predictors Score is a valid predictor of the risk of operative hypothermia and can be used in deciding whether intraoperative warming is a cost-effective measure in preventing the hypothermia.

Effects and mechanism of dexmedetomidine on neuronal cell injury induced by hypoxia-ischemia.

BACKGROUND: The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells. METHODS: PC12 cells exposed to OGD was used to establish ischemia model. The OGD-induced cell injury was evaluated by alterations of cell viability, apoptosis and expressions of apoptosis-associated proteins. Oxidative stress and expressions of neurotrophic factors after OGD and DMED treatments were also explored. The activation of possible involved signaling pathways were studied after OGD and DMED treatments, along with the addition of inhibitors of these pathways. Finally, the effects of DMED on primary neuronal cells were verified according to the alterations of inflammatory cytokines release and oxidative stress. RESULTS: DMED obviously increased cell viability and reduced cell apoptosis as well as ratio of Bax/Bcl-2 in OGD-treated PC12 cells. Then, the OGD-induced changes of LDH, MDA, SOD and GSH-Px as well as decreases of neurotrophic factors were all ameliorated by DMED treatment. Key kinases in Notch/NF-κB signaling pathway were up-regulated by OGD, whereas the up-regulations were decreased by DMED. In addition, inhibitor of Notch or NF-κB could augment the effects of DMED on OGD-induced cell injury. Finally, the protective effects of DMED were verified in primary neuronal cells. CONCLUSION: DMED had protective effect on OGD-induced PC12 cell injury, depending on its anti-apoptotic, anti-oxidative activity and the inhibition of Notch/NF-κB activation. Our findings suggested that DMED could be used as a potential therapeutic drug for cerebral ischemia.

Intraoperative hypothermia and its clinical outcomes in patients undergoing general anesthesia: National study in China.

BACKGROUND/OBJECTIVE: Inadvertent intraoperative hypothermia (core temperature <36°C) is a frequently preventable complication with several adverse consequences. Our study aimed to determine the overall incidence of inadvertent intraoperative hypothermia and its risk factors associated with clinical outcomes in this national survey in China. METHODS: We conducted a national cross-sectional study with 30 days postoperative follow-up from November 2014 through August 2015. A total of 3132 eligible patients underwent general anesthesia were randomly selected from 28 hospitals in the nationwide of China. RESULTS: The overall incidence of intraoperative hypothermia was as high as 44.3%, in which cumulative incidence rates of hypothermia being 17.8%, 36.2%, 42.5% and 44.1% within 1 h, 2 h, 3 h and 4 h respectively following induction of anesthesia. All patients were warmed passively by covering of surgical draping, sheets or cotton blankets, whereas only 14.2% of patients received active warming with space heaters or electric heater or electronic blankets. Compared to normothermic patients, patients with hypothermia is associated with more postoperative ICU admit, longer PACU and more postoperative hospital days, but no difference in surgical site infection (SSI) rates or 30-day mortality. Several factors were shown to be associated with decreased risk of hypothermia. They are active warming (OR = 0.46, 95% CI 0.26-0.81), BMI ≥ 25 (OR = 0.54, 95% CI 0.45-0.65), higher baseline core temperature (OR = 0.04, 95% CI 0.03-0.06), and higher ambient temperature (OR = 0.83, 95% CI 0.78-0.88). Risk factors associated with an increased risk of hypothermia included major-plus surgery (OR = 1.49, 95% CI 1.23-1.79), and long anesthesia (>2 h) (OR = 2.60, 95% CI 2.09-3.24). CONCLUSIONS: The incidence of intraoperative hypothermia in China is high, and the rate of active warming of patients during operation is low. Hypothermia is associated with more postoperative shivering, increased ICU admissions, and longer postoperative hospital days.

Nobiletin ameliorates isoflurane-induced cognitive impairment via antioxidant, anti-inflammatory and anti-apoptotic effects in aging rats.

A recent study reported that nobiletin is an active ingredient in Fructus Aurantii immaturus and Pericarpium Citri Reticulatae, which may be capable of preventing ischemic stroke. Therefore, the present study aimed to determine the neuroprotective effects of nobiletin, and to evaluate whether it could ameliorate isoflurane­induced cognitive impairment via antioxidant, anti­inflammatory and anti­apoptotic effects in aging rats. Male Sprague­Dawley rats (age, 18 months) were used to analyze the neuroprotective effects of nobiletin. Morris water maze test was used to determine cognitive competence. Enzyme­linked immunosorbent assay and western blot analysis were also used to quantify nuclear factor­κB, tumor necrosis factor (TNF)­α, IL­1ß, IL­6, glutathione, (GSH), GSH­peroxidase, superoxide dismutase and malondialdehyde concentration and relevant protein expression levels Cognitive competence was increased in isoflurane-treated rats following treatment with nobiletin. In addition, as expected, nobiletin exerted antioxidant, anti-inflammatory and anti­apoptotic effects on isoflurane­induced cognitive impairment in aging rats. Treatment with nobiletin induced the activation of phosphorylated (p)­Akt, p­cAMP response element binding protein (CREB) and brain­derived neurotrophic factor (BDNF) protein expression and reduced the levels of B­cell lymphoma 2­associated X protein (Bax) in isoflurane­induced rats. In conclusion, the present study demonstrated that nobiletin may ameliorate isoflurane-induced cognitive impairment through antioxidant, anti­inflammatory and anti­apoptotic effects via modulation of Akt, Bax, p­CREB and BDNF in aging rats. These findings provide support for the molecular mechanisms underlying the effects of nobiletin treatment on isoflurane-induced damage.

Management of Postoperative Pain in Medical Institutions in Shandong Province in China.

The aim of the study was to investigate current situation of postoperative pain management in medical institutions in Shandong Province.A questionnaire was developed on the basis of guidelines of acute pain and pain quality assessment scale. The questionnaire was used to obtain information regarding the nature and scale of the medical institution, structure of pain management organization, implementation of pain assessment, and analgesic techniques and processes used in clinical practice. A multistage stratified and cluster sampling method was employed to investigate the current situation of postoperative pain management in 168 medical institutions in Shandong Province.For acute pain service (APS), 32% of the hospitals established postoperative pain management organizations similar to APS. For pain evaluation, 57.1% of the hospitals evaluated pain as the fifth vital sign, and 47.0% of the hospitals evaluated pain at rest and during activity. Furthermore, 43.0% of the surveyed hospitals employed patient-controlled analgesia mode, of which hospitals employing brachial plexus block, lumbar plexus block, and femoral nerve block analgesia accounted for 5.0%, 1.0%, and 4.0%, respectively. The survey revealed that 51.0% of the hospitals educated patients about pain and pain management, of which patients were postoperatively educated by ward nurses in 5.0% and patients were educated by APS during ward rounds in 2.0%.There is a lack of standardized postoperative pain management, the involvement of nurses in pain management is scarce, and the pain assessment and education and application of advanced analgesic management techniques were found to be inadequate in medical institutions in Shandong Province.

Undiagnosed giant cystic pheochromocytoma: A case report.

Giant cystic pheochromocytomas (GPCCs) are rare adrenal tumors and the majority of them present as asymptomatic. As a result GPCCs often remain undiagnosed until surgery and therefore the surgical team face a greater challenge in perioperative management. The present study describes the case of a 36 year-old woman with an undiagnosed GPCC, which was successfully resected despite the occurrence of perioperative cardiovascular events, including hypertension, hypotension, ventricular arrhythmias, acute heart failure, acute myocardial infarction, and the patient was discharged home without any recurrence. It should be considered in retroperitoneal tumour of patients with nonspecific symptoms and given adequate treatment to promote the perioperative safety.

Intraoperative intravenous lidocaine exerts a protective effect on cell-mediated immunity in patients undergoing radical hysterectomy.

Surgical procedures cause a decrease in lymphocyte proliferation rate, an increase in apoptosis and shifts the balance of T­helper (Th)1/Th2 cells towards anti­cell­mediated immunity (CMI) Th2 dominance, which is relevant to the immunosuppressive effects of CMI, postoperative septic complications and the formation of tumor metastasis. Previous studies have revealed that lidocaine exhibits antibacterial actions; regulating inflammatory responses, reducing postoperative pain and affecting the duration spent in hospital. Thus, the present study hypothesized that lidocaine may exert a protective effect on the CMI of patients undergoing surgery for the removal of a primary tumor. A total of 30 adult female patients diagnosed with cervical cancer were recruited to the present study and were randomized into two groups. The lidocaine group received an intravenous bolus dose of 1.5 mg/kg lidocaine, followed by continuous infusion at 1.5 mg/kg/h until discharge from the operating room. The control group received the same volume of normal saline. A 10 ml sample of venous blood was drawn, and the lymphocytes were isolated using Ficoll­paque 1 day prior to surgery, at discharge from the operating room and 48 h post­surgery. The proliferation rate of the lymphocytes was assessed using a Cell Counting Kit­8 assay and was found to be higher in the lidocaine group. The early apoptosis of lymphocytes was attenuated following lidocaine treatment at 48 h post­surgery, as detected using flow cytometry with Annexin V­fluorescein isothiocyanate/propidium iodide staining. The level of interferon (IFN)­Î³ in the serum at 48 h was significantly decreased following surgery in the control group, compared with the pre­surgical values (3.782 ± 0.282, vs. 4.089 ± 0.339 pg/ml, respectively) and the ratio of IFN­Î³ to interleukin­4 was well preserved in the lidocaine group. In conclusion, the present study demonstrated that the intraoperative systemic administration of lidocaine exerted a protective effect on CMI in patients with cervical cancer undergoing radical hysterectomy. This may be beneficial in reducing the occurrence of postoperative septic complications and tumor metastasis formation.

The effects of dexmedetomidine on post-operative cognitive dysfunction and inflammatory factors in senile patients.

OBJECTIVE: To evaluate the effect of dexmedetomidine on post-operative cognitive dysfunction (POCD) and possible action mechanisms. METHODS: A total of 148 aged surgical patients were divided into two groups, which were treated with dexmedetomidine (Dex group) or normal saline (control group) during general anesthesia. The incidence of POCD one day after surgery was evaluated using Mini-Mental State Examination and serum levels of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were measured using ELISA. The correlation between the two cytokines and POCD was evaluated using quartile division assay. RESULTS: The incidence of POCD was 9.20% and 21.31% in Dex and control groups, respectively. It is significantly different between the two groups (P < 0.05). The levels of IL-6 and TNF-α were significantly increased after surgery, as compared to before surgery (P < 0.05). Compared to control group, Dexmedetomidine significantly inhibited the increase of post-operative IL-6 and TNF-α levels (P < 0.05). The incidence of POCD was significantly different between quartile divisions of IL-6 and TNF-α (P < 0.05). Pearson correlation analysis showed that IL-6 and TNF-α were positively correlated with the POCD (r = 0.689, P = 0.043 and r = 0.711, P = 0.038, respectively). CONCLUSIONS: The results demonstrate that dexmedetomidine reduces the incidence of POCD in aged patients, and inflammation suppression may underlie the action mechanism.

Doxapram hastens the recovery following total intravenous anesthesia with dexmedetomidine, propofol and remifentanil.

Dexmedetomidine is a suitable sedative for awake fiberoptic intubation in patients with obstructive sleep apnea (OSA). However, previous studies have shown that dexmedetomidine delays recovery from propofol-remifentanil anesthesia. This study aimed to determine whether doxapram may hasten the recovery following dexmedotomidine-propofol-remifentanil anesthesia. Sixty patients scheduled for uvulopalatopharyngoplasty with total intravenous anesthesia were randomized to two groups according to the medicine given at the end of surgery. These were the doxapram (1 mg/kg) and control (normal saline) groups (n=30 per group). The primary outcome was the time to eye opening on verbal command. The time to return to spontaneous breathing, to hand squeezing in response to verbal command, to extubation of the trachea, and the heart rate (HR), bispectral index (BIS) values, respiratory rate (RR) and pulse oximetry values were also recorded and compared. The time to return to spontaneous breathing (5.2±2.9 vs. 11.7±3.4 min, P<0.001), eye opening (9.3±4.7 vs. 15.9±6.3 min, P<0.001), hand squeeze to command (11.8±6.5 vs. 17.6±7.7 min, P=0.0026) and extubation (14.2±7.8 vs. 19.2±9.6 min, P=0.0308) were significantly shorter in the doxapram group compared with the control group. BIS scores (at 3-14 min), RR (at 4-10 min) and HR (at 2-13 min) were significantly higher in the doxapram group compared with those in the control group (P<0.05). Doxapram hastens the recovery from dexmedetomidine-propofol-remifentanil anesthesia in patients undergoing uvulopalatopharyngoplasty, and may benefit patients with OSA.

Antinociceptive effects of dexmedetomidine via spinal substance P and CGRP.

The aim of this study was to examine the role played by substance P and calcitonin gene-related peptide (CGRP) within the dorsal horn of the spinal cord in engagement of antinociception evoked by dexmedetomidine (DEX). Paw withdrawal threshold (PWT) to mechanical stimulation was determined after chronic intrathecal infusion of DEX and enzyme-linked immunosorbent assay (ELISA) was employed to examine the levels of spinal substance P and CGRP. Our results show that PWT was significantly increased by intrathecal administration of DEX in rats (P < 0.05 vs. vehicle control, n = 20 in each group). Also, intrathecal infusion of DEX significantly decreased the concentrations of substance P and CGRP as compared with vehicle control (P < 0.05 DEX vs. vehicle control, n = 20 in each group). Blocking α2-adrenoreceptors (α2-AR) blunted the decreases of substance P and CGRP levels and the enhancement of PWT evoked by DEX. Additionally, a linear relationship was observed between PWT and the levels of spinal substance P (r = 0.87; P < 0.005) and CGRP (r = 0.85; P < 0.005). Moreover, blocking individual substance P and CGRP receptors amplified PWT without altering substance P and CGRP levels. Thus, DEX plays a role in stimulating α2-AR receptors, which thereby decreases substance P and CGRP levels within the dorsal horn. This contributes to DEX-evoked antinociception.

Intraoperative systemic lidocaine inhibits the expression of HMGB1 in patients undergoing radical hysterectomy.

Surgery stressors trigger inflammatory response and excessive inflammatory response leads to organ failure or even septic shock. HMGB1 as a later inflammatory cytokines and a critical mediator of severe sepsis is always associated with the aggravation of organ failure. Previous study shows that lidocaine can inhibit the expression of HMGB1 in macrophage of septic rats and protect animals from organ failure. The present study sought to determine whether intraoperative systemic lidocaine could attenuate the level of HMGB1 by inhibiting it expression in PBMC from patients underwent radical hysterectomy. Thirty patients were recruited and divided randomly into two groups according to the difference of study medicine. Patients in lidocaine group received an intravenous bolus infusion of 1.5 mg/kg of lidocaine followed by a continuous infusion of 1.5 mg/kg/h till discharged from operating room, and those in the control group received normal saline. Peripheral blood sample was drawn at pre-surgery, discharge from operating room and 48 h post-surgery. Monocytes were isolated and cultured with medium alone or with LPS. HMGB1 protein in serum or in supernatant of PBMC was detected with ELISA, while the HMGB1 mRNA in PBMC was determined by real-time quantitative PCR. The result showed that lidocaine not only attenuated the level of HMGB1 protein in serum and supernatant, but inhibited the transcription of HMGB1 mRAN in PBMC. The present study of us demonstrated that intraoperative systemic lidocaine can attenuate the level of HMGB1 and inhibit its expression in PBMC from patients underwent radical hysterectomy. Therefore, lidocaine may play an important role in many other clinical diseases by inhibiting HMGB1.

HMGB1 enhances smooth muscle cell proliferation and migration in pulmonary artery remodeling.

HMGB1 is a necessary and critical mediator of acute lung injury and can act as a chemoattractant and anti-apoptosis factor in injury or repair in diseases. In this study we sought to determine whether HMGB1 is involved in the remodeling of pulmonary artery and investigate the mechanism. A rat model of pulmonary artery remodeling was successful induced with LPS infusion and the increasing of pulmonary arteries media was obviously inhibited in rats treated with thrice inject of HMGB1 neutralizing antibody. The percent of areas of tunica media to total artery wall was (0.53 ± 0.15), (0.81 ± 0.10) and (0.59 ± 0.11) in control, LPS and antibody group respectively (p<0.05). Meanwhile, treatment with HMGB1 neutralizing antibody not only decreased the level of HMGB1 mRNA and protein significantly, but inhibited the expression of PCAN and Bcl-2 as well. On the contrary, Bax, a gen which represented the apoptosis, revealed an absolutely reversed trend to Bcl-2 in pulmonary arteries. Experiments in vitro showed that HMGB1 could stimulate the proliferation of hPASMC in MTT test and increase the number of migrated cells in a concentration-dependent manner in chemotaxis assay using modified Boyden chambers. In conclusion, data from this study support the concept that HMGB1 is involved in the remodeling of pulmonary artery by enhancing proliferation and migration of smooth muscle cell. Inhibiting HMGB1 may be a new target to deal with the remodeling of pulmonary artery.

Influence of polyvinyl chloride infusion extension tube on propofol injection pain: a randomised controlled study.

BACKGROUND: Propofol injection pain is a common and unsolved anaesthesia problem. OBJECTIVES: The present study attempted to confirm that the plasticiser di(2-ethylhexyl) phthalate in polyvinyl chloride (PVC) infusion tubes may increase propofol injection pain by increasing the aqueous propofol concentration. DESIGN: A randomised controlled study. SETTING: University teaching hospital, 1 April to 25 June 2013. PATIENTS: One hundred patients scheduled for elective surgery were allocated randomly to the PVC or the control (C) group. The PVC group received a propofol (Diprivan) infusion via a 1-m PVC infusion extension tube, whereas group C received propofol injected directly through the port of the cannula. INTERVENTION: After the syringe was loaded with propofol, air was expelled from the tube and the syringe was left standing for 5 min; intravenous propofol 0.5 mg kg was then injected either through the PVC tube or directly into the cannula. MAIN OUTCOME MEASURE: A verbal rating scale was used to evaluate the propofol injection pain in both groups. Di(2-ethylhexyl) phthalate and aqueous propofol concentrations were also measured in samples of propofol after simulated injection. To investigate whether the increase in aqueous propofol concentration was caused by leached di(2-ethylhexyl) phthalate, the same amount of di(2-ethylhexyl) phthalate as that measured in the PVC group was added to the samples (group D). RESULTS: The incidences of pain in groups PVC and C were 88 and 46%, respectively (P < 0.0001). The di(2-ethylhexyl) phthalate concentration in group PVC (1.01 ±â€Š0.07 µg ml) was greater than that in group C (lower than the detection limit of 0.03 µg ml). No significant difference was found between the aqueous propofol concentrations in groups PVC (25.9 ±â€Š1.8 µg ml) and D (24.4 ±â€Š1.1 µg ml) (P = 0.22), which were significantly higher than that in group C (14.3 ±â€Š1.0 µg ml) (P = 0.079). CONCLUSION: Propofol injection pain is increased by contact with PVC infusion tubing as a result of an increase in aqueous propofol concentration caused by di(2-ethylhexyl) phthalate leaching into the lipid emulsion. TRIAL REGISTRATION: chictr.org identifier: ChiCTR-TRC-12003170.

The protective effect of lidocaine on septic rats via the inhibition of high mobility group box 1 expression and NF-κB activation.

Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF- κB.

The inhibitory effect of lidocaine on the release of high mobility group box 1 in lipopolysaccharide-stimulated macrophages.

BACKGROUND: High mobility group box 1 (HMGB1), a key mediator of inflammation, has been shown to inhibit phagocytosis of apoptotic cells in sepsis. Lidocaine has been proven to protect macrophages in mice with septic peritonitis by attenuating the production of cytokines. However, it is currently unknown whether lidocaine also affects HMGB1. In this study, we sought to detect the effect of lidocaine on the release of HMGB1 from RAW264.7 macrophages after lipopolysaccharide (LPS) stimulation. METHODS: The levels of HMGB1 in the supernatant of RAW264.7 cells incubated with LPS and different concentrations of lidocaine were measured by enzyme-linked immunosorbent assays. HMGB1 mRNA expression was assessed by real-time polymerase chain reaction. The immunocytochemistry was used to detect the release and translocation of HMGB1 from the nucleus to cytoplasm. Nuclear factor (NF)-κB levels in the nuclear fraction of RAW264.7 cells were measured with the Active Motif NF-κB family kit. RESULTS: We found that lidocaine suppressed the translocation of HMGB1 from the nucleus to cytoplasm and decreased the expression of HMGB1 mRNA in RAW264.7 cells induced by LPS. Furthermore, the LPS-stimulated translocation of NF-κB from the cytoplasm to nucleus was inhibited by lidocaine in a dose-dependent manner. CONCLUSIONS: Our data suggest that lidocaine functions as an antiinflammatory by inhibiting expression of HMGB1 mRNA, and translocating both HMGB1 and NF-κB from the nucleus to cytoplasm. The mechanism of these effects might be involved, at least partly, in the inhibition of the NF-κB signal pathway.