Objective To investigate the effect of hyperbaric oxygen ( HBO) preconditioning on activation of plasma protein C in a rat model of asphyxial cardiac arrest?resuscitation. Methods A total of 105 adult male Sprague?Dawley rats, aged 70-90 days, weighing 260-320 g, were randomly divided into 3 groups: cardiac arrest group ( group CA, n=5) , cardiac arrest?resuscitation group ( group CA∕R, n=50) , and hyperbaric oxygen preconditioning group ( group H, n=50 ) . Cardiac arrest was induced by campling the endotracheal tube at the end of expiration. The animals underwent HBO preconditioning once a day for 3 consecutive days before cardiac arrest was induced in group H. The rats were placed in the HBO chamber, 10 min later the pressure was increased at a constant rate until the hyperbaric oxygen reached 2 atmosphere absolute, and maintained at this level for 45 min, after the oxygen concentration>95%, and then the pressure was decreased at a constant rate ( within 20 min) until the normal pressure was reached. The rats underwent no resuscitation in group CA. Five rats were selected from CA∕R and H groups at 3, 6, 12 and 24 h after restoration of spontaneous circulation, and at 30 min of cardiac arrest in group CA, and blood samples were taken from the abdominal aorta for determination of the plasma activated protein C ( APC) concentrations. The time from asphyxia to cardiac arrest, time for spontaneous regular cardiac rhythm, and successful resuscitation were recorded. Results Compared with group CA, the plasma APC concentrations were significantly decreased at each time point after restoration of spontaneous circulation in CA∕R and H groups ( P<0.05) . Compared with group CA∕R, the time from asphyxia to cardiac arrest was significantly prolonged, the time for spontaneous regular cardiac rhythm was shortened, the success rate of resuscitation was increased, and the plasma APC concentrations were increased at each time point after restoration of spontaneous circulation in group H ( P<0. 05 ) . Conclusion HBO preconditioning can promote activation of plasma protein C after resuscitation in a rat model of asphyxial cardiac arrest, and is helpful in improving hypercoagulation.

Objective To evaluate the effect of sevoflurane on brain injury in a pig model of hem?orrhagic shock in hypothermia environment. Methods Twenty?four Bama miniature pigs, weighing 21-25 kg, aged 3-5 months, were equally randomized into 3 groups using a random number table: sham opera?tion group (group Sham);hemorrhagic shock (group HS); sevoflurane group (group Sev). The animals were anesthetized, tracheostomized and mechanically ventilated. Bilateral femoral arteries were cannulated for continuous mean arterial pressure, and heart rate monitoring, blood?letting and blood sampling. A cath?eter was inserted into the right internal jugular vein for body temperature monitoring. After the animals were awake, they were placed in an environment at-15℃. Hemorrhagic shock was induced by withdrawing 40%of blood volume from the right femoral artery within 15 min ( 30 ml∕kg) in HS and Sev groups. The animals inhaled 2% sevoflurane for 30 min after establishment of the model in group Sev. Before hemorrhagic shock, and at 30, 60, 90, 120, 180 and 240 h after hemorrhagic shock ( T0?6 ) , blood samples were collected from the femoral artery for determination of plasma tumor necrosis factor?alpha ( TNF?α) , interleukin?6(IL?6), nuclear factor kappa B (NF?κB), S100β protein and neuron?specific enolase (NSE) concentra?tions. After blood sampling at T6 , the animals were sacrificed, and brains were removed for microscopic examination of pathological changes, and for determination of Toll?like receptor 4 ( TLR4) expression by Western blot. Results Compared with group Sham, the plasma NSE, S100β protein, TNF?α, IL?6 and NF?κB concentrations were significantly increased at T2?6 , and TLR4 expression was up?regulated at T6 in HS and Sev groups ( P<0?05) . Compared with group HS, the plasma NSE, and S100βprotein concentra?tions were significantly decreased at T4?6 , the plasma TNF?α, IL?6 and NF?κB concentrations were de?creased at T2?6, and TLR4 expression was down?regulated at T6 (P<0?05), and the pathological changes were significantly attenuated in group Sev. Conclusion Sevoflurane can mitigate brain injury in a pig mod?el of hemorrhagic shock in hypothermia environment, and the mechanism may be related to inhibited TLR4∕NF?κB signaling pathway and attenuated inflammatory responses.

Objective To evaluate the effect of BML?111 on ventilator?induced lung injury in rats. Methods Forty?eight healthy male Sprague?Dawley rats, weighing 200-250 g, aged 6-8 weeks, were randomized into 6 groups ( n=8 each) using a random number table: control group ( C group) , low tidal volume (VT) group (LVTgroup), high VT group (HVTgroup), low dose BML?111 group (BL group), high dose BML?111 group ( BH group) , and BML?111 plus BOC?2 ( lipoxin A4 receptor antagonist) group ( BOC?2 group) . Group C kept spontaneous breathing after tracheotomy, and received no mechanical venti?lation. The rats in the other 5 groups were mechanically ventilated ( respiratory rate 80 breaths∕min, frac? tion of inspired oxygen 21%, positive end?expiratory pressure 0) . The VT was 6 ml∕kg in group LVT , or 20 ml∕kg in HVT, BL, BH and BOC?2 groups. BML?111 0?1 and 1?0 mg∕kg were injected intraperitoneally during ventilation in BL and BH groups, respectively. In group BOC?2, BOC?2 50 μg∕kg was injected in?traperitoneally before ventilation, and BML?111 1?0 mg∕kg was injected intraperitoneally during ventilation. Arterial blood samples were collected at 4 h of ventilation, arterial oxygen partial pressure ( PaO2 ) was de?termined. Then animals were sacrificed by exsanguination. Bronchoalveolar lavage fluid ( BALF) of the left lung was collected for determination of neutrophil count, and the level of neutrophil was calculated. The right lung tissue specimens were obtained for microscopic examination, and for determination of wet∕dry lung weight ratio ( W∕D ratio ) , myeloperoxidase ( MPO ) activity, and contents of malondialdehyde ( MDA) , monocyte chemoattractant protein?1 ( MCP?1) , tumor necrosis factor?alpha ( TNF?α) , interleu?kin?1beta ( IL?1β) and IL?6. Results Compared with group C, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group HVT ( P<0?05) , and no significant change was found in the variables mentioned above in group LVT ( P>0?05) . Compared with group HVT , PaO2 was significantly increased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were decreased in group BH, and the contents of TNF?α, IL?1βand IL?6 were significantly decreased ( P<0?05) , and no significant change was found in the other variables in group BL ( P>0?05) . Compared with group BH, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group BOC?2 (P<0?05). The pathological changes were significantly attenuated in group BL as compared with HVT and BOC?2 groups. Conclusion BML?111 can attenuate ventilator?induced lung injury in rats, and activated lipoxin A4 receptors are involved in the mechanism.

Objective To evaluate the effect of remifentanil preconditioning ( RP ) on intestinal is?chemia?reperfusion ( I∕R) injury in rats and its relationship with opioid receptors. Methods Seventy?two Sprague?Dawley rats, aged 6-7 weeks, weighing 250-280 g, were randomly divided to 9 groups ( n=8 each): sham operation group (S), intestinal I∕R group (group I∕R), RP group, different opioid receptor antagonists groups (N, BNI and CTOP groups), and opioid receptor antagonists + RP groups (N+RP, BNI+RP and CTOP+RP groups) . Intestinal I∕R was produced by clamping the superior mesenteric artery for 1 h followed by 2 h reperfusion in all the groups except group S. RP was induced by 3 cycles of 5 min infusion of remifentanil 0?2 μg·kg-1 ·min -1 followed by 5 min infusion of normal saline before ischemia. Naltrindole (δ?receptor antagonist, 5 mg∕kg) , nor?binaltorphimine (κ?receptor antagonist, 5 mg∕kg) and CTOP (μ?receptor antagonist, 1 mg∕kg) were administered before RP. At 2 h of reperfusion, blood sam?ples were collected from the cardiac apex for determination of serum diamine oxidase ( DAO) activity. Intes? tinal tissues were then removed for microscopic examination. Intestinal damage was assessed and scored ac?cording to Chiu. Apoptosis in intestinal mucosal epithelial cells was detected using TUNEL assay, and ap?optosis index was calculated. The expression of activated caspase?3 in intestinal mucosal epithelial cells was measured by Western blot. Results Compared with group S, the serum DAO activity, Chiu′s score, and apoptosis index were significantly increased, and the expression of activated caspase?3 was up?regulated in I∕R and RP groups ( P<0?05) . Compared with group I∕R, the serum DAO activity, Chiu′s score, and ap?optosis index were significantly decreased, and the expression of activated caspase?3 was down?regulated in RP, BNI+RP and CTOP groups (P<0?05), and no significant change was found in the parameters men?tioned above in N, N+RP, BNI and CTOP+RP groups (P>0?05). Compared with group RP, the serum DAO activity, Chiu′s score, and apoptosis index were significantly increased, and the expression of activa?ted caspase?3 was up?regulated in N+RP and CTOP+RP groups ( P<0?05) , and no significant change was found in the parameters mentioned above in group BNI+RP ( P>0?05) . Conclusion RP can mitigate in?testinal I∕R injury in rats, and the mechanism is related to the anti?apoptotic effect mediated by activation ofδ?and μ?opioid receptors, but not κ?opioid receptors.

Objective To evaluate the effect of cerebral palsy factor on the sensitivity of postopera?tive pain in the pediatric patients. Methods Twenty?five pediatric patients with cerebral palsy of both se?xes, of American Society of Anesthesiologists physical statusⅠorⅡ, aged 3-7 yr, weighing 11-25 kg, scheduled for elective lower abdominal or lower extremity surgery, served as cerebral palsy group ( group P). Another 25 pediatric patients without cerebral palsy of both sexes, of American Society of Anesthesiol?ogists physical status Ⅰ orⅡ, aged 3-7 yr, weighing 11-25 kg, served as control group ( group C) . At 2 h after surgery, pain was evaluated by using CRIES ( crying, requires O2 saturation, increased vital sign, expression and sleeplessness) . Peripheral venous blood samples were collected before surgery, and at 2 and 24 h after surgery, and the concentrations of plasmaβ?endorphin were measured by radio?immunity method, and the concentration of plasma catecholamine ( adrenaline) was determined by high performance liquid chromatography. Results Compared with the value before surgery, the plasma concentrations of β?endorphin were significantly decreased, and the concentrations of plasma catecholamine were increased after surgery in the two groups (P < 0?01). Compared with group C, the CRIES score was significantly in?creased after surgery, the concentration of plasmaβ?endorphin was decreased before and after surgery, and the concentration of plasma catecholamine was increased after surgery in group P ( P< 0?05 or 0?01) . Con?clusion The sensitivity of postoperative pain is increased in the pediatric patients with cerebral palsy.

Objective To compare remifentanil?propofol target?controlled infusion ( TCI ) with sufentanil?propofol TCI for sedation and analgesia in the patients undergoing local anesthesia. Methods Sixty patients, aged 17?54 yr, with body mass index <30 kg∕m2, scheduled for elective plastic surgery underlocal anesthesia, were equally and randomly divided into remifentanil group (group R) and sufentanil group(group S) by using a random number table. Remifentanil (the initial target plasma concentration 1?? 0ng∕ml) and propofol (the initial target plasma concentration 1?? 0 μg∕ml) were given by TCI in group R.Sufentanil (the initial target plasma concentration 0?? 10 ng∕ml) and propofol (the initial target plasma con?centration 1?? 0 μg∕ml) were given by TCI in group S. The target plasma concentration was adjusted to main?tain the modified Observer′s Assessment of Alertness∕Sedation Scale score of 2 or 3. The occurrence of painresponses, hypoxemia, bradypnea and∕or apnea was recorded during operation. The total amount of propofolconsumed was calculated. Results There was no significant difference in the incidence of pain response,hypoxemia, bradypnea and∕or apnea, and total amount of propofol consumed between the two groups (P >0?? 05). Conclusion Remifentanil?propofol TCI provides similar sedative and analgesic efficacy to that a?chieved by sufentanil?propofol TCI in the patients undergoing local anesthesia.

Objective To determine the median effective dose ( ED50 ) of sufentanil blunting re?sponses to double?lumen endotracheal intubation when combined with propofol. Methods American Socie?ty of Anesthesiologists physical statusⅠorⅡpatients, aged 45-64 yr, with body mass index<30 kg∕m2 , of Mallampati classⅠor Ⅱ, undergoing elective thoracic surgery under general anesthesia, were enrolled. Sufentanil was injected intravenously with the initial dose of 0?6μg∕kg, and then propofol 1 mg∕kg was in?jected slowly until the patients lost consciousness. After loss of consciousness, cisatracurium 0?3 mg∕kg was injected intravenously, and propofol 0-1?5 mg∕kg was injected intermittently to maintain bispectral index value ranging from 45 to 55. A double?lumen endotracheal tube was placed at 3 min after administrattion of muscle relaxants. The dose of sufentanil was determined by modified Dixon′s up?and?down method. The dose of sufentanil was increased∕decreased by 0?1 μg∕kg in the next patient. At least 6 independent cross?over pairs were observed, and the test was completed. The response to double?lumen endotracheal intuba?tion was defined as an increase in mean arterial pressure ≥ 20% of the baseline value and∕or heart rate >90 bpm within 5 min after intubation. The ED50 and 95% confidence interval of sufentanil blunting the re?sponses to double?lumen endotracheal intubation were calculated using probit method. Results The ED50 ( 95% confidence interval) of sufentanil blunting the responses to double?lumen endotracheal intubation was 0?464 (0?309-0?580) μg∕kg. Conclusion When combined with propofol, the ED50 of sufentanil blun?ting the responses to double?lumen endotracheal intubation is 0?464 μg∕kg.

Objective To compare the accuracy of Marsh model and Schnider model for propofol target?controlled infusion ( TCI) system. Methods Eighty patients, aged 20-60 yr, of American Society of Anesthesiologists physical status ⅠorⅡ, with body mass index of 17?5-28?0 kg∕m2 , scheduled for e?lective gynecological operation under general anesthesia, were equally and randomly divided into either Marsh model group ( group M) or Schnider model group ( group S) using a random number table. The target plasma concentration was set at 3 μg∕ml in both groups. During TCI and at different time points after the end of TCI, the blood samples were collected for determination of blood propofol concentrations by high per?formance liquid chromatography with fluorescence detector. The difference between measured and predicted concentrations (△C) at each time point was calculated. The median performance error ( MDPE) , median absolute performance error ( MDAPE) , and wobble of propofol TCI system were calculated in each group. Results In M and S groups, the MDPE was 9. 90% and 14?00%, respectively; the MDAPE was 11?43% and 14?49%, respectively;the wobble was 7?77% and 7?79%, respectively. There was no sig?nificant difference in △C at each time point during TCI between group M and group S (P>0?05). After TCI was stopped, △C at each time point was significantly lower in group M than in group S ( P<0?05) . Conclusion Marsh model provides higher accuracy than Schnider model for propofol TCI system in the pa?tients undergoing gynecological operation.

Objective To evaluate the role of spinal c?Jun N?terminal kinase ( JNK ) signaling pathway in incisional pain in rats. Methods Sixty?three adult male Sprague?Dawley rats, weighing 200-250 g, were randomly divided into 3 groups ( n=21 each) using a random number table: incisional pain group ( IP group) , dimethyl sulfoxide ( DMSO) group, and JNK inhibitor SP600125 group ( SP group) . A 1?cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in anesthetized rats. In group DMSO, 10% DMSO 10 μl was injected intrathecally at 30 min before surgery. In group SP, SP600125 25 μg (in 10 μl of 10% DMSO) was injected intrathecally at 30 min before sur?gery. Six rats in each group were sacrificed, and the mechanical paw withdrawal threshold ( MWT) and thermal paw withdrawal latency ( TWL) were measured at 24 h before establishment of the model and 2, 6, 24, 48 and 72 h after establishment of the model. After measurement of the pain threshold at 24 h before establishment of the model and 6, 24, 48 and 72 h after establishment of the model, the lumbar segment of the spinal cord was removed for determination of the expression of phosphorylated JNK ( p?JNK) by im?munofluorescence. Results The MWT was significantly lower, the TWL was shorter, and the expression of p?JNK was lower at each time point after establishment of the model than at 24 h before establishment of the model in group IP (P<0?05). Compared with group IP, the MWT was significantly increased, the TWL was prolonged, and the expression of p?JNK was down?regulated at each time point after establishment of the model in group SP ( P<0?05) , and no significant change was found in the parameters mentioned a?bove in group DMSO ( P>0?05) . Conclusion Spinal JNK signaling pathway is involved in the develop?ment and maintenance of incisional pain in rats.

Objective To evaluate the effect of dexmedetomidine on spinal p38 mitogen?activated protein kinase ( p38MAPK) expression during remifentanil?induced hyperalgesia in rats with incisional pain. Methods Forty?eight healthy male Sprague?Dawley rats, aged 6 weeks, weighing 220-250 g, were ran?domly divided into 4 groups ( n= 12 each) using a random number table: control group ( group C) , inci?sion pain group ( group IP ) , incision pain + remifentanil group ( group IP+R ) , and incision pain +remifentanil + dexmedetomidine group ( group IP+R+D) . After successful establishment of the model of in?cisionsal pian, remifentanil 1?0μg∕kg was infused for 4 h via the tail vein in group IP+R; remifentanil 1?0μg∕kg was infused for 4 h via the tail vein, and dexmedetomidine 10μg∕kg was simultaneously infused for 4 h via the jugular vein in group IP+R+D; the equal volume of normal saline was infused for 4 h via the tail and jugular veins in C and IP groups. The mechanical paw withdrawal threshold ( MWT) was measured at 24 h before operation ( T0 ) , and at 4, 6, 24 and 48 h after the end of drug infusion ( T1?4 ) . After meas?urement of MWT at T4 , the expression of p38MAPK was determined using immuno?histochemistry. Results was up?regulated at T4 in IP and IP+R groups ( P<0?05) , and no significant change was found in the MWT and expression of p38MAPK in group IP+R+D (P>0?05). Compared with group IP, the MWT was signifi?cantly decreased at T1?4, and the expression of p38MAPK was up?regulated at T4 in group P+R, and the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D (P<0?05). Compared with group IP+R, the MWT was significantly increased at T1?4, and the expression of p38MAPK was down?regulated at T4 in group IP+R+D ( P<0?05) . Conclusion The mecha?nism by which dexmedetomidine reduces hyperalgesia induced by remifentanil is related to down?regulation of spinal p38MAPK expression in the rats with incisional pain.