Objective To investigate the role of central and peripheral sensitization in remifentanil-induced hyperalgesia in a rat model of inflammatory pain. Methods Twenty-one male SD rats weighing 200-300 g were used in this study. Inflammatory pain was induced by intraplantar injection of 1 % carrageenan 100 fd in the left hindpaw in all animals. The animals were then randomly divided into 3 groups ( n = 7 each): control group (group C) and two remifentanil groups (group R1 , R2) . In R1 and R2 groups remifentanil was infused iv at a rate of 10 and 30 μg-kg-1·min-2 respectively starting from 5 min before till 25 min after carrageenan injection, while in group C normal saline was infused iv instead of remifentanil. Bilateral paw withdrawal threshold to mechanical stimulation with von Frey filament (PWT) was measured before (baseline) and at 1 h, 3 h and 1-7 d after carrageenan injection. Bilateral paw withdrawal latency to noxious thermal stimuli (PWL) was measured before and at 2 h, 4 h and 1-7 d after carrageenan injection. The thickness of the plantar surface of left hindpaw was measured before and at 1 h, 4 h and 1-7 d after carrageenan injection. Results Bilateral PWT was significantly lower at day 1 after carrageenan injection in R, and R2 groups than in group C. The right PWT was significantly lower at 2 d and 4-7 d after carrageenan injection in group R2 than in group R, . There was no significant difference in PWL and thickness of the plantar surface of left hindpaw among the 3 groups. Conclusion Central sensitization is involved in developing and maintaining the remifentanil-induced hyperalgesia in a rat model of inflammatory pain, while peripheral sensitization is not.

Objective To investigate the effects of endaravane on hypoxia-ischemia (HI)-induced brain injury in neonatal piglets. Methods Male piglets 3-7 days old weighing 2.0-3.0 kg were used in this study. Group Ⅰ 10 piglets were randomly collected as sham operation without HI. Twenty piglets with HI were randomly divided into 2 groups (n = 10 each) : group Ⅱ HI and group Ⅲ HI + endaravone. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg, tracheostomized and mechanically ventilated with 30% O_2. Right femoral artery and vein were cannulated. MAP, HR, PET CO_2, blood gases and glucose and rectal temperature were monitored. After 15 min stabilization cardiac arrest was induced by inhalation of hypoxic air (O_2 10%) for 40 min followed by inhalation of 21% O_2 for 5 min. The tracheal tube was then occluded for 7 min. Cardio-pulmonary resuscitation (CPR) was then started until recovery of spontaneous circulation (ROSC). CPR > 3 min was considered a failure. A bolus of endaravone 3 mg/kg was given iv over an hour at 30 min after CPR,followed by continuous infusion at 1.5 mg·kg~(-1)·h~(-1) for 5.5 h in group Ⅲ , while in group Ⅱ vehicle was given instead of endaravone. The neurological function of the animals was evaluated at 48, 72 and 96 h after ROSC and scored (0-154, 0 = normal, 154 = severest dysfunction). The animals were killed at 96 h after ROSC. The brains were removed for microscopic examination of striatum and cortex and determination of 8-hydroxy-2'-deoxyguanine (8-OHdG/OHG) expression in putamen by immuno-histochemistry. Results The neurological function scores were significantly higher at 48 h after ROSC and the number of viable neurons in striatum and sensory cortex were significantly lower and the expression of 8-OHdG/OHG in putamen was significantly higher in group Ⅱ than in group Ⅲ . Conclusion The antioxidant endaravone given after CPR can attenuate Hl-induced brain injury by inhibiting oxidative damage to DNA and RNA.

Objective To investigate the effects of midazolam on hypoxic-ischemic (HI) brain injury in neonatal piglets.Methods Twenty-four newborn male piglets 3-7 days old weighing 1.8-3,0 kg were randomly divided into 3 groups ( n = 8 each): sham group (group S), HI + normal saline group (group HI-S) and HI + midasolam group (group HI-M). The animals of group HI-S and HI-M were subjected to 7 min of hypoxia, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation. At 3 h after restoration of spontaneous circulation (ROSC), animals received i.v. infusion of fentanyl at a rate of 10-30 μg·kg-1·h-1 and pancuroniumat a rate of 0.1-0.2 mg·kg-1·h-1 from 3 h after ROSC to 24 h after ROSC to maintain the anesthesia. In addition, midazolam at a rate of 0.05 mg·kg-1·h-1 wee infused simultaneously until 24 h after ROSC in HI-M group, while the equal volume of normal saline was infused instead in group HI-S and S. Arterial blood samples were taken before hypoxia (baseline), and at 37 min of hypoxia, 5 min of air inspiration, 5 min of asphyxia and 6, 12, and 24 h after ROSC for blood gas analysis, and MAP was monitored at the each time point. Neurological behavior was assessed and scored (NBS) at 48, 72, 96 and 240 h after ROSC. Brains were removed at 10 h after ROSC, the remaining viable neurons in putamen and candate nucleus were counted and the density of viable neurons was determined using light microscopic examination. Results PaO2 was significantly decreased during hypoxia-eephyxia, and PaCO2 was significantly increased, while pH value and MAP were significantly decreased at 5 min of asphyxia in group HI-S and HI-M compared with group S and the baseline (P < 0.05).There were no significant differences in MAP and arterial blood gas analysis at the each time point between group HI-S and HI-M ( P > 0.05). The density of viable neurons in putamen and caudate nucleus was significantly lower, and NBS at 48-96 h after BOSC significantly higher in group HI-S and HI-M than in group S ( P < 0.05). The density of viable neurons in putamen and caudate nucleus was significantly higher and NBS at 72 and 96 h after ROSC significantly lower in group HI-M than in group HI-S ( P < 0.05). Conclusion Midazolam used at the early stage of cardiopulmonary resuscitation can attenuate HI brain injury in neonatal piglets.

Objective To investigate the effects of remffentanil pretreatment on myocardial ischemiareperfusion (I/R) injury in rabbits. Methods Thirty healthy rabbits, aged 12-18 months, weighing 2.5-3.5 kg,were randomly divided into 3 groups (n = 10 each): I/R group, low-dose remifentanil pretreatment group (group R1 ) and high-dose remifentanil pretreatment group (group R2 ). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 6 h of reperfusion in the 3 groups. Remifentanil was infused intavenously at 1.65 and 3.30 μg· kg - 1 · min- 1 for 30 min before ischemia in group R1 and R2 respectively, while equal volume of normal saline was infused instead in group I/R. Blood samples were taken for determination of serum cardiac troponin-Ⅰ (cTnI) and creatine kinase-MB isoenzyme (CK-MB) concentrations before administration (baseline), after administration, at 30 min of ischemia and at 6 h of reperfusion. The rabbits were then sacrificed and hearts removed. Myocardial tissues were obtained for microscopic examination. Results Serum cTnI and CK-MB concentrations were significantly lower in group R1 and R2 than in group I/R and serum cTnI concentration lower in group R2 than in group R1 ( P ＜ 0.01). Remifentanil infusion significantly attenuated the pathologic changes in a dose-dependent manner. Conclusion Remifentanil pretreatment provides protective effect against myocardial I/R injury in rabbits and it is related to the dose.

Objective To investigate the effect of remifentanil pretreatment on lipid peroxidation following acute myocardial ischemia/reperfusion (1/R) in rabbits. MethodsForty healthy adult rabbits of both sexes weighing 1.5-2.5 kg were randomly divided into 5 groups (n = 8 each): group control (group Ⅰ ); group I/R(group Ⅱ ); group morphine pretreatment + I/R (group Ⅲ ); group remifentanil (group Ⅳ ) and group remifentanil pretreatment + I/R (group Ⅴ ). The animals were anesthetized with intraperitoneal 2％ pentobarbital 45 mg/kg and were mechanically ventilated after tracheal intubation. PET CO2 was maintained between 35-45 mm Hg. Myocardial I/R was induced by iv pituitrin 2.5 U/kg in group Ⅱ , Ⅲ and Ⅴ. In group Ⅰ and Ⅳ normal saline 0.3 ml/kg was injected iv instead of pituitrin. In group Ⅲ morphine 3.3 mg/kg was injected iv at 30 min before iv pituitrin. In group Ⅳ and V remifentanil was infused at 3.3 μg· kg-1 ·min-1 for 30 min before iv normal saline and pituitrin.Venous blood samples were taken before (baseline) and at 24 h and 48 h after iv pituitrin for determination of serum cTnI concentration. The myocardial specimens were taken at T3 after blood sampling for microscopic examination and determination of SOD activity and MDA content. ResultsIntravenous pituitrin 2.5 U/kg significantly increased serum cTnI concentration and myocardial MDA content and decreased myocardial SOD activity in group Ⅱas compared with group Ⅰ . Morphine or remifentanil preatment significantly attenuated the myocardial I/R-induced changes mentioned above. Microscopic examination showed that myocardial tissue damages were ameliorated in group V as compared with group Ⅱ . ConclusionRemifentanil pretreament can attenuate acute myocardial ischemic injury by inhibiting lipid peroxidation.

OBJECTIVETo analyze the risk factors of liver metastasis in patients after radical resection of pancreatic cancer.

METHODSOne hundred and twenty-four patients with non-metastatic, resectable pancreatic cancer treated in our department between 2006 and 2012 were included in this study. All of these patients underwent resection of the primary tumor combined with extensive lymph node dissection. The development of postoperative liver metastases was carefully followed up, and the clinicopathological factors and molecular characteristics were evaluated by univariate analysis and multivariate logistic regression using SPSS 16.0 software.

RESULTSForty-eight cases of liver metastases were found among the 124 cases of pancreatic cancer after radical surgery (38.7%). The rate of liver metastasis of pancreatic cancer after radical surgery in the age groups < 40, 40-60, and > 60 were 68.8%, 33.3% and 35.1%, respectively. The rate of liver metastasis in the body mass index (BMI) group < 20 kg/m2, 20-25 kg/m2, and > 25 kg/m2 were 21.6%, 44.1% and 52.6%, and the rate of liver metastasis in the time between the onset and diagnosis groups ≥ 3 months and < 3 months were 59.4% and 31.5%, respectively. The rate of liver metastasis in patients with preoperative fatty liver was 14.3% and it was 43.7% in patients without preoperative fatty liver. The rate of liver metastasis in patients of histological high, medium and low grade was 10.0%, 35.4% and 49.0%, respectively. The rate of liver metastasis in patients with venous tumor thrombus was 68.8% and it was 34.3% in patients without venous tumor embolus. The rate of liver metastasis in patients with postoperative chemotherapy was 31.2% and it was 51.1% in patients without postoperative chemotherapy. All those differences had statistical significance (P < 0.05). Univariate analysis revealed that age, body mass index (BMI), time between the onset and diagnosis, preoperative fatty liver, histological grading, tumor invasion depth, venous tumor embolus, and postoperative chemotherapy were significantly related to postoperative liver metastasis. Multivariate analysis revealed five statistically independent risk factors for postoperative liver metastasis: BMI, time between onset and diagnosis, preoperative fatty liver, histological grading, and venous tumor embolus.

CONCLUSIONSOur data suggest that patient's BMI, time between onset and diagnosis, histological grade, and venous tumor embolus are significantly correlated with postoperative liver metastases in patients with pancreatic cancer. Pancreatic cancer patients with preoperative fatty liver have less postoperative liver metastasis.

Adult ; Aged ; Body Mass Index ; Humans ; Liver Neoplasms ; secondary ; Lymph Node Excision ; Middle Aged ; Pancreatic Neoplasms ; pathology ; surgery ; Regression Analysis ; Risk Factors

Objective To evaluate the effects of different doses of propofol on traumatic brain injury in rats .Methods Forty-eight healthy male Sprague-Dawley rats , aged 7-8 weeks , weighing 270-320 g , were randomly divided into 6 groups ( n=8 each ) using a random number table :sham operation group (group S ) , traumatic brain injury group (group I) ,fat emulsion group (group F) and low-dose propofol group (group L) , medium-dose propofol group (group M ) ,and high-dose propofol group (group H ) .Traumatic brain injury model was established according to the method described by Feeney .In group S ,0.9% normal saline was infused into the left femoral vein at 3.49 ml·kg-1 ·h-1 .In I ,F ,L ,M and H groups ,0.9% normal saline ,20% fat emulsion 3.49 ml·kg-1 ·h-1 ,and propofol 17.46 ,34.92 and 69.84 mg·kg-1 ·h-1 were infused into the left femoral vein ,respectively .Blood samples were collected from the right common carotid artery at 15 and 60 min of infusion (T1-2 ) for determination of serum S100β protein concentrations . The rats were then sacrificed after collecting blood samples at T2 and brains were removed for microscopic examination of the pathological changes of the cerebral cortex (light microscope ) and ultrastructure of neurons in the cerebral cortex (transmission electron microscope) .Results The serum S100β protein concentrations were significantly higher at T1 ,2 in the other five groups than in group S ( P<0.05 ) .Compared with I and F groups ,the serum S100βprotein concentrations were significantly decreased at T1 ,2 in L ,M and H groups ( P<0.05) .Compared with group L ,the serum S100βprotein concentrations were significantly decreased at T2 in M and H groups , and the serum S100β protein concentrations were increased at T1 in H group ( P< 0.05 ) . The serum S100β protein concentrations were significantly higher at T1 ,2 in H group than in group M ( P<0.05 ) .Light microscopic examination showed that nucleus condensation , cell necrosis , and cell edema were significantly attenuated in L ,M , and H groups as compared with group I;normal neurons could be found in group M .Transmission electron microscopic examination showed that the severity of neuronal damage was significantly attenuated in L ,M ,and H groups as compared with group I .Conclusion Different doses of propofol can reduce traumatic brain injury in rats .

Objective To analyse tratment strategies and to evaluate the relation between different therapies and survival rate of patients of with asynchronous liver metastases after pancreatic cancer surgery (PCLM).Methods From January 2006 to January 2012,48 patients with PCLM were included in this study,and their medical records were retrospectively analyzed.Results Among the 48 patients,27 cases of liver metastases were found within six months after surgery,and the survival rate for 1,3 and 5 years was 22.2％,3.7％ and 0％,respectively,with the median survival of 6 months,and 21 cases of liver metastases were found after six months,and the survival rate for 1,3 and 5 years was 85.7％,30.6％ and 9.2％,with the median survival of 15 months,and the difference between the two groups was statistically significant (P ＜ 0.01).After pancreatic cancer surgery and adjuvant gemcitabine chemotherapy,the probability of liver metastases was 33.3％ (8/24) within six months,the median disease-free survival time was 8 months and the disease-free survival rate for 1,3 and 5 years was 20.8％,4.3％ and 0％.For patients without adjuvant gemcitabine chemotherapy,the probability of liver metastases was 79.2％ (19/24),the median disease-free survival time was 3 months and the disease-free survival rate for 1,3 and 5 years was 4.2％,0％ and 0％,and the difference between the two groups was statistically significant (P ＜ 0.01).The overall survival for patients undergoing resection of liver metastases combined with gemcitabine treatment was better than the other groups (P ＜ 0.01).And the overall survival for patients undergoing transhepatic arterial embolization (TACE) combined with gemcitabine treatment was better than TACE group,gemcitabine group or the observation group (P ＜0.05).There were no difference in overall survival between TACE group,gemcitabine group and observation group.Conclusions Pancreatic cancer patients who develop liver metastasis within six months after surgery have poor prognosis,but postoperative chemotherapy can delay the development of liver metastasis.For patients with resectable lesion,resection of asynchronous liver metastasis is the treatment of choice,and TACE combined with gemcitabine has better efficacy than that of single treatment.

Objective To investigate the effects of pretreatment with remifentanil on hemorrhagic shock (HS)-induced acute liver injury in rabbits.Methods Thirty-two New Zealand white rabbits,weighing 2.0-2.5 kg,were randomly divided into 4 groups (n=8 each): sham operation group (group S) ; group HS,low-dose remifentanil group (group RL) ; high-dose remifentanil group (group RH).Remifentanil was infused at 0.66 and 1.32 μg· kg-1 · min-1 for 145 min in groups RL and RH respectively,while the equal volume of normal saline was infused in group C.HS was induced by withdrawing blood from the left femoral artery at 15 min after continuous infusion of normal saline or remifentanil and mean arterial pressure (MAP) was reduced to 40 mm Hg.MAP was reduced to 35-45 mm Hg and maintained at this level for 120 min in groups HS,RL and RH.Blood samples were taken for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities before administration (T0),immediately before blood letting (T1),and at 10,30,60 and 90 min after blood letting (T3-6).The animals were then sacrificed and the livers were immediately removed for microscopic examination.Results Compared with group S,the serum ALT activity at T5 and T6 and serum AST activity at T4-T6 were significantly increased in the other three groups (P ＜ 0.05).Compared with group HS,the serum ALT activity at T5 and T6,and serum AST activity at T4-T6 were significantly decreased in group RH,and no significant change was found in group RL (P ＞ 0.05).Compared with group RL,the serum ALT activity at T5 and T6,and serum AST activity at T4-T6 were significantly decreased in group RH (P ＜ 0.05).The serum ALT activity at T5 and T6 and serum AST activity at T4-T6 were significantly increased in groups HS,R and RH than those at T0 (P ＜ 0.05 or 0.01).The patho1ogical injury was attenuated in group RH compared with groups HS and RL.Conclusion Remifentanil pretreatment can attenuate HS-induced acute liver injury in rabbits,and the effect is related to the dose.

Objective To investigate the effect of liver cirrhosis on the potency of propofol for sedation in rats. Methods Fifty-eight male SD rats, aged 10-12 weeks, weighing 180-220 g, were randomly divided into 3 groups: control group (group C, n = 18), mild liver cirrhosis group (group M1, n =20) and severe liver cirrhosis group (group M2, n = 20). The model of liver cirrhosis was established using four factors described by Chen et al. After successful establishment of the model, propofol was injected intravenously. The dose of propofol was determined by up-and-down sequential method for loss of righting reflex. The dose of propofol was 5.912 mg/kg in the first rat and the ratio of the doses between the two consecutive rats was 0.85. ED50 of propofol was calculated using up-and-down sequential method. Results ED50 of propofol was significantly lower in group M1 and M2 than in group C and in group M2 than in group M1 ( P ＜ 0.05 or 0.01 ). Conclusion The liver cirrhosis can enhance the potency of propofol for sedation in rats.