Weifeng Yu

Remifentanil Preconditioning Reduces Hepatic Ischemia― Reperfusion Injury in Rats via Inducible Nitric Oxide Synthase Expression

BACKGROUND Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms. METHODS A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, L-arginine and N-ω-nitro-L-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated. RESULTS Remifentanil and L-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-L-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and L-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-L-arginine methyl ester groups. CONCLUSION Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response.

From QUOROM to PRISMA: A Survey of High-Impact Medical Journals' Instructions to Authors and a Review of Systematic Reviews in Anesthesia Literature

Background The PRISMA (Preferred Reporting Items of Systematic reviews and Meta-Analyses) Statement was published to help authors improve how they report systematic reviews. It is unknown how many journals mention PRISMA in their instructions to authors, or whether stronger journal language regarding use of PRISMA improves author compliance. Methodology/Principal Findings An Internet-based investigation examined the extent to which 146 leading medical journals have incorporated the PRISMA Statement into their instructions to authors. Results were analyzed using descriptive statistics. Also, systematic reviews published in the leading anesthesiology journals and the QUOROM (QUality Of Reporting Of Meta-analyses) Statement were used to explore the hypothesis that indicating compliance with the QUOROM Statement in the manuscript is associated with improved compliance with the reporting guideline. In a sample of 146 journals publishing systematic reviews, the PRISMA Statement was referred to in the instructions to authors for 27% (40/146) of journals; more often in general and internal medicine journals (7/14; 50%) than in specialty medicine journals (33/132; 25%). In the second part of the study, 13 systematic reviews published in the leading anesthesiology journals in 2008 were included for appraisal. Mention of the QUOROM Statement in the manuscript was associated with higher compliance with the QUOROM checklist (P = 0.022). Conclusions/Significance Most of the leading medical journals used ambiguous language regarding what was expected of authors. Further improvement on quality of reporting of systematic reviews may entail journals clearly informing authors of their requirements. Stronger directions, such as requiring an indication of adherence to a research quality of reporting statement in the manuscript, may improve reporting and utility of systematic reviews.

Controlled low central venous pressure reduces blood loss and transfusion requirements in hepatectomy

AIM To evaluate the effect of low central venous pressure (LCVP) on blood loss and blood transfusion in patients undergoing hepatectomy. METHODS Electronic databases and bibliography lists were searched for potential articles. A meta-analysis of all randomized controlled trials (RCTs) investigating LCVP in hepatectomy was performed. The following three outcomes were analyzed: blood loss, blood transfusion and duration of operation. RESULTS Five RCTs including 283 patients were assessed. Meta-analysis showed that blood loss in the LCVP group was significantly less than that in the control group (MD = -391.95, 95%CI: -559.35--224.56, P < 0.00001). In addition, blood transfusion in the LCVP group was also significantly less than that in the control group (MD = -246.87, 95%CI: -427.06--66.69, P = 0.007). The duration of operation in the LCVP group was significantly shorter than that in the control group (MD = -18.89, 95%CI: -35.18--2.59, P = 0.02). Most studies found no significant difference in renal and liver function between the two groups. CONCLUSION Controlled LCVP is a simple and effective technique to reduce blood loss and blood transfusion during liver resection, and appears to have no detrimental effects on liver and renal function.

Isoflurane Preconditioning at Clinically Relevant Doses Induce Protective Effects of Heme Oxygenase-1 on Hepatic Ischemia Reperfusion in Rats

BackgroundActivation of heme oxygenase-1 (HO-1) has been proved to reduce damages to the liver in ischemia reperfusion injury. The objective of present study was to determine whether clinic relevant doses of isoflurane treatment could be sufficient to activate HO-1 inducing, which confers protective effect against hepatic ischemia-reperfusion injury.MethodsThe hepatic artery and portal vein to the left and the median liver lobes of forty male Sprague-Dawley rats were occluded for 60 minutes. Reperfusion was allowed for 4 hours before the animal subjects were sacrificed. Six groups (n = 12) were included in the study. A negative control group received sham operation and positive control group a standard ischemia-reperfusion regimen. The third group was pretreated with isoflurane prior to the ischemia-reperfusion. The fourth group received an HO-1 inhibitor zinc protoporphyrin (Znpp) prior to the isoflurane pretreatment and the ischemia-reperfusion. The fifth group received Znpp alone before ischemia-reperfusion procedure, and the sixth group was administrated with a HO-1 inducer hemin prior to IR. HO-1 in the liver was measured using an enzymatic activity assay, a Western blot analysis, as well as immunohistochemical method. Extent of liver damage was estimated by determination of the serum transaminases, liver lipid peroxidation and hepatic histology. Infiltration of the liver by neutrophils was measured using a myeloperoxidase activity assay. TNFα mRNA in the liver was measured using RT-PCR.ResultsIsoflurane pretreatment significantly attenuated the hepatic injuries and inflammatory responses caused by the ischemia reperfusion. Selectively inhibiting HO-1 with ZnPP completed blocked the protective effects of isoflurane. Inducing HO-1 with hemin alone produced protective effects similar in magnitude to that of isoflurane.ConclusionsClinic relevant doses of isoflurane attenuate ischemia reperfusion injury in rats by increasing the HO-1 expression and activity.

A Comparison of Liver Function After Hepatectomy with Inflow Occlusion Between Sevoflurane and Propofol Anesthesia

BACKGROUND:In this study, we compared liver function tests after hepatectomy with inflow occlusion as a function of propofol versus sevoflurane anesthesia. METHODS:One hundred patients undergoing elective liver resection with inflow occlusion were randomized into a sevoflurane group or a propofol group. General anesthesia was induced with 3 &mgr;g/kg fentanyl, 0.2 mg/kg cisatracurium, and target-controlled infusion of propofol, set at a plasma target concentration of 4 to 6 &mgr;g/mL, or sevoflurane initially started at 8%. Anesthesia was maintained with target-controlled infusion of propofol (2–4 &mgr;g/mL) or sevoflurane (1.5%–2.5%). The primary end point was postoperative liver injury assessed by peak values of liver transaminases. RESULTS:Transaminase levels peaked between the first and the third postoperative day. Peak alanine aminotransferase was 504 and 571 U/L in the sevoflurane group and the propofol group, respectively. Peak aspartate aminotransferase was 435 U/L after sevoflurane and 581 U/L in the propofol group. There were no significant differences in peak alanine aminotransferase or peak aspartate aminotransferase between groups. Other liver function tests including bilirubin and alkaline phosphatase, and peak values of white blood cell counts and creatinine, were also not different between groups. CONCLUSIONS:Sevoflurane and propofol anesthetics resulted in similar patterns of liver function tests after hepatectomy with inflow occlusion. These data suggest that the 2 anesthetics are equivalent in this clinical context.

Involvement of RVM-expressed P2X7 receptor in bone cancer pain: Mechanism of descending facilitation

Summary This study highlights the supraspinal glial mechanism underlying the induction of bone cancer pain and provides a new potential target for the treatment of cancer pain. ABSTRACT Patients with bone cancer commonly experience bone pain that is severe, intolerable, and difficult to manage. The rostral ventromedial medulla (RVM) plays an important role in the development of chronic pain via descending facilitation of spinal nociception. The compelling evidence shows that glial P2X7 receptor (P2X7R) is involved in the induction and maintenance of chronic pain syndromes. The present study explored the mechanism of glial activation and P2X7R expression underlying the induction of bone cancer pain. The results demonstrated that microglia and astrocytes in the RVM were markedly activated in bone cancer rats, and the expression of P2X7R was significantly upregulated. Injection of Brilliant Blue G (BBG), an inhibitor of P2X7R, into the RVM significantly alleviated pain behaviors of cancer rats, which was supported by intra‐RVM injection of RNA interference targeting the P2X7R in the RVM. It is suggested that activation of microglia‐expressed P2X7R in the RVM contributes to bone cancer pain. Given that 5‐HT in the RVM is involved in modulating spinal nociception, changes in 5‐HT and Fos expression were addressed in the spinal cord. Inhibition of P2X7R by BBG or small‐interference RNA targeting P2X7 in the RVM markedly reduced 5‐HT level and Fos expression in the spinal cord. The data clearly suggest that the activation of microglial P2X7R in the RVM contributes to the development of bone cancer pain via upregulation of spinal 5HT levels by the descending pain facilitatory system.

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release

BackgroundThe nuclear protein high-mobility group box 1 (HMGB1) is a key trigger for the inflammatory reaction during liver ischemia reperfusion injury (IRI). Hydrogen treatment was recently associated with down-regulation of the expression of HMGB1 and pro-inflammatory cytokines during sepsis and myocardial IRI, but it is not known whether hydrogen has an effect on HMGB1 in liver IRI.MethodsA rat model of 60 minutes 70% partial liver ischemia reperfusion injury was used. Hydrogen enriched saline (2.5, 5 or 10 ml/kg) was injected intraperitoneally 10 minutes before hepatic reperfusion. Liver injury was assessed by serum alanine aminotransferase (ALT) enzyme levels and histological changes. We also measured malondialdehyde (MDA), hydroxynonenal (HNE) and 8-hydroxy-guanosine (8-OH-G) levels as markers of the peroxidation injury induced by reactive oxygen species (ROS). In addition, pro-inflammatory cytokines including TNF-α and IL-6, and high mobility group box B1 protein (HMGB1) were measured as markers of post ischemia-reperfusion inflammation.ResultsHydrogen enriched saline treatment significantly attenuated the severity of liver injury induced by ischemia-reperfusion. The treatment group showed reduced serum ALT activity and markers of lipid peroxidation and post ischemia reperfusion histological changes were reduced. Hydrogen enriched saline treatment inhibited HMGB1 expression and release, reflecting a reduced local and systemic inflammatory response to hepatic ischemia reperfusion.ConclusionThese results suggest that, in our model, hydrogen enriched saline treatment is protective against liver ischemia-reperfusion injury. This effect may be mediated by both the anti-oxidative and anti-inflammatory effects of the solution.

Citation classics in main pain research journals.

The number of citations of an article in scientific journals reflects its impact on a specific biomedical field and its recognition in the scientific community. In the present study, we identified and analyzed the characteristics of the 100 most frequently cited articles published between 1970 and 2010 in journals pertaining to pain research and related fields. These articles were identified using the database of the Science Citation Index (1970 to present). The most cited article received 3,017 citations and the least cited article received 302 citations, with a mean of 585 citations per article. These citation classics were published in six high-impact journals, led by Pain (84 articles). Of the 100 articles, 39 were observational studies, 25 were review articles, and 20 concerned basic science. The articles originated from 14 countries, with the United States contributing 47 articles; 67 institutions produced these 100 top-cited articles, led by National Institutes of Health of the United States (8 articles) and University College London (6 articles); 18 persons authored 2 or more of the top-cited articles. This analysis of the top citation classics allows for the recognition of major advances in pain research and gives a historical perspective on the scientific progress of this specialty.

Small Interference RNA Targeting TLR4 Gene Effectively Attenuates Pulmonary Inflammation in a Rat Model

Objective. The present study was to investigate the feasibility of adenovirus-mediated small interference RNA (siRNA) targeting Toll-like receptor 4 (TLR4) gene in ameliorating lipopolysaccharide- (LPS-) induced acute lung injury (ALI). Methods. In vitro, alveolar macrophages (AMs) were treated with Ad-siTLR4 and Ad-EFGP, respectively, for 12 h, 24 h, and 48 h, and then with LPS (100 ng/mL) for 2 h, and the function and expression of TLR4 were evaluated. In vivo, rats received intratracheal injection of 300 μL of normal saline (control group), 300 μL of Ad-EGFP (Ad-EGFP group), or 300 μL of Ad-siTLR4 (Ad-siTLR4 group) and then were intravenously treated with LPS (50 mg/kg) to induce ALI. Results. Ad-siTLR4 treatment significantly reduced TLR4 expression and production of proinflammatory cytokines following LPS treatment both in vitro and in vivo. Significant alleviation of tissue edema, microvascular protein leakage, and neutrophil infiltration was observed in the AdsiTLR4-treated animals. Conclusion. TLR4 plays a critical role in LPS-induced ALI, and transfection of Ad-siTLR4 can effectively downregulate TLR4 expression in vitro and in vivo, accompanied by alleviation of LPS-induced lung injury. These findings suggest that TLR4 may serve as a potential target in the treatment of ALI and RNA interfering targeting TLR4 expression represents a therapeutic strategy.

Awakening Concentration of Desflurane Is Decreased in Patients with Obstructive Jaundice

Background:Some studies suggest that behavioral complications of cholestasis, such as fatigue and pruritus, may be associated with altered neurotransmission in the brain. Because inhaled anesthetics primarily act on ion channels and receptors on the neuronal cell membrane and alter synaptic transmission in the central nervous system, it is possible that altered sensitivity to inhaled anesthetics may occur in cholestatic patients. Therefore, the authors compared the minimum alveolar concentration (MAC)-awake of desflurane in obstructive jaundiced patients with the MACawake in nonjaundiced patients. Methods:Patients underwent inhalational induction of anesthesia with desflurane. MACawake was determined in each patient by observing the response to a verbal command (open eyes on request). An end-tidal anesthetic concentration was maintained at an initial target level of 1.4% for 15 min before a command. If a positive response was observed, the concentration of desflurane was increased by 0.1% and again kept constant for 15 min. The verbal command was then continued. This process was repeated until an end-tidal concentration was reached at which the patient did not respond to command. The anesthetic concentration midway between the value permitting the response and that just preventing the response was defined as MACawake for each patient. Results:The MACawake of desflurane for patients with obstructive jaundice (1.78 ± 0.19%) was significantly less than those observed for the control group (2.17 ± 0.25%; P < 0.001) and correlated significantly with serum total bilirubin (r = −0.67, P = 0.0004). Conclusions:The MACawake of desflurane is reduced in obstructive jaundiced patients compared with nonjaundiced controls.