Objective To investigate the protective effects of propofol against lung injury following ischemia-reperfusion of hind limbs. Methods Thirty-six Wistar rats weighing 300-350 g were anesthetized with mtraperitoneal 3% pentobarbital 40 mg?kg-1. Bilateral femoral artery and vein were exposed for occlusion of the circulation of the hind limbs. Right internal jugular vein was cannulated for drug administration. The animals were randomly assigned into 3 groups ( n = 12 in each group) : (1) sham-operated group in which bilateral femoral artery and vein were exposed but not occluded; (2) I/R group in which the bilateral femoral artery and vein were occluded for 4h with the atraumatic microclips and the released for 6h reperfusion , and (3) I/R + propofol group received a bolus of 5 mg?kg-1 propofol 10 min before reperfusion followed by propofol infusion at 10 mg?kg-1?h-1. In group 1 and 2 the animals received same amount of normal saline instead of propofol. At the end of 6h reperfusion the animals were sacrificed by bloodletting. The lungs were immediately removed for determination of MDA content, SOD activity, the lung water, iNOS and ICAM-1 expression and microscopic examination. Results I/R significantly increased lung water and MDA content, and expression of iNOS and ICAM-1 and decreased SOD activity, while propofol significantly attenuated these changes induced by I/R of hind limbs. Light microscopic findings in I/R group included alveolar edema, localized pulmonary atelectasis and hemorrhage and large amount of polymorphonuclear infiltration. Electron microscopic examination showed a series of ultrastructural changes such as diffuse irregular thickening of basement membrene, alveolar type Ⅰ cell swelling, alveolar type Ⅱ cell injury associated with emptying of lamella bodies. These changes were significantly less prominent in the rats which received propofol. Conclusion Propofol has protective effects on the lungs against injury induced by I/R of the hind limbs.

Objective To investigate the effects of nicorandil (Nic) pretreatment on myocardial apoptosis in a rabbit model of myocardial ischemia/reperfusion (I/R) .Methods Forty healthy male New Zealand white rabbits aged 4 months weighing 2.0-2.5 kg were randomly allocated to one of 5 groups ( n = 8 each); group 1 sham operation; group 2 I/R; group 3 Nic; group 4 Nic + 5-hydroxydecanoic acid (5-HD) and group 5 Nic + glibenclamide (Gli) . The animals were anesthetized with IV pentobarbital 30 mg?kg-1 and tracheotomized and breathing spontaneously. A piece of thread was placed around the circumflex branch of left coronary artery, which was reversibly occluded for 30 min and released for 120 min reperfusion. In group 3, 4 and 5 a loading dose of 100 ?g?kg-1 Nic was given IV 10 min before myocardial ischemia followed by Nic infusion at 10 ?g?kg-1 ?min-1 until myocardial ischemia was started. In group 4 and S 5-HD 5 mg? kg-1 or Gli 5 mg? kg-1 was given IV 20 min before ischemia. At the end of 120 min reperfusion the animals were killed and the hearts removed. The area of myocardial infarct (AI), and the ischemic risk zone (AR) were determined by computer morphometry. The early apoptotic myocytes were detected by flow cytometry (Beckman, Coulter Co). The expression of caspase-3 protein was determined by immuno-histochemistry. The myocardial ultrastructure was examined with transmission electron microscope.Results Compared to group 2 (I/R) , in nicorandil group (group 3) the size of myocardial infarct and the number of early apoptotic cells were significantly reduced, the ultrastructure of myocardium was well-preserved and the expression of activated caspase-3 protein decreased. The protective effect of Nic preconditioning was greatly inhibited by 5-HD and Gli pretreatment. Conclusion Nicorandil pretreatment exerts protective effect against myocardial I/R injury through activation of mito-KATP C and inhibition of activation of caspase-3.

Objective To observe the effect of multiple monitoring of total intravenous anes-thesia on postoperative cognitive function in elderly patients.Methods Elective 100 patients undergo-ing general anesthesia for abdominal operation,56 males,44 females,aged 65-80 years,ASA physi-cal status Ⅱ or Ⅲ.All patients were divided into multiple monitoring group (group M)and routine monitoring group (group R)by random digital table method,n =50 each.In group M,the anesthesi-ologists modulated anesthetic drugs to make NTI of 37-56 and rSO 2 higher than 50% or not lower than the baseline value by 20%,while in group R the infusion rate of propofol,remifentanil and cisa-tracurium was adjusted by anesthesiologists according to anesthesiologist’s experiences by the pa-tients’monitoring index.Cognitive function of patients in the two groups were evaluated using MMSE 1 d before surgery and 1 d,3 d,7 d,1 month and 3 months after surgery.The occurrence of cognitive dysfunction 7 d,1 month and 3 months after surgery,the postoperative recovery and the dosage of propofol,remifentanil and cisatracurium were recorded.Blood was randomly selected from each group to determine the serum content of S100βand Aβ1-42 by ELISA method at the time point of before surgery (T0 ),one hour after starting surgery (T1 ),the end of surgery (T2 )and postopera-tive 24 hours (T3 ).Results The incidence of postoperative cognitive decline in group M on 1 d (8%vs.22%),3 d (2% vs.1 6%)after surgery were significantly lower than that in group R (P <0.05). Postoperative cognitive dysfunction between the two groups 7 d and 1 month,3 months after surgery has no statistical significance.The dose of propofol [(3.3 ± 0.8)mg · kg-1 · h-1 vs.(3.7 ± 0.7 ) mg·kg-1 ·h-1 ,P < 0.05 ] and cisatracurium [(104 ± 47 )μg · kg-1 · h-1 vs.(124 ± 68 )μg·kg-1 ·h-1 ,P <0.05]in group M was less than that in group R.The time of eye-opening [(10 ±3)min vs.(1 6±6)min,P <0.01],extubation [(13±3)min vs.(22±7)min,P <0.01]and lo-cation [(1 7±4)min vs.(27 ±9)min,P <0.01 ]was shorter in group M.Compared with T0 ,the serum level of S100βprotein was significantly increased in group M at T1 ,T2 and group R at T1-T3 (P <0.05);The level of serum S100βprotein in group M was significantly lower than that in group R (P <0.05).Compared with T0 ,Aβ1-42 protein level was significantly reduced in two groups at T1 and T2 (P <0.05),but there was no significant difference between the two groups.Conclusion Total intravenous anesthesia with multiple monitoring can reduce neural injury and reduce the incidence of early postoperative cognitive decline in elderly patients with abdominal surgery,but has no significant effect on the incidence of POCD.

Objective To observe the effects of obesity on dose-response curve of rocuronium in female patients and calculate ED9 5 of rocuronium.Methods Eighty female patients,aged 18-45 years, falling into ASA grade Ⅰ or Ⅱ,schedualed for elective surgery under general anesthesia,undergoing surgery less than 1.5 h,were included in the study.The patients with body mass index of 20-25 kg/m2 as group N were randomized to divided group N1,group N2,group N3 and group N4.Anoth-er 40 patients with body mass index of 30-35 kg/m2 as group B were randomized to divided group B1, group B2,group B3 and group B4.When the first twitch height of TOF (T1)was 100%,groups N1-N4 and groups B1-B4 patients were injected rocuronium 0.075,0.1,0.1 5,0.3 mg/kg respectively. The first dose of rocuronium in each group,T1 maximum inhibition degree and onset time were re-corded.The relationship between probit-transformed depression of T1 and the logarithm dose of rocu-ronium was analyzed by linear regression.ED50 and ED9 5 of rocuronium in obese and normal body weight patients were calculated.Results Dose-response curve equation of each group were Y1 =3.464X1 -2.23 and Y2 = 3.843X2 - 2.750 respectively(P < 0.05 ).The ED50 and ED9 5 (95% CI)of rocuronium were 0.122 (0.092-0.1 65 )mg/kg and 0.324 (0.242-0.433 )mg/kg in group N,and were 0.103 (0.078-0.133)mg/kg and 0.25 1 (0.1 93-0.326)mg/kg in group B.Conclusion Obesity significantly affects the dose-response curve of young women and can enhance the sensitivity of them to the rocuronium.The ED9 5 of obese patients is 0.25 1 mg/kg.

Objective To investigate the influences of hypothermia on hemodynamics and hemorrheology .Methods The body temperature of 10 mongrel dogs decreased at 35℃ ,and was kept for 30 min, and then warmed to normal degree with physical methods. The parameters of hemodynamics and hemorrheology were measured with the polygraph system (RM 6000, Nihon Kohden).Results Compared with the baselines, 30 min following hypothermia heart rate, mean arterial pressure, cardiac output, maximum rate of rise and decline of pressure(?dp/dtmax),cardiac index, left ventricular stroke work index were significantly reduced, while systemic peripheral resistance , blood viscosity were higher than those under normal body temperature (P

Objective To evaluate the relationship between the mechanism underlying propofol-induced inhibition of migration of human breast cancer cells and glyc olysis.Methods Human breast cancer cell line MDA-MB-231 cells were inoculated in 12-well culture plates at a density of 3× 105 cells/well.After being cultured for 24 h,the cells were divided into 2 groups (n=12 each) by using a random number table:control group (group C) and propofol group (group P).Propofol at the final concentration of 5 μg/ml was added to the culture medium in group P,and the equal volume of phosphate buffer solution was added to the culture medium in group C.At 6 h of incubation,the culture media were changed to the common culture media containing no drugs,and the cells were then incubated for another 24 h.The culture media were collected for determination of glucose concentrations (by oxidase mnethod) and lactate concentrations (by chemical colorimetry).Glucose consumption and lactate production were calculated according to glucose and lactate concentrations.Cells were collected,the expression of lactate dehydrogenase A was detected by Western blot,and the migration of cells was determined by cell scratch test.Results Compared with group C,the consumption of glucose and production of lactate were significantly decreased,the expression of lactate dehydrogenase A was down-regulated,and the migration rate was decreased in group P (P＜0.05).Conclusion The mechanism by which propofol inhibits migration of human breast cancer cells may be associated with inhibition of glycolysis.

Objective To investigate the effects and mechanisms of propofol and dexmedetomidine on neurites and synapses of hippocampal neurons neonatal rats, in vitro. Methods Hippocampal neurons of neonatal Sprague-Dawley rats were cultured 6 days, in vitro and were divided into control group (Group C), solvent of propofol group (Group S), propofol group (Group P), dexmedetomidine group (Group D),propofol and dexmedetomidine group (Group PD), and yohimbine group (Group Y). All groups were cultured for 24 h further. Neuron morphology and the expression of protein were measured. Results After exposing to propofol, we found that the mean total length of neurites of primary cultured hippocampal neurons and synapses and the expression of BDNF, TrkB and CRMP-2 protein were reduced; dexmedetomidine played a protective role. Moreover, yohimbine, partly inhibited neuroprotection of dexmedetomidine. Conclusions Propofol decreases the development of neurites and synapses of hippocampal neurons neonatal rats, in vitro, and dexmedetomidine provides a protective effect on propofol by up-regulating the expression of BDNF, TrkB and CRMP-2. The effect, partly has a concern aboutα2-adrenergic agonist.

Objective To evaluate the role of conventional protein kinase Cγ (cPKCγ)/growthassociated protein-43 (GAP-43) signaling pathway in ketamine-induced apoptosis in hippocampal neurons of developing rats in an in vitro experiment.Methods Primarily cultured hippocampal neurons were seeded in culture plates at a density of 1×10.6 cells/ml and divided into 2 groups (n=10 each) using a random number table:control group (C group) and ketamine group (K group).Group C received no treatment.Ketamine was added with the final concentration of 300 μmol/L in group K.At 12 h of culture or incubation,the apoptosis in hippocampal neurons was detected by flow cytometry.The apoptotic rate was calculated.The expression of cPKCγ,GAP-43 and phosphorylated GAP-43 in hippocampal neurons was measured by Western blot.Results Compared with group C,the apoptotic rates of hippocampal neurons were significantly increased,and the expression of cPKCγ,GAP-43 and phosphorylated GAP-43 was down-regulated in group K (P<0.01).Conclusion The mechanism by which ketamine induces apoptosis in hippocampal neurons of developing rats may be related to inhibition of cPKCγ/GAP-43 signaling pathway activation in an in vitro experiment.

Objective To evaluate the role of Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway in propofol-induced neuroapoptosis in the hippocampus of newborn rats.Methods Experiment Ⅰ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1×106 cells/ml and divided into 2 groups (n=6 each) using a random number table:solvent control group (C group) and propofol group (P group).Propofol was added with the final concentration of 60 μg/ml in group P.Dimethyl sulfoxide was added with the final concentration of 0.04％ in group C.The expression of RhoA and ROCK2 in hippocampal neurons was measured by Western blot at 24 h of incubation.Experiment Ⅱ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1 × 106 cells/ml and divided into 3 groups (n =6 each) using a random number table:solvent control group (C group),propofol group (P group) and propofol plus specific RhoA/ROCK2 signaling pathway blocker Y27632 group (P+Y group).Propofol was added with the final concentration of 60 μg/ml in group P.Propofol at the final concentration of 60 μg/ml and Y27632 at the final concentration of 10 μmol/L were added in group P+Y.Dimethyl sulfoxide was added with the final concentrauon of 0.04％ in group C.At 24 h of incubation,the neuroapoptosis in hippocampi was detected by flow cytometry,and the expression of activated caspase-3 in hippocampal neurons was measured by Western blot.The apoptotic rate was calculated.Results Experiment Ⅰ Compared with group C,the expression of RhoA and ROCK2 in hippocampal neurons was significantly up-regulated in group P (P＜0.05).Experiment Ⅱ Compared with group C,the apoptotic rate of hippocampal neurons was significantly increased,and the expression of activated caspase-3 was up-regulated in P and P+Y groups (P＜0.05 or 0.01).Compared with group P,the apoptotic rate of hippocampal neurons was significantly decreased,and the expression of activated caspase-3 was down-rcgulatcd in group P + Y (P＜ 0.05).Conclusion Activation of RhoA/ROCK2 signaling pathway is involved in propofol-induced neuroapoptosis in hippocampi of newborn rats.

Objective To evaluate the efficacy of regional cerebral oxygen saturation(rSO2) combined with neuroelectrophysiological monitoring in guiding intraoperative blood pressure management in elderly patients undergoing carotid endarterectomy. Methods Thirty patients of both sexes, aged 65-80 yr, of American Society of Anesthesiologists physical statusⅡorⅢ, scheduled for elective carotid endar-terectomy, were divided into 2 groups(n=15 each)using a random number table: control group(group C)and rSO2combined with neuroelectrophysiological monitoring group(group M). During occlusion of carotid artery, the vasoactive drugs were used to make systolic blood pressure(SBP)increase by 20%-30% of the baseline value in group C and to make rSO2not less than 20% of the baseline value, the ampli-tude of somatosensory evoked potential P40 not less than 50% of the baseline value and the amplitude of e-lectroencephalogram voltage not less than 50% in group M. SBP and rSO2were recorded immediately after intubation(T1), at 5 min after anesthesia induction(T2), at 5 min after blocking the carotid artery (T3), at 5 min after opening the carotid artery(T4)and immediately after extubation(T5). Decrease in rSO2≥20% of the baseline value was recorded. The carotid artery occlusion time, myocardial oxygen con-sumption and consumption of vasoactive drugs during occlusion were recorded. Results Compared with group C, SBP was significantly decreased at T3, and the consumption of vasoactive drugs and myocardial oxygen consumption were reduced in group M(P<0.05), and no significant change was found in rSO2at each time point in group M(P>0.05). Decrease in rSO2≥20% of the baseline value was not found in two groups. Conclusion rSO2combined with neuroelectrophysiological monitoring provides guidance for intra-operative blood pressure management in patients undergoing carotid endarterectomy.