[Show abstract][Hide abstract] ABSTRACT: Background:
The CONCERT-CL closed-loop infusion system designed by VERYARK Technology Co., Ltd. (Guangxi, China) is an innovation using TCI combined with closed-loop controlled intravenous anesthesia under the guide of BIS. In this study we performed a randomized, controlled, multicenter study to compare closed-loop control and open-loop control of propofol by using the CONCERT-CL closed-loop infusion system.
180 surgical patients from three medical centers undergone TCI intravenous anesthesia with propofol and remifentanil were randomly assigned to propofol closed-loop group and propofol opened-loop groups. Primary outcome was global score (GS, GS = (MDAPE+Wobble)/% of time of bispectral index (BIS) 40-60). Secondary outcomes were doses of the anesthetics and emergence time from anesthesia, such as, time to tracheal extubation.
There were 89 and 86 patients in the closed-loop and opened-loop groups, respectively. GS in the closed-loop groups (22.21±8.50) were lower than that in the opened-loop group (27.19±15.26) (p=0.009). The higher proportion of time of BIS between 40 and 60 was also observed in the closed-loop group (84.11±9.50%), while that was 79.92±13.17% in the opened-loop group, (p=0.016). No significant differences in propofol dose and time of tracheal extubation were observed. The frequency of propofol regulation in the closed-loop group (31.55±9.46 times/hr) was obverse higher than that in the opened-loop group (6.84±6.21 times/hr) (p=0.000).
The CONCERT-CL closed-loop infusion system can automatically regulate the TCI of propofol, maintain the BIS value in an adequate range and reduce the workload of anesthesiologists better than open-loop system.
PLoS ONE 04/2015; 10(4):e0123862. DOI:10.1371/journal.pone.0123862 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Supraventricular tachycardia during the induction of anesthesia may carry a higher risk.Study objectiveThe aim of this study was to evaluate efficacy and safety of intravenous landiolol in Chinese patients with intraoperative supraventricular tachycardia during anesthesia.DesignA randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase 2 study.SettingEight sites of Chinese hospitals.PatientsMen and women aged 18 to 70 years with the intraoperative supraventricular tachycardia (heart rate [HR], ≥ 100 beats/min) or the supraventricular tachycardia outside of the sinus tachycardia lasting more than 1 minute.InterventionsPatients received landiolol or placebo—0.125 mg kg− 1 min− 1 (1 minute) loading→0.04 mg kg− 1 min− 1 (10 minutes) continuous.MeasurementsThe proportion of patients receiving rescue medication (esmolol) when the reduction of HR did not exceed 10% after intravenous landiolol for 5 minutes. Other secondary efficacy end points include HR, blood pressure, rate pressure product, and electrocardiogram; the improvement of supraventricular tachycardia; the time it takes for the decrease of the HR to reach more than 10%; and the time it takes for the HR to reach < 100 beats/min.Main resultsEfficacy and safety were evaluated for 240 patients who received study drug. Lower proportions of patients received rescue medication in the landiolol group (7.63%) compared with that in the placebo group (80.33%) (P < .0001). Suppression of HR and rate pressure product was generally more potent(P < .0001), and higher proportions of patients improved supraventricular tachycardia (P < .0001) in the landiolol group. The most frequent adverse event was hypotension.Conclusion
Intravenous landiolol (loading dose of 0.125 mg/kg) may effectively control intraoperative supraventricular tachycardia during anesthesia. It inhibited the increases in HR during the induction of anesthesia. The effect of landiolol on blood pressure was minimal without decreasing diastolic blood pressure and with the minor reduction of systolic blood pressure (ClinicalTrials.gov number, ChiCTR-TRC-12003021).
[Show abstract][Hide abstract] ABSTRACT: A classic general anesthesia is performed by induction with an intravenous hypnotic (such as propofol) and maintenance with a volatile anesthetic (such as sevoflurane). The aim of the present study was to compare the effects of a propofol/sevoflurane maintenance regimen with that of a sevoflurane regimen on recovery profiles.
One hundred and sixty patients, who were ASA 1 or 2, 45-65 years of age, and scheduled for elective gastrointestinal surgery under combined general/epidural anesthesia, were allocated randomly to receive the sevoflurane maintenance regimen (group S, n = 80) or sevoflurane/propofol regimen (group SP, n = 80). After induction, anesthesia was maintained with sevoflurane in group S and sevoflurane with propofol (1.2 μg/ml target plasma concentration) in group SP. Bispectral index (BIS) values were maintained within 40-60 during the maintenance. Time to extubation, incidence of serious coughing and agitation, and other recovery characteristics were evaluated during emergence.
The time to awakening and extubation in group SP were 7.2 ± 2 min and 8.0 ± 1.8 min, respectively, which were shorter than those results in group S (12.3 ± 1.5 and 12.8 ± 1.6 min, respectively) (P < 0.05). The incidence of serious coughing and agitation in SP (30 % and 25 %) was lower than that of group S (68 % and 53 %) (P < 0.05). BIS value, pain score, requirements of analgesics and antiemetics in the PACU, and length of stay in the PACU were similar in the two groups.
Compared to sevoflurane maintenance, coadministration of propofol and sevoflurane provides faster awakening and extubation with a low incidence of emergence coughing and agitation.
Journal of Anesthesia 02/2014; 28(5). DOI:10.1007/s00540-014-1803-0 · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postoperative shivering is a frequent complication of surgery in developing countries and there is no satisfying method to treat it, let alone to cure it. We studied whether intravenous amino acid (AA) infusion can cure postoperative shivering in the postanesthesia care unit.
Sixty postanesthesia care unit patients with shivering grade 2 or higher and tympanic temperature <36°C received randomly either infusion of Novamin 18 AAs (2 mL/kg/h), pethidine (0.5 mg/kg), or tramadol (1 mg/kg). Tympanic temperature, shivering grade, and thermal comfort were assessed every 5 min for 60 min. Blood glucose and lactic acid concentrations were measured before and after treatment. Postoperative nausea and vomiting were also recorded.
Shivering stopped within 5 min in the pethidine and tramadol groups versus 90% stopped within 15 min in AA group. There were five cases of reshivering in the tramadol group versus none in the AA or pethidine groups. Tympanic temperature increased slowly in all patients but increased significantly faster in the AA group. Thermal comfort improved significantly faster in the AA group versus the other two groups, thermal comfort was significantly higher in the tramadol versus the pethidine group ≥35 min. Blood glucose concentration in AA group increased to 135.18 ± 9.18 mg/dL. There were some cases of nausea and vomiting in pethidine and tramadol groups but none in the AA group.
Novamin infusion can stop postoperative shivering and alleviates hypothermia and improves thermal comfort more effectively than tramadol and pethidine with less nausea and vomiting and causes a clinically acceptable blood glucose increase with no reshivering episodes.
Journal of Surgical Research 12/2013; 188(1). DOI:10.1016/j.jss.2013.11.1117 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
To investigate the protective effects of propofol in brain ischemia/reperfusion injury and the role of heme oxygenase-1 (HO-1) in this process.
Sprague-Dawley rats were randomly divided into 9 groups: sham-operated group; middle cerebral artery occlusion (MCAO) group; propofol 10, 20, and 50 mg/kg/h group (propofol 10, 20, 50 mg/kg/h infused at the onset of reperfusion for 30 min), ZnPPIX (a HO-1 activity inhibitor) group (ZnPPIX 20 μmol/kg administered 24 h before MCAO), and the other 3 groups received ZnPPIX followed by 10, 20, and 50 mg/kg/h propofol respectively. At 24 hours of reperfusion, neurological examinations were performed, and after neurological test, brain infarct size and volume, neuronal apoptosis, the level of HO-1 protein expression and HO-1 activity were observed in each group.
Propofol significantly improved neurological deficits, reduced infarct volume, and attenuated neuron apoptosis compared with MCAO group alone. Increased HO-1 protein expression was observed in the ischemic penumbra and core of propofol group after transient MCAO. The selective HO-1 activity inhibitor, ZnPPIX, partially eliminated the neuroprotective effects of propofol.
The neuroprotective effects of propofol postconditioning in brain ischemia/reperfusion injury may be partially through the induction of the HO-1 expression.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Stepwise propofol target-controlled infusion (TCI) can achieve a less disturbed condition of hemodynamics and respiration. Its combination with dexmedetomidine may have some advantages for patients. We studied the effects of different loading doses of dexmedetomidine on the bispectral index (BIS) under stepwise propofol TCI.
Forty patients were randomly assigned into groups D(1.0), D(0.5), D(0.25) and D(0), in which dexmedetomidine at 1.0, 0.5, 0.25 or 0 µg•kg(-1) was infused over 10 min followed by 0.5 µg•kg(-1)•h(-1) and stepwise propofol TCI, which was administered with target effect site concentration (Ce) at 0.5 µg•ml(-1), and increased until 2.5 µg•ml(-1) by 1.0 µg•ml(-1) after 5 min reaching target Ce. BIS, heart rate, MAP, pulse oxygen saturation, RR and end-tidal carbon dioxide pressure were recorded before loading dose (T(0)), at 5 min (T(5 min)) and 10 min (T(10 min)) after starting infusion, after 5 min reaching Ce of 0.5, 1.5 and 2.5 µg•ml(-1) (T(p0.5), T(p1.5) and T(p2.5)).
BIS values in group D(1.0) were significantly lower compared with those in group D(0) since T(10 min) and those in groups D(0.5) and D(0.25) since T(p0.5). In group D(1.0), heart rate decreased significantly at T(5 min) and T(10 min), heart rate at T(10 min) was significantly lower compared with that in group D(0). MAP remained stable during the loading dose infusion and decreased to some degree after propofol infusion in all groups. Changes in pulse oxygen saturation, RR and end-tidal carbon dioxide pressurewere similar among the groups without respiration depression.
A loading dose of dexmedetomidine of 1.0 µg•kg(-1), not 0.5 µg•kg(-1) or less, over 10 min followed by 0.5 µg•kg(-1)•h(-1) can definitely decrease the BIS under stepwise propofol TCI with clinically stable blood pressure and without respiration depression, while attention should be paid to decreased heart rate.
[Show abstract][Hide abstract] ABSTRACT: Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain. The present study was carried out to investigate the effects of sevoflurane on neurogenesis, neurodegeneration and behavior.
We administered 5-bromodeoxyuridine, an S-phase marker, before, during, and after 4 h of sevoflurane given to rats on postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade staining for degeneration. Spatial reference memory was tested 2 and 6 weeks after anesthesia.
Sevo-flurane decreased progenitor proliferation and increased cell death until at least 4 days after anesthesia. Spatial reference memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane administration.
Sevoflurane reduces neurogenesis and increases the death of progenitor cells in developing brain. This might mediate the late-onset neurocognitive outcome after sevoflurane application.
[Show abstract][Hide abstract] ABSTRACT: Background:
Intraoperative amino acid infusion can attenuate the decrease in core temperature, but the metabolic effects are uncertain.
Thirty-six healthy mongrel dogs undergoing ileectomy under general anesthesia were infused intraoperatively with normal saline or 18 compound amino acids at 6, 12, and 24 kJ·kg⁻¹·h⁻¹ (NS, 6-, 12-, and 24-kJ groups) and studied until 24 h after the operation. Blood glucose, plasma insulin, free fatty acids, and triglyceride concentrations were determined at 7 defined time points. Muscle aminograms, urinary urea, and 3-methylhistidine excretions were measured before and after the operation.
Blood glucose and plasma insulin increased amino acid dose dependently during the operation and in the early period after the operation. Free fatty acids were significantly lower in the 12- and 24-kJ groups compared with the NS group at the end of the operation. The negative nitrogen balance was alleviated dose dependently in the amino acid groups on operation day. The urinary 3-methylhistidine decreased significantly during the first 24 h after the operation in the 24-kJ group, while it increased in the other groups with the largest increase in the NS group. Basic, branched-chain, and aromatic amino acids in the vastus lateralis muscle increased dose dependently at the end of the operation in the amino acid groups.
Intraoperative amino acid infusion has the dose-dependent effects of increasing blood glucose, inhibiting fat mobilization and muscle protein breakdown.
Annals of Nutrition and Metabolism 08/2012; 61(2):117-125. DOI:10.1159/000341566 · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients.
Neurobiology of Disease 07/2012; 48(3):348-55. DOI:10.1016/j.nbd.2012.06.022 · 5.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ischemia reperfusion (IR) is a frequent pathological injury to the perioperative patients. The molecular mechanism underlying IR injury is still not well characterized. In this study, we investigated the effect of IR injury on DNA hydroxymethylation in mouse kidney. Dot blot and immunochemistry analysis showed that the global level of 5-hydroxymethylcytosine (5hmC) was reduced in mouse kidney insulted by IR; however, the 5-methylcytosine (5mC) level had no significant change. hMeDIP-qPCR validated that IR injury also decreased the 5hmC enrichment at promoter regions of Cxcl10 and Ifngr2 genes. RT-qPCR analysis revealed that the mRNA levels of Cxcl10 and Ifngr2 increased in IR-injured kidney. In addition, mRNA expression of both Tet1 and Tet2 but not Tet3 was dramatically downregulated in IR-injured kidney. Taken together, our data provided the first evidence that IR injury influences DNA hydroxymethylation and Tet gene expression in mouse kidney, which may contribute to the regulation of gene transcription during renal IR injury.
Biochemical and Biophysical Research Communications 05/2012; 422(4):697-702. DOI:10.1016/j.bbrc.2012.05.061 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this trial was to compare the Enhanced Recovery After Surgery (ERAS) program with conventional perioperative management in patients who underwent radical resection for colorectal cancer.
A combination of evidence-based and consensus methodology was used to develop the ERAS protocol. Five hundred ninety-seven consecutive patients who underwent elective colorectal resection were randomized to either the ERAS (n = 299) or the control group (n = 298). Outcomes relating to nutrition and metabolism index, stress index, and recovery index were measured and recorded.
Demographic and operative data were similar between the two groups. Patients in the ERAS group showed improved nutritional status when compared with those of the control group. On postoperative day (POD) 1, the HOMA-IR (insulin resistance index) of the ERAS group was lower than that of the control group (p < 0.001). The cortisol level of the control group was elevated on both POD 1 (p = 0.007) and POD 5 (p = 0.002) compared to the preoperative level. However, the cortisol level of the ERAS group was not increased until POD 5 (p = 0.001). Reduced levels of TNF-α, IL-1β, IL-6, and IFN-γ in the ERAS group indicated less postoperative stress responses. In addition, ERAS was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay (p < 0.001) and expense (p < 0.001) for the ERAS group were reduced in comparison to the controls. Twenty-eight cases in the control group and twenty-nine in the ERAS group suffered complications, which was not significantly different.
The ERAS protocol attenuates the surgical stress response and accelerates postoperative recovery without compromising patient safety.
World Journal of Surgery 11/2011; 36(2):407-14. DOI:10.1007/s00268-011-1348-4 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study was designed to investigate the possible effect of chronic alcohol intake on propofol and remifentanil requirements, which was determined by quantifying the 50% (EC(50) ) and 95% (EC(95) ) effective effect-site concentrations for propofol and remifentanil at loss of consciousness (LOC) and after a painful stimulus.
Thirty male patients (alcoholic group; n = 30) with chronic alcoholism and 30 patients (control group; n = 30) with a history of small alcohol intake were anaesthetized with propofol and remifentanil by target-controlled infusion. The predicted drug concentrations and Bispectral Index (BIS) values were recorded at LOC and after no response to painful stimuli.
The EC(50) and EC(95) of propofol at LOC in alcoholic group were 3.15 [95% confidence interval (CI), 2.77-3.37] and 4.05 (95% CI, 3.18-5.26) μg/ml, respectively, and those of the control group were 2.21 (95% CI, 1.92-2.86) and 3.04 (95% CI, 2.45-4.64) μg/ml, respectively. The EC(50) and EC(95) of remifentanil measured after no response to painful stimuli in the alcoholic group were 3.02 (95% CI, 2.70-3.38) and 4.98 (95% CI, 4.56-5.89) ng/ml, respectively, and those of the control group were 2.95 (95% CI, 2.68-3.33) and 4.86 (95% CI, 4.55-5.92) ng/ml, respectively. The EC(50) and EC(95) values of propofol at LOC in the control group were significantly lower than that of the alcoholic group.
These findings suggest that the induction dose requirements of propofol are increased in alcoholic patients anaesthetized with propofol and remifentanil administered by target controlled infusion.
[Show abstract][Hide abstract] ABSTRACT: Heme oxygenase-1 (HO-1) is an important cytoprotective agent. We examined the effect of propofol on the regulation of HO-1 expression and its activity in human umbilical vein endothelial cells (HUVECs) under oxidative stress conditions. We further assessed whether extracellular signal-regulated kinases (ERKs), cJun-N-terminal kinases (JNKs), and p38-mitogen-activated protein kinase mediate propofol-induced HO-1 expression.
Hydrogen peroxide (100 μmol/L) was used to induce oxidative stress. HUVECs were treated with different concentrations (1025 and 50 μmol/L) of propofol for various periods of time. Finally, cells were pretreated with SB203580 (10 μmol/L), a p38-mitogen-activated protein kinase inhibitor; PD98059 (25 μmol/L), an ERKs inhibitor; SP600125 (10 μmol/L), a JNKs inhibitor; and ZnPPIX (10 μmol/L), an HO-1 activity inhibitor, followed by propofol incubation. Reverse transcriptase polymerase chain reaction was used to detect HO-1 mRNA expression. HO-1 activity was determined in microsomal fractions from HUVECs by monitoring the conversion of heme into bilirubin. HO-1 protein and phosphorylated ERKs were measured by western blot analysis. Cell apoptosis was detected using terminal transferase deoxyuridine triphosphate-biotin nick-end labeling.
Under oxidative stress conditions, HO-1 expression and activity were increased by propofol in a dose-dependent and time-dependent manner. PD98059, but not SB203580 or SP600125, effectively reduced propofol-induced HO-1 protein levels. The phosphorylation of ERKs was significantly increased by propofol, and this process was also inhibited by PD98059. Hydrogen peroxide-induced apoptosis in HUVECs was attenuated by propofol, which was partly reversed by ZnPPIX.
These findings show that, under oxidative stress conditions, propofol induces HO-1 expression in HUVECs and this effect is mediated, at least in part, via ERKs pathways.
[Show abstract][Hide abstract] ABSTRACT: Dimethyl sulfoxide (DMSO) has recently been proposed as an anti-inflammatory and free radical scavenging agent. However, the mechanisms by which DMSO mediates its therapeutic effects are unclear. In this paper, we investigated the capability of DMSO to up-regulate heme oxygenase-1(HO-1) expression, as well as the possible underlying mechanisms in human umbilical vein endothelial cells (HUVECs). DMSO induced HO-1 expression both at the level of mRNA and protein in dose-and time-dependent manners in HUVECs, resulting in increased HO-1 activity. The pharmacological inhibition of cJun-N-terminal kinases (JNKs) blocked the DMSO-induced HO-1 up-regulation, while inhibition of extracellular regulated kinase and p38-MAPK did not block heme oxygenase-1 up-regulation. In addition, the phosphorylation of JNKs was initiated by DMSO, indicating the involvement of this kinase in the observed response. DMSO increased the nuclear translocation of NF-E2-related factor 2 (Nrf2) and enhanced its binding to the anti-oxidant response element. Inhibition of Nrf2 synthesis by small interfering RNA molecules subsequently inhibited HO-1 expression induced by DMSO, indicating DMSO's role in inducing HO-1 expression via Nrf2 activation. Utilizing these findings, the present study identified DMSO as a novel inducer of HO-1 expression and identified the underlying mechanisms involved in this process.
[Show abstract][Hide abstract] ABSTRACT: The effect of general anesthetics on the developing brain is receiving growing attention. Nonetheless, there remains a paucity of evidence regarding the effect of sevoflurane, a widely used anesthetic in pediatric anesthesia. This study was designed to investigate the effect of sevoflurane on nerve cell apoptosis in the developing brain. Techniques to detect cell apoptosis included immunohistochemistry of cleaved caspase-3 and single-strand DNA, as well as electron microscopy. Elevated cleaved caspase-3 was also validated semi-quantitatively by immunoblotting assay. Mouse pups (day 7 postnatal) were subjected to sevoflurane inhalation. Twelve hours later, dramatically increased cleaved caspase-3 and single-strand DNA immunoreactivity were detected in the pup brains. Immunoblotting assay of cleaved caspase-3 revealed a significant increase after anesthetic exposure. Electron microscopy disclosed typical apoptotic morphology of the degenerative nerve cells. Blood glucose levels in the anesthetized group were not different from those of the control group, indicating that the neuronal apoptosis observed in the anesthetized group was not the result of hypoglycemia. Our results indicate that subanesthetic concentration of sevoflurane can trigger neuronal apoptosis in the postnatal mouse brain.
[Show abstract][Hide abstract] ABSTRACT: Propofol protects cells against ischemia/reperfusion injury in several organs, but there are few reports of its effect on liver epithelial cells. We investigated the effect of propofol preconditioning on human hepatic L02 cells under hydrogen peroxide (H2O2)-induced oxidative stress and attempted to determine whether the extracellular signal-regulated kinases (ERK) pathway is involved in this process.
Preconditioned or nonpreconditioned human hepatic L02 cells were exposed to H2O2 and the changes of apoptosis were evaluated by TUNEL assay, Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage. Activation of ERK1/2 and mitogen-activated protein kinase//ERK Kinase 1/2 (MEK1/2) was measured by Western blot analysis. The mRNA expression of Bcl-2, Bcl-x(L), Bad, and Bax was quantified by real-time quantitative reverse transcriptase polymerase chain reaction.
Propofol preconditioning reduced the population of apoptotic cells and Caspase-3 and PARP cleavage induced by H2O2 inhepatic L02 cells. L02 cells treated with propofol (0.01-0.3 mM) alone, led to a dose-dependent activation of ERK and MEK, and such activation was detected within 0.5 h and eventually declined to <50% at 4 h. The addition of the specific inhibitor PD98059 completely abolished the activation of ERK and aggravated the extent of apoptosis. Moreover, propofol treatment repressed the mRNA expression of proapoptotic genes Bad and Bax, and this repression could be partly reversed by PD98059.
These findings demonstrate that propofol protects hepatic L02 cells from H2O2-induced apoptosis, partly through activating the MEK-ERK pathway and further suppressing Bad and Bax expression.
Anesthesia and analgesia 08/2008; 107(2):534-40. DOI:10.1213/ane.0b013e3181770be9 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Volatile anesthetics interfere with inflammatory cytokine production and expression of adhesion molecules which are critical for ischemia reperfusion induced injury. Nuclear factor (NF)-kappaB has been reported to be suppressed in this process, but the detailed molecular mechanism is still unclear.
In this study, ECV304 (a human umbilical vein endothelial cell line) was preconditioned with 30 min desflurane (1 minimal alveolar concentration), after 15 min washout, 30 min anoxia, and 60 min reoxygenation was performed. ECV304 was finally stimulated with tumor necrosis factor (TNF)-alpha (10 ng/mL). Control groups, which were not preconditioned and/or not stimulated, were also included in the protocol. IkappaB-alpha, phospho-IkappaB-alpha, phospho-IkappaB kinase (IKKalpha)/IKKbeta, and phospho-p38 were detected by Western blotting. The nuclear NF-kappaB p65 subunit was measured by subcellular fractionation and Western blotting. The surface expression of TNF-R1 was measured by flow cytometry. Receptor-associated signaling adaptors, e.g., TNF receptor-associated factor 2 (TRAF2) and IKK-alpha, were evaluated by immunoprecipitation by TNF-R1 antibody and subsequent Western blotting.
Desflurane preconditioning inhibits IkappaB-alpha phosphorylation, degradation, and p65 nuclear localization. Desflurane also affects p38 phosphorylation, which is needed for optimal inflammatory response. The phosphorylation of IKKalpha/IKKbeta was suppressed by preconditioning while the surface abundance of TNF-R1 was not affected. The association of TRAF2 and IKK-alpha with TNF-R1 was compromised by desflurane.
Our results suggest that the molecular target of desflurane in the NF-kappaB pathway is upstream of IKK activation. The abundance of TNF-R1 on the cell membrane is not affected by anesthetic preconditioning. We suggest that desflurane preconditioning targets the proximal end of TNF-alpha signaling.
Anesthesia and analgesia 06/2008; 106(5):1473-9, table of contents. DOI:10.1213/ane.0b013e318168b3f2 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Propofol has been demonstrated to ameliorate cerebral ischemic injury and attenuate changes in multiple links of molecular reaction included in the paths to apoptosis. The experiment was aimed to evaluate whether propofol neuroprotection was mediated through the ability to regulate pathologic time-course of apoptosis.
The effect of propofol given at a series of time points during ischemia-reperfusion period was determined using an intraluminal middle cerebral artery occlusion model in rats. The morphological changes of apoptosis under different duration of ischemia were detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin in situ nick labeling staining, and the effect of propofol on apoptosis was observed. The expression of anti-apoptotic protein bcl-2 in post-ischemia neurons and the influence of propofol was analyzed by immunochemistry staining.
Propofol attenuated neurological deficit, reduced infarct volumes, when given prior the onset of ischemia, during ischemia or 3 h after reperfusion. Apoptosis obviously appeared at 6 h post-reperfusion preceded by 90 min ischemia, rose to the maximum value at 24 h post-reperfusion and gradually diminished after 3 days reperfusion. Propofol inhibited apoptotic morphological changes between 6 h and 3 days post-reperfusion. Propofol enhanced the expression of anti-apoptotic protein bcl-2 in post-reperfusion neurons.
The pathologic outcome of focal cerebral ischemia-reperfusion injury was displayed by co-existence of apoptosis and necrosis. A short duration of ischemia induced apoptosis. The therapeutic window for propofol initiated before the onset of ischemia and lasted until early stage of reperfusion. The neuroprotection of propofol might be attributed to the inhibition of apoptosis.