Objective To investigate the effect of acute hypervolemic hemodilufion (AHHD) on EC50 of propofol by target-controlled infusion (TCI) for loss of consciousness (LOC). Methods Sixty ASA Ⅰ or Ⅱ patients aged 18-64 yr scheduled for vertebral eolunm or total hip replacement surgery were randomly divided into 4 groups (n = 15 each) : group Ⅰ target plasma concentration of propofol (Tp) ;group Ⅱ target effect-site concentration of propofol (Te) ;group Ⅲ AHHD + Tp and group Ⅳ AHHD + Te. All the patients recoived iv infusion of lactated Ringer's solution 0.7 ml·kg-1 ·h-1 via peripheral vein for 30 min. At the same time 4% gelofusion 15 ml/kg was infused over 30 min via internal jugular vein in group Ⅲ and Ⅳ. At the end of gelofusine infusion TCI of propofol was started. The initial target concentration was set at 1.2 μg/ml. After the target concentration was steadily maintained for 30 s, the consciousness of the patients was evaluated by an anesthesiologist not involved in the study using OAA/S scale. The target concentration was increased in 0.3 μg/ml increment until the patients lost consciousness (OAA/S = 0). The target plasma concentration and effect-site concentration were then recorded. EC50 and 95% confidence interval (CI) of propofol for LOC were calculated by probit analysis. Results The ECho (95 % CI) of propofol for patients in group Tp, Te, AHHD + Tp and AHHD + Te (group Ⅰ-Ⅳ) were 3.74 (3.46-4.16), 2.32 (2.17-2.42), 4.12 (3.81-4.32) and 2.38 (2.14-2.56) μg/ml respectively. EC50 was significantly higher for loss of consciousness in AHHD + Tp group (group Ⅲ)than in Tpgroup (group Ⅰ), but there was no significant difference in EC50 between group Te and group AHHD + Te. Conclusion AHHD can increase the EC50 of target plasma concentration of propofol by TCI for LOC but has no effect on EC50 of target effect-site concentration.

Objective To investigate the role of spinal cord opioid receptors in the antinocieeptive effect of propefol in rats. Methods Male SD rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. Intratbecal (IT) catheter was placed at L5～6 interspace. Correct placement was confirmed by lower extremity motor block after injection of 2% lidocaine 15 μl via the iv catheter. Animals which were lame or paralyzed were excluded. Ninety SD rats in which IT catheters were successfully placed were randomly divided into 9 groups (n = 10 each): group Ⅰ propofol 10μg IT (P);group Ⅱ dimethyl suipbexide (DMSO-solvent for propofol) 5 μl IT (D);group Ⅲ artificial cerebral spinal fluid (ACSF) 5 μl IT;group Ⅳ propoful 10 μl + naloxone 15 μg IT (PN);group Ⅴ DMSO 5 μl IT + naloxone 15 μg IT (DN);group Ⅳ propofol 10μg IT + CTOP Ⅰμg IT (PC);group Ⅶ DMSO 5 μl IT + CTOP 1μg IT (DC);group Ⅷ propofol 10 μg IT + ICI 174, 864 1 μg IT (PI) and group ⅨDMSO 5 μl 1T + ICI 174, 864 1 μg IT (DI). In group Ⅳ-Ⅸ naloxone or CTOP (μ-receptor antagonist) or ICI 174, 864 (δ-receptor antagonist) was injected 5 min after propofol/DMSO. Pain threshold was measured before the first drug administration (T0) and at 10 min (T1), 20 min (T2) and 40 min (T3) after the first drug administration using hot water tail-withdrawal test. The latency for withdrawal of the tail from hot water was recorded. Results The pain threshold was significantly higher in group P, PN, PC and PI than in group D, DN, DC and DI respectively. The pain threshold was significantly increased at T1.2 compared with the baseline value at T0 in group P, PN, PC and PI. The pain threshold was significantly lower at T3 than at T1 and T2 in group P, PN, PC and PI. The pain threshold was significantly lower after drug administration in group PN and PI than in group P and PC. Conclusion Spinal cord δ-oploid receptors are involved in the anfinocicepfive effect of propofol.

Objective To investigate the changes in BIS values induced by TCI of sufentanil at different target concentrations (Cr) during propofol anesthesia. Methods Fifty ASA Ⅰ or Ⅱ patients aged 18-57 yr undergoing elective surgery under general anesthesia were randomly divided into 5 groups (n = 10 each) based on CTof sufentanil: 0.07, 0.10, 0.14, 0.20 and 0.28 ng/ml. BIS, ECG, HR, MAP, SpO2, PET CO2 were continuously monitored. Anesthesia was induced with propofol TCI. The initial target plasma concentration (Cp) was set at 3.0 μg/ml. If the patient remained conscious 5 rain after the equilibrium between Cp and target effect-site concentration (Ce) was achieved, the Cp of propofol was increasing in increments of 0.3 μg/ml until consciousness was lost (LOC). Propofoi TCI was maintained at this level and Cp and Ce were recorded. TCI of safentanil was then started at the different Cp set in the 5 groups. When the equilibrium between Cp and Ce of safentanil was achieved, tracheal intubation was facilitated with succinyl choline 1.5 mg/kg and the patients were mechanically ventilated (VT= 8-10 mi/kg, RR = 8-12 bpm, PETCO2 = 30-35 mm Hg). BIS value, HR, MAP, SP and DP were recorded before induction of anesthesia at LOC (T0) and 1,2, 3, 4, 5 and 6 min after sufentanil TCI was started. Results There was no significant difference in Cp and Ce of propofol at LOC (T0) among the 5 groups. BIS value was decreasing after the beginning of TCI of sufentanil and was significantly lower than the BIS value at T0. The changes in BIS value was negatively correlated with the Cp and Ce of sufentanil. Conclusion TCI of sufentanil can decrease BIS value further during propofol anesthesia.

Objective To investigate the protective effects of pretreatment with low-dose ketamine on intestinal mueosa against ischemia-reperfasion injury (I/R) and the underlying mechanism. Methods Forty-eight male SD rats weighing 230-270 g were randomly divided into 6 groups (n = 8 each) : group Ⅰ sham operation (S) ;group Ⅱ ketamine + sham operation (KS);group Ⅲ l/R;group Ⅳ ketamine + I/R (K);groupⅤ ketamine + ZnPPⅨ + I/R (KZ) and group Ⅵ ZnPPⅨ + I/R. Ketaminc 10 mg/kg and/or ZnPPⅨ 5 mg/kg were injected intraperitoneally 30 min before I/R in group Ⅳ, Ⅴ and Ⅵ. Intestinal I/R was produced by clamping of superior mesentery artery for 1 h followed by 6 h reperfusion. The animals were then killed and a segment of small intestine of 2 cm in length at about 10 cm from ileocecal valve was removed for determination of MDA content and SOD activity, HO-1 and iNOS expression and histological examination. The degree of intestinal tissue damage was graded using Chiu's scoring system (0 = normal, 5 = severe damage-exfoliation of villi, disruption of proper lamina, bleeding and ulceration). Results Intestinal MDA content was significantly increased, SOD activity was decreased and HO-1 and iNOS expression was significantly up-regulated by I/R (group Ⅲ) as compared with group Ⅰ and Ⅱ . Ketamine pretreatment significantly attenuated I/R-induced increase in MDA content and decrease in SOD activity and the protective effects of ketamine against I/R were counteracted by concomitant asministration of ZnPPⅨ. Microscopic examination showed that the pathological changes induced by I/R were significantly attenuated by ketamine and the protective effects of ketamine pretreatment against I/R were reversed by ZnPPⅨ in group Ⅴ. Conclusion Low-dose ketamine pretreatment can significantly ameliorate intestinal ischemia-reperfusion injury and up-regulation of intestinal HO-1 expression and down-regulation of iNOS are involved in the mechanism.

Objective To investigate the effects of repeated administrations of 6% hydroxyethy] starch (HES) 130/0.4 or 7.5 % NaCl (NS) on brain water content (BWC) after experimental intracerebral hemorrhage (ICH) in rats.Methods One hundred and sixty-seven male SD mrs weighing 260-300 g were randomly divided into 4 groups: group Ⅰ sham operation (S) (n = 20) ;group Ⅱ ICH (n = 38) ;group Ⅲ NS + ICH (n = 55) and group Ⅳ HES + 1CH (n = 54). The animals were anesthetized with intraperitoneal 10% chloral hydrate 400 mg/kg. Experimental ICH was produced by injection of fresh autologous blood 50 μl into right caudate nucleus. In group NS (group Ⅲ) 7.5% NaCl 5 ml/kg and in group HES (group Ⅳ) 6% HES 30 ml/kg were injected at 2, 24, 48 and 72 h after ICH. In group S and ICH (group Ⅰ and Ⅱ) 5 animals were killed at 2, 24, 48 and 72 h after ICH, while in group Ⅲ (NS) and Ⅳ (HES) 5 animals were killed at 2, 24, 48 and 72 h after ICH, immediately before and after NS/HES infusion for determination of ipsilateral and contralateral cerebral cortex and basal ganglion, weight and W/D weight ratio. Rosenberger behavior scores and survival rates were also recorded. Results In group Ⅲ (NS + ICH) and Ⅳ (HES + ICH) the water content of ipsilateral cerebral cortex and basal ganglion was significantly lower than in group Ⅱ (ICH). Rosenberger behavior scores at 24 h and 48 h after ICH were significantly lower in group NS and HES than in group Ⅱ (ICH) . The survival rates at 24, 48 and 72 h after ICH were significandy lower in group Ⅱ than in group NS and HES, especially at 72 h in group HES. Conclusion Repeated administrations of 6% HES 130/0.4 or 7.5% NaCl can ameliorate brain edema after ICH.

Objective To evaluate the effect of midazolam on platelet activation in patients with coronary heart disease (CHD) .Methods Brachial venous blood samples 5 ml drawn from 10 healthy adult volunteers and 40 patients with CHD were anticongulated with 3.8 % sodium citrate. Platelet rich plasma (PRP) 3 ml was obtained by centrifngation at 800 rpm for 8 min. Experiment Ⅰ : Ten portions of PRP from healthy adult volunteers served as control group with 1 ml for each (group ⅠC, n = 10). Forty portions of PRP from patients with CHD were randomly divided into 4 groups (n = 10 each): ⅠM0, ⅠM1,ⅠM2 and ⅠM3. In group ⅠC and ⅠM0, midazolam was not added while in group ⅠM1 , ⅠM2 and ⅠM3, midazolam was added with the final concentration at 100, 200 and 400 ng/ml respectively and the PRPs were then incubated for 3 min. The platelet aggregation rote was determined using turbidimetric method. Experiment Ⅱ : After the remaining PRP was eentrifnged at 2000 r/ rain for 5 min, washed platelets (WPs) were obtained. Ten portions of WPs from healthy adult volunteers served as control group with 1 ml for each (group ⅡC, n = 10). Forty portions of WPs from patients with CHD were randomly divided into 4 groups (n = 10 each) : ⅡM0, ⅡM1, ⅡM2 and ⅡM3· In group ⅡC and ⅡM0, midazolam was not added while in group Ⅱ, ⅡM2 and ⅡM3, midazolam was added with the final concentration at 100, 200 and 400 ng/ml respectively and the WPs were then incubated for 3 min. The content of platelet cAMP and were measured by enzyme immunoassay. Results Platelet aggregation rate was significantly higher in group ⅠM0 than in group ⅠC(P<0.01). Compared with groupⅠM0, platelet aggregation rate was significantly decreased in group ⅠM2 and ⅠM3(P<0.01) but there was no significant change in group ⅠM1 (P >0.05). The content of platelet cAMP was significantly decreased while the level of TXB2 was significantly increased in group ⅡM0 as compared with group ⅡC (P < 0.01). Compared with group Ⅱ M0, the content of platelet cAMP was significantly increased (P <0.05 or 0.01) while the level of TXB2 was significantly decreased in group ⅡM2 and ⅡM3(P< 0.01), but there was no significant change in group ⅡM1 (P > 0.05). Conclusion Midazolam 200 and 400 ng/ml can inhibit the platelet activation through increasing the content of platelet cAMP and reducing the production of TXA2 in vitro.

Objective To investigate the efficacy of pulse index continuous cardiac output (PICCO) monitoring in maintaining adequate blood volume in patients undergoing off-pump coronary artery bypass grafting (OP-CABG).Methods Forty-seven ASA Ⅰ-Ⅲ patients aged 43-64 yr weighing 50-85 kg undergoing OP-CABG were included in this study. Global end-diastolic volume (GEDV), extravascular lung water (EVLW), global end-diastolic volume index (GEDVI), MAP, cardiac output (CO) and cardiac index (CI) were monitored by using PICCO monitor before induction of anesthesia (baseline), at the end of operation and at 4 and 8 h after operation. Blood volume was maintained during operation by adjusting the volume and infusion rate of succinyl gelatin and lactated Ringer's solution according to volume indexes and hemodynamic indexes. GEDVI was maintained at 600-800 ml/m2 and Hct≥30% by transfusion of whole blood or erythrocyte suspension;MAP was maintained at 70-90 mm Hg by intravenous infusion of nitroglycerine (0.5-1.0 μg·kg-1·min-1) or diltiazem (2-6 μg·kg-1·min-1); HR was maintained at≤75 bpm by intravenous dopamine infusion (3-5 μg·kg-1·min-1). The oxygen delivery index(DO2 I) and oxygen consumption index (VO2 I) were calculated. Arterial blood samples were taken for blood gas analysis. Results The CI, DO2I and VO2I were increased at the end of operation, and at 4 h and 8 h after operation as compared with the baseline values before induction of anesthesia (P<0.05 or 0.01). Conclusion Perioperative blood volume can be well maintained with PICCO monitoring in patients undergoing off-pump coronary artery bypass grafting.

Objective To investigate the effect of ketamine pretreatment on acute tolerance to morphine in rats with chronic inflammatory pain.Methods Twenty-four adult male SD rats weighing 180-200 g were randomly divided into 3 groups (n=8 each): group Ⅰ morphine (M) ,group Ⅱ ketamine (K) and group Ⅲ ketamine + morphine (KM). Chronic inflammatory pain was induced by subcutaneous injection of Freund's adjuvant 0.125 ml into the plantar surface of left hindpaw. Three days after Freund's adjuvant injection, the animals received intraperitoneal (IP) morphine 5 mg/kg in group M, IP ketamine 10 mg/kg in group K or IP ketamine 10 mg/kg 10 min before IP morphine 5 mg/kg in group KM once a day for 3 consecutive days respectively. The paw withdrawal threshold to yon Frey hair stimulation (PWT) and paw withdrawal latency to noxious thermal stimulation(PWLT) using the hot plate test were measured before Freund's adjuvant injection (T0, baseline), and every day before (T1) and at 15 (T2), 30 (T3), 60 (T4) and 120 min (T5) after medication for 3 days (D1,2,3).Results PWT was significantly increased after medication on D1,2,3 in group KM but only on D1,2 in group M. PWLT was significantly prolonged after medication on D1,2,3 in group KM but only on D1 in group M. Conclusion Ketamine 10 mg/kg pretreatment can decrease the acute tolerance to morphine in rats with chronic inflammatory pain.

Objective To investigate the effects of angiotensinⅡ (AngⅡ) on the Apelin mRNA and APJ mRNA expression in pulmonary microvascular endothelial ceils (PMVECs) in rats. Methods Pulmonary microvascular endothelial ceils obtained from 24 h old neonatal SD rats were cultured in DMEM liquid culture medium. The 2nd-4th generation PMVECs were inoculated on 6-well plates (5×105). The experiment was performed in two parts. In part Ⅰ different concentration of AngⅡ 0, 10-9, 10-8, 10-7, 10-6mol/L (group Ⅰ- Ⅴ) were added into the PMVECs. The expression of Apelin mRNA and APJ mRNA was determined at 24 h after addition of Ang Ⅱ by RT-PCR. In part Ⅱ the cells were exposed to 10-7 mol/L Ang Ⅱ. The expression of Apelin mRNA and APJ mRNA was determined immediately and at 1, 6, 12, 24, 48 h(group Ⅰ-Ⅵ) after addition of Ang Ⅱ by RT-PCR. Results In part Ⅰ Apelin mRNA expression was significantly higher in group Ⅱ (Ang Ⅱ 10-9 mol/L) but lower in group Ⅲ-Ⅴ (AngⅡ 10-8, 10-7, 10-6 mol/L) than in group Ⅰ (control, Ang Ⅱ 0 mol/L). The APJ mRNA expression was significantly lowered in group Ⅱ-Ⅴ in a dose-dependent manner as compared with control group (group Ⅰ). In partⅡ beth Apelin mRNA and APJ mRNA expression exhibited a bi-phasic response to AngⅡ 10-7 mol/L, increased at first and was then decreasing with time. The Apelin mRNA and APJ mRNA expression reached the peak at 1 h of incubation with Ang Ⅱ respectively. Conclusion Ang Ⅱ decreases both Apelin mRNA and APJ mRNA expression in PMVECs in a dose and time dependent manner. The down-regulation of Apelin mRNA and APJ mRNA expression may be involved in the mechanism of injury to PMVECs.

Objective To investigate the effects of different body temperatures on the neuromuscular block induced by different doses of cisatracurium in rabbits. Methods Seventy-two healthy New Zealand white rabbits of both sexes weighing 2.0-2.2 kg were randomly divided into 3 groups (n=24 each): hypothermia group (L), normothermia group (N) and hyperthermia group (H). The rectal temperature was set at 34.5℃, 38.5℃ and 41.8℃ in group L, N and H respectively. Each group was further divided into 4 subgroups (n=6 each) receiving intravenous cisatracurinm 0.33, 0.66, 0.99 and 1.32 mg/kg respectively after rectal temperature was stabilized for 20 min. The animals were anesthetized with iv 20% methane 1 g/kg, tracheostomized and mechanically ventilated (VT 12 ml/kg, RR 60 bpm, I:E = 1:2;FiO2 100% ). TOF was monitored. The onset time, the duration of action (from the end of cisatracurium injection to the recovery of T1 to 5%, 25% and 95% of control height) and recovery index (recovery of T1 from 25% to 75% of control height) were recorded. MAP, HR and rectal temperature were recorded at 5 min before alteration of the body temperature, at 2 min before and 5, 10, 30, 60 and 90 min after administration of cisatracurium. Results (1) With the same dose of cisatracurium the onset time and duration of action were significantly shorter in group H, longer in group L and recovery from N-M block faster in group H, slower in group L as compared with group N. (2) At the same body temperature the onset time was significantly shortened and the duration of action and recovery were significantly prolonged as the dose of cisatracurium increased. (3) There was significant difference in the effect of interaction between different doses of cisatracurium and different temperatures on the onset time. (4) With the same dose of cisatracurium MAP was significantly decreased in group H, increased in group L, while HR was significantly increased in group H, decreased in group L. Conclusion The neuromuscular blocking effect of cisatracurium is decreased when the body temperature is increased and vice versa. The neuromuscular blocking effect of cisatracurium (0.33-1.32 mg/kg) is dose-dependent at the same body temperature. There is interaction between the two factors.