Objective To investigate the effect of ondansetron on the analgesic efficacy of tramadol for postoperative patient-controlled intravenous analgesia (PCIA). Methods Forty ASA I - II patients aged 22-74 years, weighing 40-90 kg scheduled for radical mastectomy were randomly allocated to one of two groups : control group ( n = 20) and ondansetron group ( n = 20) . The patients were premedicated with intramuscular atropine 0.01 mg?kg-1 and diazepam 0.2 mg?kg-1. Anesthesia was induced with midazolam 0.1-0.2 mg (total dose was limited to 15 mg), fentanyl 2.4?g?kg-1 , propofol 1.5-2.0 mg?kg-1 and vecuronium 0.12-0.15 mg?kg-1 . The patients were mechanically ventilated after tracheal intubation (VT 8-10 ml?kg-1 , RR 13 bpm). Anesthesia was maintained with enflurane inhalation and continuous infusion of vecuronium. The patients were attached to a PCIA pump after operation and received PCIA with 1 % tramadol (background infusion 2 ml?h-1 , bolus dose 2 ml, lockout interval 10min) in both groups. In ondansetron group the patients received ondansetron 6 mg iv during operation and a loading dose of tramadol 1 mg?kg-1 and ondansetron 2 mg after operation before PCIA. Pain score (VAS 0-10), sedation score (0-3), tramadol consumption and the incidence of nausea and vomiting were recorded at 4, 8, 12 and 24 h after operation. Results There was no significant difference in pain and sedation scores and the incidence of vomiting between the two groups. Significantly more tramadol was consumed at 4, 8 and 12 h after operation in the ondansetron group as compared with control group (P

Objective To evaluate the efficacy of nalmefene in preventing sufentanil-induced cough during induction of general anesthesia.Methods One hundred American Society of Anesthesiologists physical status Ⅰ orⅡ patients of both sexes,aged 21-62 yr,weighing 45-82 kg,undergoing elective laparoscopic cholecystectomy under general anesthesia,were divided into 2 groups (n =50 each) using a random number table:nalmefene group (group N) and control group (group C).Nalmefene 0.25 μg/kg was injected intravenously at 2 min before anesthesia induction in group N,and the equal volume of normal saline was given instead in group C.Anesthesia was induced with target-controlled infusion of propofol,and sufentanil 0.5 μg/kg was injected over 5 s when bispectral index value reached 55.The number of patients who developed cough within 2 min after sufentanil injection and severity of cough were observed.Other iv anesthetics were given for induction after the end of observation.Results The incidence of sufentanil-induced cough was 8％ in group N and 48％ in group C.Compared with group C,the incidence and severity of cough were significantly decreased in group N (P＜0.05).Conclusion Nalmefene 0.25 μg/kg injected at 2 min before induction of anesthesia can effectively decrease the development of sufentanil-induced cough during induction of general anesthesia.

Objective To investigate the effect of Shenfu injection (SFI) on hypoxia and reoxygenation (H/R)-induced apoptosis and the expression of Bcl-2 and Caspase-3 in cultured neonatal rat cardiomyocytes and to explore the possible molecular protective mechanisms of SFI from hypoxia and reoxygenation injury in cardiacmy-ocytes in vitro. Method The experiment was performed in Research Center for Cardiovascular Regenerative Medicine, Cardiovascular Institute and Fuwai Hospital in Beijing. Ventricular myocytes from the hearts of neonatal Sprague-Dawley rats (1- to 2-day old) were cultured. The model of hypoxia and reoxygenation injury was devel-oped in primary cultured neonatal rat cardiacmyocytes. The cultured cells were randomly divided into four groups: (1) Control group (Con group), without any treatment; (2) Hypoxia and Reoxygenation group (H/R group),4 h hypoxia followed by 16 h reoxygenation; (3) Low-dose SFI group (L-SFI group),cardiacmyocytes were pretreated with a low dose (50 μL/mL) of SFI for 30 min followed by H/R; (4) High-dose SFI group (H-SFI group),car-diacmyocytes were pretreated with a high dose (100 μL/mL) of SFI for 30 min followed by H/R. Apoptosis was quantified by fluoreacence-activated cell sorter (FACS) analysis after staining with Fluorescein isothiocyanate (FITC)-labled Annexin-V (Annexin V-FITC) and propidine iodide (PI). The expressions of Bcl-2 and Caspase-3 were detected by ECL-Western blot analysis. All data are expressed as mean±S.E.M. One-way analysis of vari-ance (ANOVA) was performed followed by Student-Newman-Keul test using SSPS 11.5 software. A p value less than 0.05 were considered as statistically significant. Results The results of FACS analysis indicated that the rate of different apoptotic process in cardiomyocytes was significantly increased after H/R, while after SFI treatment the occurrence of cell apoptosis induced by H/R was decreased significantly. The results of ECL-Western blot analysis showed that cells' exposure to H/R induced proteolytic cleavage of caspases,as revealed by the appearance of the characteristic fragment at 17 000 of Caspase-3 and this proteolytic activation was nearly completed with difference concentration SFI incubation. The anti-apoptotic protein Bcl-2 in cardiomyocytes was decreased after H/R insult and was increased in cells with SFI pretreatment. Conclusions SFI has protective effects on cardiacmyocytes a-gainst apoptosis that could be induced by H/R injury, the mechanisms of which probably involve the inhibition of down-regulation of Bcl-2 protein level and sequential activation of Caspase-3.

ObjectiveTo compare the roles of Toll-like receptor-4 (TLR-4) in the acute lung injury (ALI) induced by lipopolysaccharide (LPS) and by hemorrhagic shock and resuscitation (HSR) and LPS (twohit) in mice.MethodsTwo types of mice were used in this study:free wild type mice (C3H/HeN) and TLR4 gene mutation type ( C3H/HeJ).Each type of mice was randomly divided into 2 groups ( n ＝ 18):group sham operation+ LPS (group S/LPS) and group HSR + LPS (group HSR/LPS).Hemorrhagic shock was induced by blood withdrawal until MAP was reduced to 35-45 ram Hg and maintained for 60 min (first hit).The animals were then resuscitated by infusion of shed blood and lactated Ringer' s solution.LPS 30 tμg/kg was instilled into trachea at 24 h after HSR (second hit).Arterial blood gas analysis was performed and the animals were then sacrificed by exsanguination at 0,3 and 6 h after LPS(T,,T2,T3 ).The lungs were removed.W/D lung weight ratio and MPO activity,IL-6 and 1L-10 contents in the lung tissue were determined.The changing rate of the abovementioned variables at T2,T3 based on the values at T1 were calculated.ResultsIn C3H/HeN animals the changing rate of PaO2 was significantly lower while the changing rate of W/D ratio,MPO activity and IL-6,IL-10 contents in the lung tissue were significantly higher in HSR/LPS group than in S/LPS group at T2.3.But in C3H/HeJ animals the above-mentioned variables were changed at T2.ConclusionThe role of TLR-4 in the two-hit-induced ALI is stronger than that in the LPS-induced ALI in mice.

ObjectiveTo investigate the effect of flurbiprofen axetil on lung ischemia-reperfusion(I/R) injury in rats.MethodsSixty healthy male SD rats weighing 250-300 g were randomly divided into 3 groups( n =20 each): group sham operation(group S) ;group I/R and group flurbiprofen axetil (group FA).The animals were anesthetized with intraperitoneal 2％ pentobarbital 50 mg/kg and tracheostomized and mechanically ventilated.Lung I/R was induced by 60 min occlusion of left hilus pulmonis followed by 120 min reperfusion.In FA group flurbiprofen axetil 10 mg/kg was injected iv at 15 min before occlusion of left hilus pulmonis.The rats were sacrificed at 120 min of reperfusion and then the lungs were removed for measurement of lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and microscopic examination.Bcl-2/Bax ratio was caculated.ResultsI/R significantly increased lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and decreased Bcl-2/Bax ratio.Flurbiprofen axetil preconditioning significantly attenuated the I/R-induced changes in lung wet/dry weight ratio,apoptosis index,NF-κB activity,Bcl-2 and Bax protien expression,and Bcl-2/Bax ratio in group FA as compared with group I/R.Flurbiprofen axetil preconditioning also ameliorated I/R-induced lung damage.ConclusionFlurbiprofen axetil can attenuate lung I/R injury in rats by inhibiting NF-κB activity,up-regulating Bcl-2 expression and down-regulating Bax expression and inhibiting apoptosis.

Objective To evaluate the role of Phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K/Akt) signaling pathway in reduction of hypoxia-reoxygenation (H/R)-induced injury to cardiomyocytes by propofol postconditioning in rats.Methods Primary cardiomyocytes were obtained from neonatal rats aged 1-3 days and cultured in DMEM culture medium.The cells were seeded in 96-well plates (density 1 × 105/ml,200 μl/well) or 6-well plates (density 5 × 105/ml,2 ml/well) and randomly assigned into 4 groups (n =24 each):control group (C group),H/R group,H/R + propofol group (H/R + P group) and H/R + propofol + wortmannin (a specific PI3K inhibitor) group (H/R + P + W group).The cells were routinely cultured for 6 h in group C.The cells were exposed to 2 h hypoxia followed by 4 h reoxygenation.Propofol with the final concentration of 50 μmol/L was added to the culture medium at the end of hypoxia in group H/R + P.Wortmannin (final concentration 100 nmol/L) and propofol (final concentration 50 μmol/L) was added to the culture medium at the end of hypoxia in group H/R + P + W.At the end of reoxygenation,the cell viability was measured by MTT assay,the lactic dehydrogenase (LDH) activity was detected in the culture medium,the cell apoptosis was assessed by flow cytometry,and the expression of phosphorylated Akt (p-Akt),Bcl-2 and Bax in cardiomyocytes were determined by Western blot.The apoptotic rate and Bcl-2/Bax ratio were calculated.Results Compared with C group,the cellviability was significantly decreased,the LDH activity and apoptotic rate were increased,p-Akt and Bax expression was up-regulated and Bcl-2 expression was down-regulated in H/R group (P ＜ 0.05).Compared with H/R group,the cell viability and Bcl-2/Bax ratio were significantly increased,the LDH activity and apoptotic rate were decreased,p-Akt and Bcl-2 expression was up-regulated and Bax expression was down-regulated in H/R + P group (P ＜ 0.05).Compared with H/R + P group,the cell viability and Bcl-2/Bax ratio were significantly decreased,the LDH activity and apoptotic rate were increased and p-Akt and Bel-2 expression was down-regulated in H/R +P + W group (P ＜ 0.05).Conclusion The mechanism by which propfol postconditioning attenuates H/R-induced injury to cardiomyocytes is related to the activation of PI3K/Akt signaling pathway.

Objective To investigate the effect of mechanical ventilation on the pulmonary microvascular permeability in diabetic mice.Methods Sixty-four male C57/BL6 mice aged 10-12 months,weighing 20-25 g,were randomly assigned into 4 groups (n =16 each):control group (group C); mechanical ventilation group (group M); diabetes group (group D); diabetes mechanical ventilation group (group DM).Diabetes was induced by intraperitoneal streptozotocin 150 mg/kg (in citric acid buffer solution 0.1 mol/L) and confirmed by blood glucose level ＞ 16 mmol/L in groups D and DM,while the equal volume of citric acid buffer solution was given instead of streptozotocin in groups C and M.The animals were anesthetized with intraperitoneal pentobarbital 100 mg/kg and tracheostomized.The animals kept spontaneous breathing for 4 h in groups C and D,while the animals were mechanically ventilated for 4 h in groups M and DM.Eight mice from each group were randomly selected,arterial blood samples were obtained for blood gas analysis,and then the animals were sacrificed and the lung tissues were removed for determination of microscopic examination,W/D lung weight ratio and myeloperoxidase (MPO)activity.Four mice from each group were sacrificed and the pulmonary vascular permeability was determined.Four mice from each group were sacrificed and the primary pulmonary microvascular endothelial cells (PMVECs) were cultured in vitro and confirmed.The PMVEC permeability coefficient was measured using transendothelial [ 14 C ]BSA flux.Results Compared with group C,PaO2 was significantly decreased,and the MPO activity,pulmonary microvascular permeability and PMVECs permeability coefficient were significantly increased in groups M,D and DM,and W/D lung weight ratio was significantly increased in groups M and DM ( P ＜ 0.05).PaO2 was significantly lower,and W/D lung weight ratio,MPO activity,pulmonary microvascular permeability and PMVECs permeability coefficient were significantly higher in group DM than in group D ( P ＜ 0.05).Conclusion The mechanism by which mechanical ventilation induces lung injury may be related to the increase in the pulmonary microvascular permeability in diabetic mice.

Objective To investigate the effects of penehyclidine hydrochloride ( PHC) on lipopolysaccharide (LPS) -induced endothelial cells injury and its mechanism. Methods ECV-304 was cultured in RPMI1640 in a 5% humidified CO2 atmosphere at 37 ℃. Then cultured cells were used to assess the following treatments: control group, LPS group (1 μg/mL) and PHC group(2 μg/mL). At the end of the experiments, supernatant was collected for determination of lactate dehydrogenase ( LDH), and cells were collected for determination of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. And extracellular regulated kinasel/2( ERKl/2)and JNK MAPK (mitogen-activated protein kinases, MAPK) protein expressions were determined using Western blot technique. Analysis of variance (ANOVA) was used for statistical analysis to compare values among all groups. A significant difference was presumed for a probability value < 0.05. Results Compared with control group, LDH leakage [(1642 ± 367) U/L vs (169±33)U/L], the contents of MDA[(13. 2 ± 1. 2) nmol/L vs (7. 2 ±0. 8)nmol/mL] and NO levels [(143.2 ± 10.3) μmol/L vs(85.5 ±4.1) μmol/L], expressions of ERK1/2 and JNK were remarkably increased and SOD activities[(41.2 ±2.7) U/mL vs (61. 1 ±2.8) U/mL] were obviously decreased in LPS group. PHC markedly decreased LDH leakage [(392 ±90) U/L], MDA contents [(8. 6 ± 1. 3) nmol/ mL] and NO levels [(92.1 ±6.6) μmol/L], ERK1/2 activation and enhanced SOD activities [(58.0± 3.0) U/mL]. Conclusions PHC could protect endothelial cells against LPS-induced cell injury. The effect of PHC is likely mediated through inhibition of ERK1/2 MAPK activation.

Objective To evaluate the effects of heme oxygenase-1 (HO-1) mediated by cell penetrating peptide PEP-1 on liverinjury induced by intestinal ischemia/reperfusion (I/R) in rats.Methods Twenty-four male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),intestinal I/R group (group I/R) and PEP-1/HO-1 group (group HO).To establish a model of intestinal I/R,intestines were exteriorized and the superior mesenteric artery was exposed and occluded for 45 min ischemia,and then the clamp was removed for 120 min reperfusion.The PEP-1/HO-1 fusion protein 0.5 mg was injectedvia ihe left iliac vein 30 min prior to ischemia in group HO.The superior mesenteric artery was only exposed but not occluded in group S.At the end of reperfusion,blood samples were collected from the right common carotid artery for measurement of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT) activities.The rats were then sacrificed and livers were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in livertissues.Results Compared with group S,serum AST and ALT activities and MDA content in liver tissues were significantly increased,while SOD activity in liver tissues was decreased in groups I/R and HO (P ＜ 0.05).Compared with group I/R,serum AST and ALT activities and MDA content in liver tissues were significantly decreased,while SOD activity in liver tissues was increased in group HO (P ＜0.05).Liver injury induced by intestinal I/R was significantly attenuated in group HO compared with group I/R (P ＜ 0.05).Conciusioon HO-1 protein mediated by cell penetrating peptide PEP-1 can attenuate liver injury induced by intestinalI/R in rats.

Objective To investigate the effects of heme oxygenase-1 (HO-1) transduced by cell penetrating peptide PEP-1 on renal ischemia/reperfusion (I/R) injury in rats.Methods Eighteen male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 3 groups (n =6 each):sham operation group (group S),renal I/R injury group (group I/R) and fusion protein PEP-1/HO-I + I/R group (group HO).I/R injury was produced by occluding bilateral renal arteries for 45 min followed by reperfusion for 6 h.The fusion protein PEP-1/HO-1 was injected via the left iliac vein 30 min prior to ischemia in group HO.Bilateral renal arteries were only exposed but not occluded in group C.Blood samples were collected from the right common carotid artery at 6 h of reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The malondialdehyde (MDA) content,superoxide dismutase (SOD) activity and HO-1 expression in renal tissues were measured.Results Compared with group S,the levels of MDA,serum BUN and Cr were significantly increased,the SOD activity was decreased,and HO-1 expression was up-regulated in groups I/R and HO (P ＜0.05).Compared with group I/R,the levels of MDA,serum BUN and Cr were significantly decreased,the SOD activity was increased,and HO-1 expression was up-regulated in group HO (P ＜ 0.05).Conclusion HO-1 protein can be successfully transduced into renal tissues by PEP-1 and transduced HO-1 protein reduces renal I/R injury by inhibiting lipid peroxidation response.