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

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

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.

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 evaluate the effects of penehyclidine hydrochloride (PHC) on the expression of Toll like receptor-4 (TLR4) and nuclear factor kappa B (NF-κcB) in a rat model of sepsis-induced acute lung injury (ALI).Methods Seventy-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =24 each) using a random number table:shame operation group (group S),ALI group and PHC group.Sepsis-induced ALl was induced by cecal ligation and puncture in anesthetized rats.In group PHC,PHC 0.45 mg/kg was intramuscularly injected immediately after cecal ligation and puncture.At 6,12,24 and 36 h after ligation,the broncho-alveolar lavage fluid (BALF) was collected for detection of TNF-α and IL-6 concentrations and the lungs were removed for determination of the expression of TLR4 (using RT-PCR and Western blot) and NF-κBp65 (using Western blot) in lung tissues and for microscopic examination.The pathological changes of lungs were scored.The wet to dry lung weight (W/D) ratio was calculated and the activity of myeloperoxidase (MPO) in lung tissues was measured.Results As compared with S group,the IL-6 concentrations in BALF at 6,12 and 24 h after ligation,TNF-α concentration in BALF at 6 and 12 h after ligation,and the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly increased in ALI group (P ＜ 0.05).Compared with ALI group,the TNF-α concentration in BALF at 6 and 12 h after ligation,and IL-6 concentrations in BALF,the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly decreased in group PHC (P ＜ 0.05).Conclusion PHC inhibits NF-κB activation and decreases inflammatory responses through blocking TLR4 expression in lung tissues,thus attenuating sepsis-induced ALI in rats.

Objective To investigate the protective role of losartan,an angiotensin Ⅱ receptor(AT1 type)blocker,in the mechanical ventilation-induced lung injury(VILI).Methods Forty Sprague-Dawley rats weighing 300-350 g were randomly divided into the following four experimental groups(10 rats in each group):control group(group A),normal tidal volume venti-lation group(group B),large tidal volume mechanical ventilation group(group C),large tidal volume mechanical ventilation plus Losartan pretreatment group(group D).The pulmonary tissues were removed for pathological examination and detection of NF-κB activity,and the lung lavage fluid was collected for analysis of white blood cell count,total protein concentration and the level of MIP-2,after the rats were sacrificed.Results The pathology of lung tissues was normal in groups A and B.There was obvi-ous inflammatory damage in lung tissues in group C.The pathological inj uries of lung tissue were significantly reduced in group D compared with group C.The NF-κB activity and the level of p65 were significantly higher in group C than in groups A and B (P<0.01);they were significantly reduced in group D compared with group C(P<0.05).Total protein concentration,the MIP-2 level and the white blood cell count were significantly higher in group C than in groups A and B(P<0.01).They were significantly reduced in group D compared with group C(P<0.05 or 0.01).Conclusion Losartan,a selective inhibitor of sub-type AT1 receptors for angiotensin Ⅱ,can relieve VILI by inhibiting the activity of NF-κB.