Sevoflurane Pretreatment Research Articles

Sevoflurane prevents lipopolysaccharide-induced barrier dysfunction in human lung microvascular endothelial cells: Rho-mediated alterations of VE-cadherin

Acute lung injury (ALI) mainly occurs as increased permeability of lung tissue and pleural effusion. Inhaled anesthetic sevoflurane has been demonstrated to alleviate lung permeability by upregulating junction proteins after ischemia-reperfusion. However, the exact mechanisms of its protective effect on reperfusion injury remain elusive. The aim of this study was to assess possible preconditioning with sevoflurane in an in vitro model of lipopolysaccharide (LPS)-induced barrier dysfunction in human lung microvascular endothelial cells (HMVEC-Ls). In this study, HMVEC-Ls were exposed to minimum alveolar concentration of sevoflurane for 2 h. LPS significantly increased the permeability of HMVEC-L. Moreover, the distribution of junction protein, vascular endothelial (VE)-cadherin, in cell–cell junction area and the total expression in HMVEC-Ls were significantly decreased by LPS treatment. However, the abnormal distribution and decreased expression of VE-cadherin and hyperpermeability of HMVEC-Ls were significantly reversed by pretreatment with sevoflurane. Furthermore, LPS-induced activation of the RhoA/ROCK signaling pathway was significantly inhibited with sevoflurane. Such activation, abnormal distribution and decreased expression of VE-cadherin and hyperpermeability of HMVEC-Ls were significantly inhibited with sevoflurane pretreatment or knockdown of RhoA or ROCK-2. In conclusion, sevoflurane prevented LPS-induced rupture of HMVEC-L monolayers by suppressing the RhoA/ROCK-mediated VE-cadherin signaling pathway. Our results may explain, at least in part, some beneficial effects of sevoflurane on pulmonary dysfunction such as ischemia-reperfusion injury.

Role of the Toll‑like receptor3 signaling pathway in the neuroprotective effect of sevoflurane pre‑conditioning during cardiopulmonary bypass in rats.

The aim of the present study was to explore the roles and possible molecular mechanism of the alleviating effect of sevoflurane pre-treatment on the extracorporeal circulation and to investigate the possible involvement of the Toll-like receptor (TLR3) signaling pathway. A total of 64 male Sprague Dawley rats were randomly divided into three groups: The sham operation group (H group; n=8), cardiopulmonary bypass (CPB) group (C group; n=24) and sevoflurane pre-conditioning group (S group; n=32). The C group was subjected to tracheal intubation and mechanical ventilation, vessel puncture and catheter placement in the right femoral artery and right internal jugular vein, while no CPB was performed in the H group. The S group was pre-treated with 2.4% sevoflurane for 1 h prior to establishing the CPB model. The CPB in the C and S groups was performed for 1 h. Blood of the rats was analyzed and clinical parameters were detected prior to, during and at various time-points after CPB. In addition, eight rats from the C and S groups each were sacrificed at these time-points and brain tissue samples were analyzed. The levels of the brain damage-specific protein S100-β as well as IL-6 and IFN-β in the serum were detected by ELISA; furthermore, the expression levels of TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) in the left hippocampus were assessed by ELISA and/or western blot analysis. The right hippocampus was assessed for neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mean arterial pressure, heart rate and hematocrit were significantly decreased following CPB (P<0.05), while there was no significant changes in any other clinical parameters. The serum levels of S100-β and IL-6 in the C group were significantly increased compared with those in the H group (P<0.05), which was attenuated by sevoflurane-pre-treatment. Compared with the H group, the serum levels of IFN-β as well as hippocampal protein levels of TLR3 and TRIF were significantly increased in the C group during and after CPB (P<0.05), which was markedly aggravated in the S group (P<0.05). The number of apoptotic hippocampal neurons, although being generally low, was significantly increased in the C group compared with that in the H group (P<0.05), while apoptosis was significantly attenuated by sevoflurane-pre-treatment (P<0.05). The present study therefore concluded that 2.4% sevoflurane pre-treatment has a protective effect on the rat brain against CPB-induced injury, which may be mediated via the TLR3 signaling pathway through upregulating the expression levels of anti-inflammatory and downregulating pro-inflammatory proteins.

Effects of sevoflurane on tight junction protein expression and PKC-α translocation after pulmonary ischemia-reperfusion injury.

Pulmonary dysfunction caused by ischemia-reperfusion injury is the leading cause of mortality in lung transplantation. We aimed to investigate the effects of sevoflurane pretreatment on lung permeability, tight junction protein occludin and zona occludens 1 (ZO-1) expression, and translocation of protein kinase C (PKC)-α after ischemia–reperfusion. A lung ischemia-reperfusion injury model was established in 96 male Wistar rats following the modified Eppinger method. The rats were divided into four groups with 24 rats in each group: a control (group C), an ischemia-reperfusion group (IR group), a sevoflurane control group (sev-C group), and a sevoflurane ischemia-reperfusion group (sev–IR group). There were three time points in each group: ischemic occlusion for 45 min, reperfusion for 60 min and reperfusion for 120 min; and there were six rats per time point. For the 120-min reperfusion group, six extra rats underwent bronchoalveolar lavage. Mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at each time point. The wet/dry weight ratio and lung permeability index (LPI) were measured. Quantitative RT-PCR and Western blot were used to measure pulmonary occludin and ZO-1, and Western blot was used to measure cytosolic and membranous PKC-α in the lung. Lung permeability was significantly increased after ischemia–reperfusion. Sevoflurane pretreatment promoted pulmonary expression of occludin and ZO-1 after reperfusion and inhibited the translocation of PKC-α. In conclusion, sevoflurane pretreatment alleviated lung permeability by upregulating occludin and ZO-1 after ischemia–reperfusion. Sevoflurane pretreatment inhibited the translocation and activation of PKC-α, which also contributed to the lung-protective effect of sevoflurane.

Sevoflurane pretreatment attenuates TNF-α-induced human endothelial cell dysfunction through activating eNOS/NO pathway

Endothelial dysfunction induced by oxidative stress and inflammation plays a critical role in the pathogenesis of cardiovascular diseases. The anesthetic sevoflurane confers cytoprotective effects through its anti-inflammatory properties in various pathologies such as systemic inflammatory response syndrome and ischemic-reperfusion injury but mechanism is unclear. We hypothesized that sevoflurane can protect against tumor necrosis factor (TNF)-α-induced endothelial dysfunction through promoting the production of endothelium-dependent nitric oxide (NO). Primary cultured human umbilical vein endothelial cells (HUVECs) were pretreated with different concentrations (0.5, 1.5 and 2.5 minimum alveolar concentration, MAC) of sevoflurane for 30 min before TNF-α (10 ng/mL) stimulation for 4 h. Sevoflurane pretreatment significantly reduced TNF-α-induced VCAM-1, ICAM-1, IκBα, and NF-κB activation, and blocked leukocytes adhesion to HUVECs. Meanwhile, sevoflurane (1.5 and 2.5 MAC) significantly induced endothelial nitric oxide synthase (eNOS) phosphorylation and enhanced NO levels both intracellularly and in the cell culture medium. All these cytoprotective effects of sevoflurane were abrogated by NG-nitro-l-arginine methyl ester (l-NAME), a non-specific nitric oxide synthase inhibitor. Collectively, these data indicate that sevoflurane protects against TNF-α -induced vascular endothelium dysfunction through activation of eNOS/NO pathway and inhibition of NF-κB.

Sevoflurane protects against intestinal ischemia–reperfusion injury partly by phosphatidylinositol 3 kinases/Akt pathway in rats

Intestinal ischemia-reperfusion injury (IRI) is a clinical challenge with high morbidity and mortality, leading to intestine damage, systemic inflammation, and multiorgan failure. Previous research has shown that the inhaled anesthetic sevoflurane protects various organs from IRI. However, whether sevoflurane protects against intestinal IRI and which application condition is the most effective are not completely clear. Thus, we investigated the effects of sevoflurane on intestinal IRI with sevoflurane given before, during or after intestinal ischemia, and the role of phosphatidylinositol 3 kinases (PI3K)/Akt pathway in these effects. Rat model of intestinal ischemia-reperfusion (IR) was used in this study. The superior mesenteric artery was clamped for 60 minutes followed by 120 minutes of reperfusion. Sevoflurane at 0.25, 0.5, and 1.0 minimum alveolar concentration (MAC) was inhaled for 30 minutes before, during, or after ischemic insult. LY294002, a PI3K inhibitor, was injected intraperitoneally before sevoflurane inhalation. Intestinal IR caused a significant decrease of mean arterial blood pressure, severe intestinal mucosa injury and epithelial cell apoptosis, downregulation of the levels of phospho-Akt and phospho-Bad proteins. Exposure to 0.5 or 1.0 MAC sevoflurane before or after intestinal ischemia or 0.5 MAC during intestinal ischemia significantly ameliorated IR-induced histopathologic changes and decreased Chiu's scores. Pretreatment with 0.5 MAC sevoflurane also inhibited intestinal IR-induced increase of terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling-positive cells and activation of caspase-3 and restored expression of phospho-Akt and phospho-Bad. LY294002 partly blocked the protective effects induced by 0.5 MAC sevoflurane pretreatment. Our results suggest that sevoflurane inhalation at clinical related concentration before, during, or after ischemia protects against IR-induced intestinal injury. The pretreatment-induced protection was partly mediated by inhibiting intestinal mucosal epithelial apoptosis via activation of the PI3K/Akt pathway.

Sevoflurane downregulates interleukin-6 and interleukin-8 levels in patients after cardiopulmonary bypass surgery: a meta-analysis.

This study aimed to investigate the effect of sevoflurane on serum levels of interleukin (IL)-6 and IL-8 in patients who underwent cardiopulmonary bypass (CPB). The strength of the association between sevoflurane treatment and serum level of IL-6 and IL-8 was determined in patients who underwent CPB by summary standard mean differences (SMDs); 95% confidence interval (CI) was used. In total, seven case-control studies showed decreased IL-6 and IL-8 levels in sevoflurane-treated patients than in controls (IL-6: SMD = 1.56, 95%CI: 0.95-2.17, P < 0.001; IL-8: SMD = 1.63, 95%CI: 0.30-2.96, P < 0.001, respectively). Further, IL-6 and IL-8 levels were significantly higher in sevoflurane-treated patients than in sevoflurane-pretreated patients (IL-6 post vs pre: SMD = 2.17, 95%CI: 1.40-2.95, P < 0.001; IL-8 post vs pre: SMD = 4.01, 95%CI: 2.80-5.21, P < 0.001, respectively). CPB-stratified analysis showed significant decrease in IL-6 and IL-8 levels in sevoflurane-treated patients than in controls, irrespective of the time after CPB surgery (P < 0.05). Moreover, sevoflurane-pretreated patients under the <12-h subgroup showed decreased IL-6 levels (P = 0.698), while all other subgroups showed decreased IL-8 levels (P < 0.05). Further, subgroup analysis by different dose of sevoflurane showed decreased IL-6 and IL-8 levels in subgroups administered with a dose of <2 and ≥ 2% sevoflurane under the case vs control and pre- vs post-treatment of sevoflurane models. Serum IL-6 and IL-8 levels were significantly lower in sevoflurane-treated patients who underwent CPB, suggesting sevoflurane pretreatment to be more beneficial than post-treatment.

Effects of sevoflurane pretreatment on expression of interleukin-17 in rats with lipopolysaccharide-induced acute lung injury

Objective To evaluate the effects of sevoflurane pretreatment on the expression of interleukin-17 (IL-17) in rats with lipopolysaccharide (LPS)-induced acute lung injury.Methods Thirty-two adult male Sprague-Dawley rats,weighing 220-260 g,aged 2 months,were randomly divided into 4 groups (n =8 each):control group (group C),sevoflurane group (group S),LPS group (group L) and sevoflurane + LPS group (group SL).ALI was induced by slow intra-tracheal instillation of LPS 5 mg/kg in L and SL groups,while the equal volume of normal saline was administered in the same way in the other two groups.The rats inhaled 2.4 ％ sevoflurane for 30 min,and then normal saline and LPS were given in S and SL groups,respectively.The rats were sacrificed at 12 h after administration of LPS.The left main bronchus was lavaged and broncho-alveolar lavage fluid (BALF) was collected for determination of white blood cell (WBC) and polymorphonuclear leukocyte (PMN) counts.The right lung was removed for microscopic examination by using light microscope and for determination of -L-17 mRNA and protein expression in the right lung tissues.Results Compared with group C,WBC and PMN counts were significantly increased,and IL-17 mRNA and protein expression was up-regulated in L and SL groups.Compared with group L,WBC and PMN counts were significantly decreased,and IL-17 mRNA and protein expression was down-regulated in group SL.The pathological changes of lungs were significantly mitigated in group SL as compared with group L.Conclusion Sevoflurane pretreatment can reduce inflammatory reponses in rats with LPS-induced acute lung injury,and down-regulation of IL-17 expression in lung tissues is involved in the mechanism. Key words: Anesthetics, inhalation ; Respiratory distress syndrome, adult; Endotoxemia; Interleukin-17

Effect of sevoflurane pretreatment on inflammatory response during renal ischemia-reperfusion in rats

Objective To evaluate the effect of sevoflurane pretreatment on the inflammatory response during renal ischemia-reperfusion (I/R) in rats.Methods Thirty pathogen-free male Sprague-Dawley rats,aged 12-14 weeks,weighing 220-260 g,were randomized into 3 groups (n =10 each) using a random number table:sham operation group (group S),I/R group and sevoflurane pretreatment group (group SP).Renal I/R was induced by clamping the left renal pedicle for 45 min followed by reperfusion in I/R and SP groups.In group S inhalation of 3％ sevoflurane in O2 was started at 30 min before I/R and maintained throughout the experiment.Venous blood samples were taken at 3 h of reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The animals were then sacrificed and the left kidneys were removed for microscopic examination and for measurement of the content of tumor necrosis factor-apha (TNF-α),interleukin-6 (IL-6) and intercellular cell adhesion molecule-1 (ICAM-1) in renal tissues (by ELISA).Results Compared with group S,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules (0 =normal,4 =necrosis of whole segment of proximal convoluted tubules),and contents of TNF-α,IL-6 and ICAM-1 were significantly increased in I/R and SP groups (P ＜ 0.05).Compared with group I/R,the serum BUN and Cr concentrations,severity of necrosis of renal proximal convoluted tubules,and contents of TNF-α,IL-6 and ICAM-1 were significantly decreased in SP group (P ＜ 0.05).Conclusion Sevoflurane pretreatment can protect kidney against I/R injury by inhibiting the inflammatory responses in the renal tissues of rats. Key words: Anesthetics, inhalation ; Reperfusion injury; Kidney ; Inflammation

Protective effect of sevoflurane on hepatic ischaemia/reperfusion injury in the rat

Ischaemia/reperfusion injury is a common problem in hepatic surgery. An appreciation of the role of sevoflurane dose in preconditioning and subsequent hepatoprotection against ischaemia/reperfusion injury would be useful. The aim of current study was to investigate the protective effect of sevoflurane preconditioning at different doses on hepatic ischaemia/reperfusion injury in rats. Randomised, controlled, laboratory study. The Department of Anaesthesiology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, China. Fifty male Sprague-Dawley rats weighing 200 to 250 g, randomly assigned to five groups. Control group (sham surgery, no ischaemia/reperfusion), I/R group (ischaemia/reperfusion but no sevoflurane pretreatment), S1 [1 minimum alveolar concentration (MAC) = 2.4%], S2 (1.5 MAC = 3.6%) and S3 (2 MAC = 4.8%) groups with sevoflurane pretreatment, respectively, followed by 60 min ischaemia and 120 min reperfusion. At the end of reperfusion, serum levels of alanine aminotransferase and aspartate aminotransferase as well as superoxide dismutase activity, myeloperoxidase and malondialdehyde content in the liver were determined. Histological examination of the liver was also performed. Serum levels of aspartate aminotransferase and alanine aminotransferase in the sevoflurane groups were significantly reduced compared to the elevated levels seen in the I/R group (P < 0.05). In the liver, the I/R-induced increase in myeloperoxidase activity and malondialdehyde level were significantly reduced by all sevoflurane concentrations (P < 0.05). The decrease in superoxide dismutase activity induced by I/R was prevented by all sevoflurane pretreatments (P < 0.05). No significant differences between the S1, S2 and S3 groups were seen in any of the above variables. Sevoflurane pretreatment exerts a protective effect on hepatic ischaemia/reperfusion injury but there is no significant dose-response relationship in the concentration range used. It is possible that a dose-response relationship might exist at lower concentrations.

The role of protein kinase C and mito ATP-sensetive potassium channel in sevoflurane preconditioning against intestinal ischemia/reperfusion injury in rats

Objective To investigate the role of protein kinase C (PKC) and mito ATP-sensetive potassium channel(mKATP) channels in 0.5 MAC sevoflurane (1.15％) pretreatment preventing intestinal ischemia/reperfusion injury(Ⅰ/RI)in rats.Methods 45rats were randomly divided into five groups (n=9):① Sham-operated group (Sham group); ② The intestinal ischemia/reperfusion group (Ⅱ/R group); ③ 0.5 MAC sevoflurane preconditioning group (APC group); ④ PKC nonspecific blocker Chelerythrine group (CHE group):intraperitoneal injection of CHE 5 mg/kg at 15 min before 0.5 MAC sevoflurane pretreatment; ⑤ mKATP channel blocker 5-Hydroxydecanoic group (5HD group):intraperitoneal injection of 5HD 10 mg/kg at 15 min before 0.5 MAC sevoflurane pretreatment.Three pieces of intestinal tissues were used as following at 120 min after reperfusion:the pathological changes of intestinal tissues structure were observed by HE staining tissue sections and scored by improved Chiu's in the microscope.The expression of cysteinyl aspartate specific proteinase-3 (Caspase-3) was observed by immunohistochemistry.The expressions of B cell lymphoma/lewkmia-2 (Bcl-2) and Caspase-3 in intestinal tissues were detected by Western blotting.Results Chiu's pathological score in APC group (4.0±1.3) was significantly lower than that of Ⅱ/R group (6.7±1.1),CHE (6.8±1.1) and 5HD group (5.8±1.2) (P＜0.01).The latter three groups showed no significant difference (P＞0.05).Compared with sham group,Bcl-2 and Caspase-3expression levels in the other four groups increased significantly (P＜0.01).Compared with APC group,Bcl-2 expression levels in CHE group,5HD group and Ⅱ/R group decreased significantly(P＜0.05).Compared with sham group,Caspase-3 expression levels in the other four groups increased significantly (P＜0.01).The increased level of APC group is significantly less than CHE group,the 5HD group Ⅱ/R group (P＜0.01),the latter three groups showed no significant difference (P＞0.05).Conclusions 0.5 MAC sevoflurane pretreatment could protect against the intestinal Ⅱ/R through activation of PKC and mKATP channel. Key words: Reperfusion injury; Intestines; Sevoflurane; Preconditioning; Protein kinase C ; Mito ATP-sensetive potassium channel

Effects of sevoflurane pretreatment on renal Src and FAK expression in diabetic rats after renal ischemia/reperfusion injury

The diabetic kidney is sensitive to ischemia-reperfusion (I/R) injury due to microvascular complications, such as cellular apoptosis and necrosis. The aim of this study was to determine if sevoflurane pretreatment could help preserve renal function in rats with diabetes mellitus (DM) by altering non-receptor tyrosine kinases steroid receptor coactivator (Src) and focal adhesion kinase (FAK) expression (Src and FAK are mediators of cellular apoptosis and necrosis). Male rats (N=40) were randomly assigned to one of five groups: Group A, sham operation; Group B, renal I/R injury; Group C, DM+sham operation; Group D, DM+renal I/R injury; and Group E, DM+sevoflurane pretreatment+renal I/R injury. Sevoflurane pretreatment comprised exposure to 2.5% sevoflurane for 30min, followed by exposure to air for 10min. After 24h, serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal Src and FAK expression (immunohistochemistry) were assessed. Compared with rats in C, rats in D had significantly higher Cr and BUN levels, but significantly lower renal Src and FAK expression. Rats in E had significantly lower serum Cr and BUN levels and significantly higher renal Src and FAK expression levels than rats in D. Our findings suggest that sevoflurane pretreatment in rats with DM protects the kidneys from ischemia/reperfusion injury in part due to increased renal Src and FAK expression.

Sevoflurane and Isoflurane Preconditioning Provides Neuroprotection by Inhibition of Apoptosis-related mRNA Expression in a Rat Model of Focal Cerebral Ischemia

This study aimed to examine the effects of sevoflurane or isoflurane preconditioning on cerebral ischemia/reperfusion-induced inflammation, oxidative stress, and lipid peroxidation and test the hypothesis that the underlining mechanism of the protective effect of preconditioning involves changes in the apoptotic gene expression profiles in an experimental model of middle cerebral artery occlusion in rats. Twenty-four adult male rats were randomly divided into 3 groups: control (n=8), sevoflurane (n=8), and isoflurane (n=8). For preconditioning, these 3 groups were exposed to 40% O2, 2% sevoflurane, and 1.5% isoflurane, respectively, for 60 minutes, followed immediately by 1 hour of middle cerebral artery occlusion and then 6 hours of reperfusion. Blood and brain tissue samples were collected for determination of blood gas tension, tumor necrosis factor-α, interleukin-6, and interleukin-1β. Brain tissue samples were collected for determination of the wet/dry ratio, myeloperoxidase, malondialdehyde, and total RNA and also for histologic examinations. Tumor necrosis factor-α, interleukin-1β, and myeloperoxidase levels decreased and antioxidant enzyme levels increased in the sevoflurane group compared with the control and isoflurane groups. Proapoptotic genes (Tnf, Tnfrsf10b, and Tp53) downregulated and antiapoptotic genes (Aven, Bcl2, Bcl2l2, and Prok2) upregulated with sevoflurane treatment compared with the isoflurane and control groups. Both isoflurane and sevoflurane pretreatment decreased malondialdehyde, Dffb, the wet/dry ratio, and injury score and upregulated Bax and Apaf 1 compared with the control group. Sevoflurane and isoflurane preconditioning ameliorates inflammation, cerebral lipid peroxidation, and histologic injury. Downregulation of proapoptotic molecules and upregulation of antiapoptotic molecules may be associated with this effect.

Effects of sevoflurane pretreatment on inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To investigate the effects of sevoflurane pretreatment on the inflammatory response in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB) and the mechanism of myocardial protection.Methods Twenty NYHA class Ⅱ or Ⅲ patients of both sexes,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n=10 each): sevoflurane group (group S) and control group (group C).The patients were premedicated with intramuscular morphine 0.1 mg/kg and scopolamine 0.3 mg.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.The patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with intermittent iv boluses of midazolam0.03-0.06 mg/kg,fentanyl 5-10μg/kg and pipecuronium 0.04-0.08 mg/kg.Sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly adjusted to 1.0％ and maintained at this level for 30 min in group S.Blood samples were taken from the central vein before skin incision,immediately after aortic clamping,immediately after aortic unclamping and at 30 min after aortic unclamping,at 2,6,12 and 24 h (T1-8) after operation for determination of the concentrations of plasma tumor necrosis factor-α (TNF-α),interleukin-6 (IL) and interleukin-8 (IL-8),intercellular adhesion molecule-1 (ICAM-1),cardiac troponin I (cTnI) and activity of creatine kinase MB (CK-MB).The requirement for cardiovascular drugs was recorded after release of aortic cross clamp.Results Compared with group C,the plasma concentrations of TNF-α,IL-6 and IL-8 were significantly decreased at T3-8,the plasma concentrations of ICAM-1 and cTnl were significantly decreased at T4-8,the activity of plasma CK-MB was significantly decreased at T8,and the requirement for cardiovascular drugs was significantly reduced after release of aortic cross clamp in group S (P ＜0.05).Conclusion Sevoflurane pretreatment can inhibit the inflammatory response and provide myocardial protection to some extent in patients undergoing cardiac valve replacement with CPB. Key words: Anesthetics,inhalation; Cardiopulmonary bypass; Myocardial; Inflammation

Effects of sevoflurane pretreatment on myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To investigate the effects of sevoflurane pretreatment on the myocardial injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Twenty NYHA class Ⅱ or Ⅲ patients,aged ＜ 60 yr,undergoing cardiac valve replacement with CPB,were randomly divided into 2 groups (n =10 each):sevoflurane group (group S) and control group (group C).The patients were premeditated with intramuscular morphine and scopolamine.Anesthesia was induced with iv injection of midazolam 0.05-0.08 mg/kg,fentanyl 10-15 μg/kg and pipecuronium 0.08-0.10 mg/kg.Anesthesia was maintained with intermittent iv boluses of midazolam,fentanyl and pipecuronium and in addition sevoflurane was inhaled before aortic clamping and the end-tidal concentration was rapidly increased to 1.0％ and maintained at the level for 5 min in group S.Blood samples were taken from the central vein before skin incision (T1),immediately after aortic clamping (T2 ),at 0 and 30 min after aortic unclamping (T3-4),and at 2,6,12 and 24 h after operation (T5-8) for determination of the concentration of serum cardiac troponin Ⅰ (cTnI) and activities of creatine kinase (CK) and creatine kinase isoenzyme-MB (CK-MB).Myocardial specimens were taken from right auricle before aortic clamping and at 10 min after aortic unclamping for electron microscopic examination.Results The concentration of serum cTnI and activities of CK and CK-MB were significantly increased at T4-8 in both groups ( P ＜ 0.05).The serum cTnI concentration at T4-8 and the activities of CK and CK-MB at T8 were significantly lower in group S than in group C ( P ＜0.05).Different degrees of mitochondrial swelling were observed after aortic unclamping in both groups,but the changes were milder in group S than in group C.Conclusion Sevoflurane pretreatment can attenuate the myocardial injury in patients undergoing cardiac valve replacement with CPB. Key words: Anesthetics, inhalation; Cardiopulmonary bypsss; Myocardial reperfusion injury; Heart valve prosthesis implantation

English

To observe the effect of sevoflurane pretreatment with different concentrations on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and expression of heme oxygenase-1 (HO-1). Sprague-Dawley (SD) rats were divided into six groups in different sevoflurane pretreatment experiment, Group A (control), Group B (1.5 MAC sevoflurane), Group C (1.5 MAC sevoflurane + LPS), Group D (1.0 MAC sevoflurane + LPS), Group E (0.5 MAC sevoflurane + LPS) and Group F (LPS) at random. Besides, SD rats were divided into other six groups in induced HO-1 expression experiment, Group A (control group), Group B (ZnPP), Group C (1.0 MAC sevoflurane), Group D (1.0 MAC sevoflurane + LPS), Group E (ZnPP + 1.0 MAC sevoflurane + LPS) and Group F (LPS). Using traditional method to detect pathological changes, wet/dry ratio (W/D), myeloperoxidase (MPO) and HO-1 activity; detecting the mRNA and protein level of cytokine-induced neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1(ICAM-1) and HO-1 by&nbsp;RT-PCR and Western blot. 1.0 MAC sevoflurane pre-treatment could effectively protect ALI with decreasing pathomorphological scores, MPO activity, W/D and down-regulated expression of ICAM-1 and CINC. Furthermore, 1.0 MAC sevoflurane pre-treatment could significantly induced HO-1 expression suggesting sevoflurane may protect ALI from inflammation through inducing abundant HO-1 expression. Sevoflurane pre-treatment may be an effective avenue to alleviate ALI through inducing HO-1 expression. &nbsp; Key words:&nbsp;Sevoflurane, acute lung injury, heme oxygenase-1 (HO-1).

Effect of sevoflurane pretreatment on renal ischemia-reperfusion-induced apoptosis in kidney in rats

Objective To investigate the effects of sevoflurane pretreatment on renal ischemia-reperfusion (I/R)-induced apoptosis in kidney in rats. Methods Thirty pathogen-free male SD rats weighing 220-260 g were randomized into 3 groups (n=10 each):group control (group C);group I/R and group sevoflurane(group S). Renal I/R was induced by clamping the left renal pedicle for 45 min in I/R and S groups. In group S inhalation of 2.2% sevoflurane in O2 was started at 30 min before operation and maintained throughout the experiment.Venous blood samples were taken at 3 h of reperfusion for determination of serum BUN and Cr concentrations. The animals were then sacrificed and the left kidneys were removed for microscopic examination, detection of apoptosis(by TUNEL)and determination of heme oxygenase-1(HO-1) mRNA and protein expression (by RT-PCR and Western blot).Results Renal I/R significantly increased serum BUN and Cr concentrations, apoptotic index(percentage of apoptotic cells) and the severity of necrosis of renal proximal convoluted tubules (0=normal,4=necrosis of whole segment of proximal convoluted tubules).Sevoflurane inhalation attenuated the I/R-induced changes mentioned above.HO-1 mRNA and protein expression was up-regulated by I/R and HO-1 mRNA expression was further up-regulated by sevoflurane inhalation.Conclusion Sevoflurane pretreatment can protect kidney against I/R injury by attenuating cell apoptosis.Up-regulation of HO-1 mRNA expression may be involved in the mechanism. Key words: Reperfusion injury; Kidney; Apoptosis; Sevoflurane

Sevoflurane preconditioning protects blood-brain-barrier against brain ischemia

Sevoflurane preconditioning has recently been demonstrated to protect ischemic brain in vivo and in vitro. However, mechanisms underlying this neuroprotection have not been delineated. We therefore assessed the hypothesis that sevoflurane pretreatment protected blood-brain-barrier (BBB) via suppression of cell adhesion molecules (CAMs) and matrix metalloproteinases (MMPs) after ischemia. Repeated sevoflurane preconditioning was administered 24 hours before transient middle cerebral artery occlusion (MCAO). Neurologic deficits and expression of CAMs, MMPs and occludin were examined up to 3 days after ischemia. Evans blue (EB) extravasation and electron microscopy was detected at 2 days after ischemia. The data showed that sevoflurane pretreatment markedly improved BBB integrity and neurological outcomes after ischemia, robustly suppressed ischemia-induced decreases of occludin and increases of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), MMP-2, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1). Sevoflurane pretreatment also suppressed the activation of astrocytes and microglias in ipsilateral cortex and corpus callosum. In conclusion, repeated sevoflurane preconditioning confered potent protection against brain ischemia, partly by improving BBB integrity.

Effect of different concentrations of sevoflurane pretreatment on acute lung injury induced by endotoxin in rats.

To investigate the effect of 3 concentrations of sevoflurane pretreatment on acute lung injury induced by endotoxin in rats. Thirty-six male SD rats were randomly divided into 6 groups:a control group(Group A), a sevoflurane group(Group B), a 3.6% sevoflurane pretreatment group(Group C), a 2.4% Sevoflurane pretreatment group(Group D), a 1.2% sevo sevoflurane pretreatment group(Group E), and lipopolysaccharide (Group F).The rats were killed 6 h after lipopolysaccharide (LPS) or saline injection.Histological examinations of the lung tissues were performed with light microscope. Lung wet/dry weight (W/D) ratio, myeloperoxidase (MPO) activity, and intercellular adhesion molecule-1 (ICAM-1) mRNA expression were assayed. Introvenous LPS significantly aggravated lung tissue damage,increased lung W/D ratio, MPO activity, and lung ICAM-1 mRNA expression compared with the control group(P<0.05). Precondition with 2.4% sevoflurane significantly attenuated the above-mentioned changes induced by LPS (P<0.05). The 3.6% LPS (Group C) significantly attenuated lung tissue damage and decreased MPO activity,lung ICAM-1 mRNA expression compared with the Group F (P<0.05),but no significant change in lung W/D ratio was seen (P>0.05). MPO activity was significantly decreased in Group E (P<0.05), but lung W/D ratio and lung ICAM-1 mRNA expression had no significant changes (P>0.05). Precondition with 2.4% sevoflurane can reduce LPS-induced lung injury in rats. Decreased expression of ICAM-1 and less accumulation of neutrophils were participated in its mechanism.

Protective effects ofsevoflurane pretreatment on LPS-induced acute lung injury in rats

：Objective To investigatethe effects of sevoflurane pretreatment on Lipopolysaccharide (LPS)-induced acute lunginjury (ALI) in rats. Methods Seventy -two Sprague -Dawley rats were randomly divided into6 groups: NS group, LPS group and sevoflurane pretreatment (S-l h group, S-6 h group, S-12h group and S-24 h group). The rat model of ALI was established by intratrachealinstillation of LPS. Animals were sacrificed at 6 h after LPS or NS administration.Leukocyte count, concentration of TNF-αand IL-β in bronchoalveolar lavage fluid (BALF); pulmonary capillarypermeability, myeloperoxidase (MPO) activity of lung tissue; lung histological changeswere compared in rats with or without sevoflurane pretreatment (2.4% inspired for 30 min)at different times before LPS instillation. Results Compared with the NS group,severeinjury of lung tissues and increase in leukocyte count in BALF, Production of TNF-α and IL-1β in BALF, pulmonary capillarypermeability and MPO activity in the lung were significantly increased in rats treatedwith LPS (P<0.01). MPO activity, leukocyte count and production of IL-1βinBALF were reduced when sevoflurane was given 1 or 24 h before but not at 6 or 12 h beforeLPS instillation(P<0.01). Sevoflurane pretreatment also attenuated pulmonary capillarypermeability and production of TNF-α in BALF (P<0.01).Pulmonary capillary permeability and concentration of TNF-α in S-l h and S-24 h group was lower than S-6 h and S-12 hgroup (P<0.01). Sevoflurane pretreatment was effective at 1 h and 24 h suggestingsevoflurane has early and late protection against LPS-induced lung injury. ConclusionSevoflurane pretreatment has protective effects against acute lung injury when given 1 or12 h before LPS instillation. Key words: Acute lunginjury; Sevoflurane; Lipopolysaccharides; Cytokines

Effect of sevoflurane pretreatment on expression of tight junction protein in the lung following ischemiareperfusion injury in rats

Objective To investigate the effect of sevoflurane pretreatment on the expression of tight junction protein Occludin and ZO-1 in the lung following ischemia-reperfusion (I/R) injury in rats. Methods Ninty-six adult male Wistar rats weighing 250-350 g were randomly divided into 4 groups ( n = 24 each): group Ⅰ sham operation (group S);group Ⅱ I/R; group Ⅲ sevoflurane (group Sevo) and group Ⅳ Sevo + I/R. The animals were anesthetized, tracheostomized and mechanically ventilated. Right femoral vein and left carotid artery were cannulated for BP monitoring, blood sampling and drug and fluid administration. Lung I/R was induced by clamping left pulmonary hilum for 45 min followed by 120 min reperfusion in group Ⅱ and Ⅳ. In group Ⅲ the animals inhaled 2.2 % sevoflurane for 30 min. In group Ⅳ the animals inhaled 2.2 % sevoflurane for 30 min before lung ischemia. Six animals were killed at the end of 45 min ischemia (T1), and 60 and 120 min of reperfusion (T2, T3 ). The lungs were immediately removed for determination of W/D lung weight ratio and the expression of Occludin and ZO-1 protein (by Western blot). Tissues of lung were obtained for observation of histopathology with light microscope. Lung permeability index (LPI) was calculated. Another 6 animals were killed at 120 min of reperfusion for lung lavage. Results I/R significantly increased W/D ratio and LPI and significantly reduced Occludin and ZO-1 protein expression in the lung tissue as compared with group C and Sev. Sevoflurane pretreatment significantly attenuated the I/R-induced changes. The pathological damage to the lung tissue was significantly less in group SP than in I/R. Conclusion Sevoflurane pretreatment may protect the lungs from I/R injury by up-regulating the expression of Occludin and ZO-1. Key words: Anesthetics,inhalation; Reperfusion injury; Lung; Tight junctions