Objective To investigate the effect of different levels of propofol anesthesia on 5-HT metabolism in brain. Methods Forty Japanese Long-ear rabbits of both sexes, aged 8 months-2yr, weighing 2-3 kg were used for study. Anesthesia was induced and maintained with propofol administered by a TCI system. Blood propofol concentration required for different depths of anesthesia, as indicated by BIS monitoring and loss of chewing reflex (light anesthesia) and loss of response to tail nipped (deep anesthesia), was determined by high-performance liquid chromatography(HPLC) in 10 rabbits. Thirty rabbits were randomly divided into 3 groups often animals in each group: (1) control group received no propofol; (2) light anesthesia group and (3) deep anesthesia group. Different depths of propofol anesthesia were maintained for 1 h. At the end of one hour propofol anesthesia the animals were decapitated. Brain was immediately removed and cerebral cortex, hippocampus and thalamus were separated on ice. Their contents of 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by spectrophoto-fluorometer.Results 5-HT content of cerebral cortex was significantly increased after anesthesia. 5-HT content of hippocampus and 5-HIAA content of thalamus decreased significantly with increasing anesthetic depth. Conclusion Propofol improves 5-HT activity in cerebral cortex and thalamus and decreases 5-HT activity in hippocampus indicating that 5-HT metabolism may be involved in the mechanism of propofol anesthesia.

Objective To investigate the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the lung tissue in a rat model of ventilator-induced lung injury. Methods Thirty healthy male SD rats weighing 200-250g were randomly divided into 3 groups( n = 10 each) : group A spontaneous breathing; group B small tidal volume (VT = 7 ml?kg-1, RR = 40 bpm, FiO2=0.21) and group C large tidal volume (VT = 40 ml?kg-1, RR = 20 bpm, FiO2=0.21). The animals were mechanically ventilated for 4 h in group B and C. The lung injury was assessed by measurement of PaO2 /FiO2 . At the end of the experiment the animals were killed and the lungs were removed. The right lung was used for determination of the expression of mRNAs of MMP-2, MMP-9, TIMP-1 and TTMP-2 using RT-PCR and histologic examination. The left lung was weighed and then lavaged. The broncho-alveolar lavage fluid (BALF) was collected for total WBC and neutrophil counts and determination of total protein content and gelatinase activity. After lavage the left lung was heated at 60℃. The W/D lung weight ratio was calculated. Results PaO2/FiO2 was significantly lower after 4h mechanical ventilation in group C than in group A and B. The total WBC count and total protein content in BALF were significantly higher in group C than in group A and B. The W/D ratio of the left lung was significantly higher in group C than in group A and B. Microscopic examination showed that there were marked WBC infiltration and destructive changes of alveolar walls in group C. The levels of gelatinase (MMP-2 and MMP-9) activities in BALF were significantly higher in group C than in group A and B. The expression of the mRNA of MMP-2 and MMP-9 was significantly higher in group C than in group A and B, but there was no significant difference in the expression of the mRNA of TIMP-1 and TIMP-2 between group C and group A and B. Conclusion Large tidal volume ventilation can induce acute lung injury. MMP-2 and MMP-9 play an important role in the development of ventilator induced lung injury and the imbalance between MMPs and TIMPs contributes to the mechanism of ventilator-induced lung injury.

Objective To investigate the influence of thiopentone, midazolam, etomidate and propofol on the suxamethonium-induced serum potassium increase, muscle fasciculations and myalgia Methods Sixty patients, ASA class Ⅰ-Ⅱ were allocated randomly to receiving intravenous thiopentone 5mg/kg(thiopentone-group), midazolam 0.3mg/kg( midazolam-group), etomidate 0.3mg/kg(etomidate-group)or propofol 2mg/kg(propofol-group) respectively, followed by intravenous suxamethonium and tracheal intubation. Serum potassium concentration was measured before induction and intubation and after intubation. The incidences of muscle fasciculation during induction and postoperative mylgia were observed .Results As compared with that before induction ,the serum potassium levels in thiopentone- and etomidate-group increased significantly by 3.4% and 5.3% respectively after induction (P0.05).The incidences of muscle fasciculation and postoperative myalgia inmidazolam- and propofol -group were significantly lower than in thiopentone- and etomidate -group (P

Objective To investigate the antioxidative potential of propofol in adults undergoing open-heart surgery with cardiopulmonary bypass (CPB) Methods Thirty patients scheduled for cardiac procedures with CPB were selected Propofol (01 mg?kg -1?min -1, group A) or fentanyl (5?g?kg -1?min -1, group B) was administered to maintain anesthesia after aorta was cross-clamped Blood samples were drawn pre-anesthesia, pre-CPB, 30 min following CPB, at the end of CPB, 1h after CPB, at the end of operation, 12 and 24 h postoperatively RBC suspension was prepared to measure the erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) and phosphofructokinase (PFK) activities, total erythrocyte reduced glutathione (GSH) and oxidized GSH (GSSG) and GSH/GSSG ratio was calculatedResults In group A, G-6-PD and PFK activities and GSH/GSSG ratio remained unchanged significantly during CPB and postoperatively In group B, G-6-PD activity increased and PFK activity and GSH/GSSG ratio decreased significantly from 30th min of CPB to 12th h postoperativelyConclusions Propofol attenuates free radical activity during CPB to reduce the free radical-induced injury, while fentanyl has no effect on free radical reduction during CPB

Objective To evaluate the relationship between erythrocyte injury and intracellular calcium ion overload and the protective effect of propoful on erythrocytes during cardiopulmonary bypass(CPB) Methods Thirty children (male 21,female 9) with congential heart disease scheduled for elective open heart surgery with CPB were randomly divided into two groups : control group (C) and propoful group (P) The congential heart disease included ventricular septal defect (17 patients) and atrial septal defect (13 patients) The age ranged from 2 10 yr and body weight 10 35kg Anesthesia was induced with fentanyl 20 ?g/kg and vecuronime 0 1mg/kg in both groups and maintained with low concentration of isoflurane inhalation in group C and propofol intravenous infusion at a rate of 6mg?kg -1 ?h -1 in group P Blood samples were taken before and 20 min after CPB was began, at the end of CPB and 2 and 4h after CPB for determination of intracellular calcium ion content (E Ca 2+ ), Ca 2+ ,Mg 2+ ATPase and Na +, K + ATPase activities, erythrocyte filtration index(IF), mean corpuscular volume (MCV) and plasma free hemoglobin concentration (F Hb) Results In control group E Ca 2+ ,IF,MCV and F Hb gradually increased and Ca 2+ ,Mg 2+ ATPase and Na +,K + ATPase activities decreased during CPB The increase in E Ca 2+ was linearly paralleled to IF,MCV and F Hb There was no significant change in all the above mentioned parameters The difference in these parameters was significant between the two groups Conclusions The study suggests that erythrocyte injury is related to the increase in intracellular calcium ion during CPB and propoful has a protective effect on erythrocyte against injury due to its abilities to scavenge free radical and inhibit calcium channel

Objective To investigate the effects of hemo oxygenase-endogenous carbon monoxide (HO-CO) on mortality of septic shock in rats. Method Eighty healthy Sprague-Dawley rats were randomly divided into four groups (n=20) :group-C,group-Z, group-SS and group-LZ. MAP was monitored continuously,and deaths within 7 days were recorded. Evans blue in lung, ALT, AST, Cr and BUN in plasma, SOD and MDA in kidney, lung and liver,and HO-1 mRNA,HO-2 mRNA,HO-1 protein and HO-2 protein in kidney, lung, femoral artery and liver were measured.Data were analyzed usiny ANOVA. Results ① Mortality in group-SS was lower than that in group-LZ (P<0.05). ②MAP in group-LZ was greater than that in group-SS (P<0.05). ③ Plasma ALT, AST, Cr and BUN,and MDA contents of liver, kidney and lung, and Evans blue content of lung in group-SS were lower than those in group-LZ (P<0.05). Contrarily,the plasma levels of COHb and SOD activity in liver, kid-ney and lung in group-SS were greater than those in group-LZ (P<0.05). ④ HO-1 mRNA and HO-1 protein levels in liver, kidney, femoral artery and lung tissues in group-LZ were lower than those in group- SS (P<0.05). There were no significant difference in HO-2 rnRNA and HO-2 protein found between one another of four groups (P>0.05). Conclusions The up-regulation of HO-1 protein followed by increase CO can reduce the mortality during septic shock, while the hypotension, which is partly attributed to HO-1 protein and CO,matters little to mortality.

Objective To investigate the changes in the expression of Egr-1, C-jun and IL-1? mRNA and protein in the lung injured by mechanical ventilation. Methods Forty male SD rats weighing 250-320 g were randomly divided into 5 groups (n = 8 each): group A received no mechanical ventilation; group B-E received mechanical ventilaion for 30 (B), 60 (C), 90 (D) and 120 (E) minutes. The animals were anesthetized with intraperitoneal 3% pentobarbital 35 mg?kg-1 , tracheostomized and mechnically ventilated (VT =42 ml?kg-1 , RR = 40 bpm, I: E = 1:2, FiO2 = 21 % ) . Arterial blood samples were taken for blood gas analysis. The animals were killed at the end of mechanical ventilation in group B-E and after tracheostomy in group A. The lungs were removed for microscopic examination using HE staining. The expression of Egr-1, C-jun and IL-1? mRNA and protein was detected by RT-PCR and immuno-histochemical technique respectively. Results There was no significant difference in PaO2 and SaO2 among the 5 groups while PaCO2 was significantly decreased in group B and C but increased in group E as compared with group A. The expression of Egr-1, C-jun and IL-1? mRNA and protein was significantly increased by mechanical ventilation in a duration - dependent manner. Histological studies demonstrated that the damage to the lung was correlated with the duration of mechanical ventilation in terms of perivascular inflammatouy cell infiltration, exudates and hemorrhage in the alveoli and thickening of alveolar walls. Conclusion The results of our study show that mechanical ventilation activates and upregulates the expression of the early response genes in a duration - dependent manner. The upregulation of the expression of these genes might be involved in the underlying mechanism of lung damage induced by mechanical ventilation.

To investigate the effect of thiopental sodium on the release of glutamate and gamma-aminobutyric acid (GABA) from synaptosomes in the prefrontal cortex, synaptosomes were made, the spontaneous release and the evoked release by 30 mmol/L KCl or 20 micromol/L veratridine of glutamate and GABA were performed under various concentrations of thiopental sodium (10-300 micromol/L), glutamate and GABA concentrations were determined by reversed-phase high-performance liquid chromatography. Our results showed that spontaneous release and evoked release of glutamate were significantly inhibited by 30 micromol/L, 100 micromol/L and 300 micromol/L thiopental sodium, IC50 of thiopental sodium was 25.8 +/- 2.3 micromol/L for the spontaneous release, 23.4 +/- 2.4 micromol/L for KCl-evoked release, and 24.3 +/- 1.8 micromol/L for veratridine-evoked release. But GABA spontaneous release and evoked release were unaffected. The study showed that thiopental sodium with clinically related concentrations could inhibit the release of glutamate, but had no effect on the release of GABA from rats prefrontal cortical synaptosomes.
Glutamic Acid/*metabolism ; Hypnotics and Sedatives/pharmacology ; Prefrontal Cortex/*metabolism ; Rats, Sprague-Dawley ; Synaptosomes/*metabolism ; Thiopental/*pharmacology ; gamma-Aminobutyric Acid/*metabolism

BACKGROUND: As an important part of systemalimbica, hippocampus involves in emotion, perceiving and learning memory and can be affected by anesthesia.OBJECTIVE: With target controlled infusion of propofol, the depth of anesthesia was well controlled. And under anesthesia in various depths, cfos gene expressions in different regions of hippocampus in rabbits were detected to find the target site for central nervous inhibition by propofol.DESIGN :It was a randomized controlled study.SETTING:Department of Anesthesiology ,Shenzhen Second People's Hospital; Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiment was conducted in the Neurobiological Laboratory of Tongji Medical College, Huazhong University of Science and Technology from May 2000 to June 2001. Thirty Japanese white rabbits were selected and randomly divided into control group, light anesthesia group and deep anesthesia group, with 10 rabbits in each group.METHODS:Intravenous cannulas were placed in external jugular vein (EJV) and femoral artery in all animals. According to the propofol plasma concentration, the infusion of propofol and the depths of anesthesia were well controlled. In light anesthesia group, the plasma concentration of propofol was (9.28±0.12)mg/L. In deep anesthesia group, the plasma concentration of propofol was (11.63±0.29)mg/L. Thirty minutes after being anesthetized, the animals in the two experimental groups were decapitated and the animals in control group were killed by air embolism through ear vein. Coronal sections were sliced continuously, in thickness of 7μm and 1 slice in 100 μm tissue was selected. In situ hybridization was performed to detect the c-f os mRNA in Area CA1, CA3 and dentate gyrus of the hippocampus. In each rabbit, 5 sections were selected randomly.Under a light microscope, photos were taken in 15-20 fields. And then average absorbency and average grayscale were calculated. The grayscale scores were classified as 256 scales. A lower grayscale score indicated a higher positive rate.MAIN OUTCOME MEASURES: ①Under various depths of anesthesia,in situ hybridization results of Area CA1, CA2 and dentate gyrus of the anesthesia, average grayscale scores of Area CA1, CA2 and dentate gyrus of the hippocampus in rabbits were assessed.② Under various depths of anesthesia, average grayscale scores of Area CA1, CA2 and dentate gyrus of the hippocampus in rabbits were calculated.RESULTS:Thirty rabbits entered the statistical analysis procedure.①Under various depths of anesthesia, in situ hybridization results of Area CA1 of the hippocampus in rabbits: In control group, brown, sparse or dense, light-stained or deep-stained c-fos positive cells could be observed. In light anesthesia group, dense, moderately stained c-fospositive neurons could be observed. In deep anesthesia group, cells were denser with deeper stained cytoplasma. ② Under various depths of anesthesia, in situ hybridization results of dentate gyrus of the hippocampus in rabbits: In light anesthesia group, positive cells were strongly stained in deep brown with transparent and vacuolar nuclei. In deep anesthesia group, a large number of c-fos positive cells in great dense could be observed. ③Under various depths of anesthesia, grayscale scores of different regions of the hippocampus in rabbits: Compared with control group, grayscale scores of Area CA1 and dentate gyrus of the hippocampus were significantly decreased in both light and deep anesthesia groups [(168±5), (80±7), (59±5)% ,P ＜ 0.05; (163±8),(103±15), (67±6)%,P ＜ 0.05,P ＜ 0.01]. This was more significant in deep anesthesia group than in light anesthesia group (P ＜ 0.01 ). For Area CA3, the grayscale scores in each group were similar.CONCLUSION: ①With the increasing depth of propofol anesthesia, c-fos gene expression is increased in hippocampus in rabbits. ② After anesthesia, the average grayscale score of Area CA1 and dentate gyrus of the hippocampus are significantly decreased, and this is more significant after deep anesthesia. However, there is no significant change in Area CA3. This indicates that the central inhibitory receptor sites of propofol are various in different brain regions, which supposes that the Area CA3 is not the central receptor sites of propofol.

Aim To investigate the effect of thiopental sodium on the release of glutamate and GABA from synaptosomes of rats prefrontal cortex. Methods Synaptosomes were made from rats prefrontal cortex and incubated with artificial cerebral and spinal fluid (aCSF), then divided into five groups: group base release (Base), group thiopental sodium 10 ?mol?L -1 (THS 10), group thiopental sodium 30 ?mol?L -1 (THS 30), group thiopen tal sodium 100 ?mol?L -1 (THS 100) and group thiopental sodium 300 ?mol? L -1 (THS 300). Various concentrations of thiopental sodium were added to aC SF, the release of glutamate and GABA were performed under 37℃ and measured using reversed-phase high-performance liquid chromatography (RP-HPLC). When Ca 2+-independent release of glutamate and GABA were studied, Ca 2+ was omitted from aCSF.Results Compared with Base, thiopental sodium 30 , 100 and 300 ?mol?L -1 inhibited Ca 2+-dependent release of gluta mate evoked by KCl or veratridine significantly (P