BACKGROUND: The disorder of energy metabolism and cerebral edema after cerebral ischemia-reperfusion are the important factors to inducecerebral ischemia-reperfusion injury. The Chinese herb, breviscapine, whose effective component is scutellarin, can prevent the activation of protein kinase C evoked by ischemia-reperfusion, relieve calcic overload and reduce the volume of ischemia infarcted focus volume, and then alleviate cerebral ischemia-reperfusion injury. But what are the influences of breviscapine on energy metabolism and cerebral edema after cerebral ischemia-reperfusion?OBJECTIVE: To observe the effects of breviscapine parenteral solution on energy metabolism and cerebral edema after cerebral ischemia-reperfusion in gerbils.DESIGN: A randomized control trial.SETTING: Affiliated Hospital of Jining Medical College, Jiangsu Provincial Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical College.MATERIALS: The experiment was carried out in the Jiangsu Provincial Key Laboratory of Anesthesiology Between February and August 1999. Seventy-two male gerbils were used.METHODS: The gerbils were randomly divided into sham-operated group (n=8), normothermia control group (n=32) and breviscapine group (n=32).According to the reperfused time, the normothermia control group and breviscapine group were divided into 4 subgroups with 8 gerbils in each subgroup: 0, 10, 30 and 60-minute reperfusion groups. The gerbils in the normothermia control group and breviscapine group were made into models of forebrain ischemia reperfusion, treated with ischemia for 10 minutes. In the sham-operated group, only bilateral common carotid arteries were freed but not occluded. In the breviscapine group, the gerbils were given intraperitoneal injection of breviscapine psrenteral solution (90 mg/kg) at 15 minutes before ischemia. The gerbils in the sham-operated group and normothermia control group were treated with saline of the same volume. The brain water was determined by drying electrothermostat. The contents of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine phosphate (AMP) in hippocampus were determined with high performance liquid chromatography and ultraviolet detector.MAIN OUTCOME MEASURES: ① ATP, ADP and AMP contents in hippocampus; ② Water contents in cerebral cortex.RESULTS: All the 72 gerbils were involved in the analysis of results without deletion. ① ATP, ADP and AMP contents in hippocampus: At 0, 10, 30 and 60 minutes after reperfusion, ATP and adenine nucleotide pool contents in hippocampal tissue in the normothermia control group were obviously decreased, the ATP contents were 68%, 56%, 49% and 50% of those in the sham-operated group respectively (P ＜ 0.01), and adenine nucleotide pool contents were 62%, 50%, 51% and 52% of those in the sham-operated group respectively (P ＜ 0.01). The ATP contents at each time point in the breviscapine group were 84%, 69%, 64% and 63% of those in the sham-operated group respectively, and the adenine nucleotide pool contents were 86%, 72%, 68% and 69% of those in the sham-operated group respectively, which were all obviously higher than those in the normothermia control group (P ＜ 0.05). ②Water contents in cerebral cortex: The water content after cerebral ischemia-reperfusion in the normothermia control group was obviously higher than that in the sham-operated group, and gradually aggravated with the prolongation of reperfusion. The water content in the breviscapine group was obviously higher than that in the sham-operated group, but markedly lower than that in the normothermia control group (P ＜ 0.05).CONCLUSION: Breviscapine can play a role in protecting brain through inhibiting disorder of energy metabolism and relieving cerebral edema.

BACKGROUND: Pyramidal cells in hippocampal CA1 region are neurons most susceptible to ischemia-hypoxia damage. Their membrane potential is shown as hyperpolarization of cell membrane during early hypoxia. With the progress of hypoxia time, cell membrane has slow and rapid hyperpolarization, which causes irreversible damage to neurons.OBJECTIVE: To investigate the effects of the blocker of N-methyl-D-aspartate receptor MK801 on the electrophysiological changes of CA1 neurons during hypoxia in isolated hippocampal slices of rats with intracellular recording technique.DESIGN: Observational and controlled study.SETTING: The 97th Hospital of the Chinese PLA, Provincial Key Anesthesiology Laboratory of Xuzhou Medical College; Center of Health Science, State University of New York.MATERIALS: The experiment was conducted from September 2002 to March 2003 in the State University of New York. Five adult male SD rats were anesthetized with 0.02 volume of isoflurane after 3 minutes' pre-oxygenation with oxygen.METHODS: The hippocampal slices from the rats were randomly divided into simple anoxia group (n=10) and MK801 group (n=10). The slices in simple anoxia group were only subjected to 10-minute hypoxia with the artificial cerebrospinal fluid (ACSF), and the slices in MK801 group were treated with 100 μmol/L MK801 for 10 minutes before and during 10 minutes of hypoxia. The neuronal membrane potential before hypoxia, the rate of slow depolarization, the amplitude of and time to rapid depolarization were recorded with intracellular recording technique described in the literature. Meanwhile, the neuronal response to the intracellular current injection and Schaffer collateral stimulation were observed respectively at the end of 60 minutes' re-oxygenation.gion of hippocampal slices: It was significantly higher in simple anoxia group than in MK801 group [(0.20±0.05) mV/s, (0.08±0.03) mV/s, P ＜ 0.05].hippocampal slices: It was significantly higher in MK801 group than in of rapid depolarization of pyramidal cells in CA1 region of hippocampal slices: It was significantly lower in MK801 group than in simple anoxia sponse to stimuli was recovered in 9 out of 10 neurons.CONCLUSION: MK801 blocker of N-methyl-D-aspartate receptor can decrease the rate of slow depolarization of neurons induced by hypoxia, postpone the onset of rapid depolarization of neurons, and decrease the amplitude of rapid depolarization of neurons. This suggests that the blocker of N-methyl-D-aspartate receptor can relieve the hypoxic damage to neurons and promote the functional recovery of neurons.

Objective To investigate the role of microglial activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) .Methods Seventy-two male SD rats weighing 200-250 g in which intrathecal (IT) catheter was successfully inserted were randomly divided into 3 groups ( n = 24 each) : group sham operation; group SMIR and group SMIR + FT minocycline (a specific microglia inhibitor) . The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters. Pain behavior was assessed by paw mechanical withdrawal threshold ( MWT) to von Frey filament stimulation at 1 day before (T0,baseline) and 3, 7, 12, 22 and 32 days after operation (T1-5,) . Four animals were sacrificed at each time point in each group for detection of the expression of Iba-1 (a specific marker of microglia) in the spinal dorsal horn by immunofluorescence and the microglia was counted. Results MWT was significantly decreasedat T1-4, while the expression of Iba-1 and microglia counts in the spinal dorsal horn were significantly increased at T1, 2 by SMIR in group Ⅱ. IT minocycline significantly attenuated the hyperalgesia induced by SMIR at T1-4 and decreased Iba-1 expression and microglia counts at T1,2 in group Ⅲ. Conclusion Microglial activation in the spinal cord plays an important role in the development and maintenance of SMIR-evoked persistent postoperative pain in rats.

Objective To investigate the role of gamma-aminobutyric acid transporter-1 (GAT-1) in the spinal cord in a rat model of bone cancer pain.Methods Eighty female SD rats weighing 150-180 g were randomly divided into 5 groups (n =16 each): sham operation group(group Ⅰ ),bone cancer pain group(group Ⅲ ),sham operation+ NO-711 group(group Ⅲ ),Ⅳ group BCP + NO-711 group(group Ⅳ ) and BCP + vehicle group (group Ⅴ ).Bone cancer pain was induced by inoculating Walker-256 mammary gland carcinoma cells into medullary cavity of tibia.NO-711 (20 μg,10 μl) was administered intrathecally once a day for 3 consecutive days from the 14th day after operation.Mechanical withdrawl threshold (MWT) of mechanical stimulus was determined the day before operation and at days 3,5,7,10,14 and 16 after operation.The animals were sacrificed on the 16th day after operation,and then the spinal cords were removed for determination of the expression of GAT-1 and double immunostaining of GAT-1 and glial fibrillary acidic protein (GFAP,astrocyte marker).Results MWT were significantly decreased in groups Ⅱ,Ⅳ and Ⅴ as compared with groups.Ⅰ and Ⅲ.The expression of GAT-1 significantly up-regulated in groups Ⅱ,Ⅴ as compared with groups Ⅰ and Ⅲ.NO-711 significantly increased MWT,while decreased the expression of GAT-1 in group Ⅳ compared with groups Ⅱ and Ⅴ.The expression of GAT-1 up-regulation appeared colocalizes with in astrocytes activation in spinal dorsal horn.Conclusion The up-regulation of expression of GAT-1 in spinal cord is involued in the development and maintenance of bone cancer pain,which may be related to the astrocytes activation.

Objective To investigate the effect of intrathecal γ-aminobutyric acid transporter-1 ( GAT-1 )small interfering RNA (siRNA) on neuropathic pain in rats. Methods Male SD rats weighing 200-250 g were studied. The experiment was performed in 3 parts. Part Ⅰ Twenty rats were randomly divided into 5 groups ( n =4 each): GAT-1 siRNA-1 group, GAT-1 siRNA-2 group, GAT-1 siRNA-3 group, negative control siRNA group and DEPC treatment group. Two days after ligation of sciatic nerve, intrathecal siRNA 2 μg or equal volume of DF-PC was injected once a day for 3 consecutive days. The rats were killed and the lumbar segment of the spinal cord was removed at 2nd day after the last intrathecal injection for determination of the expression of GAT-1 in the spinal dorsal horn by Western Blot. Part Ⅱ Thirty rats were randomly divided into 3 groups ( n = 10 each): GAT-1 siRNA-3 + lipo2000 group, GAT-1 siRNA-3 mismatch siRNA + lipo2000 group, and DEPC treatment + lipo2000group. Paw-withdrawl threshold (PWT) to thermal and mechanical stimulation was measured before ligation of sciatic nerve, 3 days after ligation of sciatic nerve and at 1, 3, 5, 7 and 10 days after consecutive administration for 3 days. Part Ⅲ Eighty-four rats were randomly divided into 3 groups as described in Part Ⅱ ( n = 28 each). Four rats were killed at each time point and the lumbar segment of the spinal cord was removed for determination of the expression of GAT-1 in the spinal dorsal horn by Western blot. Results PWT to thermal and mechanical stimulation was significantly inreased and the GAT-1 expression was down-regulated after the injection of GAT-1 siRNA.Conclusion Intrathecal GAT-1 siRNA can reduce the neuropathic pain by inhibiton of up-regulation of the GAT-1 expression in the spinal dorsal horn in rats.

Objective To investigate the glial activation in the spinal cord in a rat model of persistent postoperative pain. Methods Forty-eight adult male SD rats weighing 200-250 g were randomly divided into 2 groups ( n = 24 each): group Ⅰ sham operation (group S) and group Ⅱ persistent postoperative pain. Persistent postoperative pain was evoked by skin/muscle incision and retraction (SMIR) as described by Flatters. Pawwithdrawal threshold to yon Frey hair stimulation was measured before operation (baseline) and at 1, 3, 12, 22and 32 d after establishment of the model. Four animals were sacrificed at each time point and lumbar segment of the spinal cord was removed for determination of expression of glial fibrillary acidic protein (GFAP) in the astrocytes by immunofluorescence histo-chemistry assay. Results The mechanical threshold started to decrease at 1 d after establishment of the model, and peaked at 12 d after establishment of the mode. Immunofluorescence histochemistry assay demonstrated that GFAP expression in the dorsal horn was significantly increased at 3 d after estabhshment of the model and reached the peak at 12 d and was maintained at the high level until 22 d after establishment of the model. Conclusion Glial activation is involved in the mechanism of persistent postoperative pain evoked by SMIR.

Aim To investigate the protective effect of different concentrations of isoflurane preconditioning in isolated rat hearts and the relationship between this effect with changes of endogenous antioxidant enzymes.Methods The isolated SD rat hearts perfused on Langendorff apparatus were randomly divided into 6 groups(n=14):control group(CON);1.44 MAC isoflurane control group(ISO);ischemia-reperfusion group(I/R);3 isoflurane preconditioning groups(I1,I2,I3).All hearts were made globally ischemic for 30 min followed by 60 min reperfusion except CON and ISO.The hearts of ISO and I1,I2,I3 were perfused with K-H solution saturated with 0.72 MAC or 1.08 MAC or 1.44 MAC isoflurane respectively for 20 min followed by 5 min washout after equilibrium.The cardiac function variables were measured after equilibrium,immediately before ischemia,at the end of 30 min and 60 min reperfusion.The infarct size and activities of the endogenous antioxidant enzymes were measured at the end of reperfusion.And the activities of enzymes in I2 group were measured after equilibrium,immediately before ischemia,immediately after ischemia and at the end of 30 min reperfusion.Results Ischemia/reperfusion significantly increased LVEDP and decreased LVDP,dp/dtmax,dp/dtmin and HR(P

Objective To study the changes in oxygen consumption ( VO2 ) and oxygen cost of breathing(OCB) in postoperative patients and the effects of various kinds of assisted ventilatory support on OCB.Methods Twenty patients (13 male, 7 female), aged 43-70 years, undergoing thoracic surgery were divided into two groups: (A) pulmonary disease(PD) group in which patients had chronic pulmonary disease and abnormal pulmonary function( n = 10); non-pulmonary disease (NPD) group in which patients had no chronic pulmonary disease and their pulmonary function was normal ( n = 10). Operation were performed under combined intravenous-inhalation anesthesia or general-epidural anesthesia. Metabolism of the patients was measured before anesthesia. After operation the patients were mechanically ventilated in ICU and PaCO2 was maintained between 4.6-6.0 kPa. Metabolism was measured 12h after operation when anesthesia had worn off, the patients were fully awake and breathing spontaneously. Their hemodynamics was stable. Body temperature was maintained at 37℃?0.5℃ . VO2 was measured using indirect colorimetry (Datex Deltatrac MBM-200). VO2, VCO2, energy expenditure(EE) and respiratory quotient (RQ) were recorded every minute for 30 min. OCB was calculated by deducting VO2 measured during controlled ventilation from VO2 measured during spontaneous breathing( OCB = VO2 spontaneous breathing - VO2 controlled ventilation) and expressed by OCB/VO2 spontaneous breathing ( % ) . During mechanical ventilation FiO2 was set

0.05);in contrast, intrathecal NMDA 2.5,5,10 ng could significantly and dose dependently decrease the HPPT(P