BACKGROUND: Both abnormal permeability of ionic channel and disturbance of ionic balance between inside and outside nerve cell are key factors for ischemic brain injury after ischemia. Depolarization induced by activation of sodium channel is starting link for cerebral ischemic injury.OBJECTIVE: To study the effects of droperidol on persistent sodium channel currents of pyramidal cell in hippocampal CA1 area of rats with cerebral ischemia with patch clamp technique so as to analyze whether droperidol can protect cerebral ischemic injury.DESIGN: Randomized controlled animal study.SETTING: Department of Anesthesiology of the Sixth People's Hospital Affiliated to Shanghai Jiaotong University and Department of Anesthesiology of the First People's Hospital Affiliated to Shanghai Jiaotong University.MATERIALS: The experiment was carried out at the Department of Anesthesiology of the First People's Hospital Affiliated to Shanghai Jiaotong University from April 2002 to April 2003. Totally 14 SD rats, aging 10-14days, without ablactation, were selected. Two cells in hippocampal CA1area of each rat were collected, totally 28 cells were divided into 4 groups:ischemic control group, 3 μmol/L droperidol group, 10 μmol/L droperidol group and 30 μmol/L droperidol group, with 7 cells in each group.METHODS: Pyramidal cells in hippocampal CA1 area were separated with digested enzyme method, and ischemic model of neuron was established through hypoxia and no sugar method. Cells were selected with the following conclusion criteria: well adherent wall, triangle or starry shape,bright soma, well refraction, obvious apophysis, steady plasma, and transparent nucleolus. Y-tube system was used for rapid medication. 3, 10 and 30 μmol/L droperidol were given to rats in 3, 10 and 30 μmol/L droperidols respectively, but rats in ischemic control group were not given any medicine. Whole-cell patch-clamp was used to recorded basic value of persistent sodium currents and changes of sodium channel currents during 3-minute and 5-minute ischemia.MAIN OUTCOME MEASURES: ① Record of normal persistent sodium current of neuron in cerebral hippocampal CA1 area; ② Record of persistent sodium current of neuron in cerebral hippocampal CA1 area during cerebral ischemia; ③ Effect of droperidol in various concentrations on persistent sodium current of neuron in cerebral hippocampal CA1 area during cerebral ischemia.RESULTS: Totally 28 cells in cerebral hippocampal CA1 area of 14 rats were entered the final analysis. ① Record of normal persistent sodium current of neuron in cerebral hippocampal CA1 area: 0.5 mmol/L CdCl2 calcium channel blocking agent and 20 mmol/L TEA kalium channel blocking agent were used to perform 400 ms square-wave stimulation under -105 mV claw voltage and -30 mV stimulated voltage. Introversion current,slight, late activation and lasting for a long time, was recorded and deter mined as persistent sodium currents by blocking toxin of puffer fish. ② Record of persistent sodium current of neuron in cerebral hippocampal CA1 area during cerebral ischemia: After 3-minute ischemia, persistent sodium currents in ischemic control group was increased as (1.60±0.21) times as that in normal group, and was (2.87 ±0.45) times after 5-minute ischemia. The difference was significant (P ＜ 0.05). ③ Effect of droperidol at various concentrations on persistent sodium current of neuron in cerebral hippocampal CA1 area during cerebral ischemia: Basic values of persistent sodium currents were (77.42±15.17) pA, (87.44±21.56) pA, (84.13±20.06) pA and (80.22±19.30) pA in ischemic control, 3, 10 and 30 μmol/L droperidol groups respectively, and the differences among groups were not significant. After 5-minute ischemia, values of persistent sodium currents were (105.36±17.16) pA, (94.74±18.88) pA and (84.88±13.94) pA in 3, 10 and 30 μmol/L droperidol groups respectively, which were obviously lower than that in the ischemic control group (218.31±29.34) pA.CONCLUSION: Persistent sodium currents increase under -105 mV claw voltage and -30 mV stimulated voltage during cerebral ischemic injury. Droperi dol can protect neuron by inhibiting the increase of persistent sodium current.

Aim Expressing muscle acetylcholin e receptors in mammallian cells using receptor clone technique.Methods The cDNA coding for the ?,?,?, ?,?-subunits of the mouse muscle nAC hR in pSP65, pSP64,pBS SK(-) are subcloned into pcDNA3.1+ by gene recobinant technique and then transfect HEK293 cells using lipofection technique.The ?-n AChR and ?-nAChR are transiently expressed in HEK293 cells membrane. Recording the response of transfected HEK293 cells to acetylcholine by using the whole- cell clamp technique.Results Transfected HEK293 cells may produ ce a inward current as appling acetylcholine.The current values are acctylcholin e-concentration-dependent.Conclusion ?-nAChR or ?-nAChR i s expressed successfully in HEK293 cells.

OBJECTIVETo study the pharmacodynamics of vecuronium,atracurium, mivacurium and rocuronium in patients with end-stage renal failure.

METHODSForty-six patients with end-stage renal failure scheduled for renal transplantation and 53 patients with normal renal function were given either vecuronium, atracurium, mivacurium or rocuronium. The neuromuscular effects were monitored by the evoked response of the adductor pollicis to train-of-four stimulation of the ulnar nerve.

RESULTSOnset of vecuronium, atracurium and mivacurium occurred faster or tended to be faster in patients with end-stage renal failure, but there was no significant difference in onset by rocuronium between the control patients and renal failure patients. Furthermore, the no-response period, duration of action and recovery of atracurium did not differ between the two groups. There was no significant difference in duration of action or recovery of mivacurium between the two groups, whereas its no-response period was significantly prolonged in the patients with end-stage renal failure. There was no difference in no-response period or duration of action after the initial dose of vecuronium or rocuronium between the two groups. However, no-response period and duration of effect by vecuronium and rocuronium were prolonged with increasing incremental doses in patients with end-stage renal failure.

CONCLUSIONSAll four muscle relaxants could be safely used in patients with end-stage renal failure. Onset of the relaxants were, in some cases, accelerated and no-response period of mivacurium was prolonged in patients with end-stage renal failure undergoing dialysis therapy. End-stage renal failure prolonged the no-response period and duration of action of vecuronium and rocuronium after repeated incremental doses, but did not alter those attributed to atracurium.

Adult ; Androstanols ; pharmacology ; Anesthesia, General ; Atracurium ; pharmacology ; Female ; Humans ; Isoquinolines ; pharmacology ; Kidney Transplantation ; Male ; Middle Aged ; Neuromuscular Blocking Agents ; pharmacology ; Succinylcholine ; pharmacology ; Time Factors ; Vecuronium Bromide ; pharmacology

Purpose To investigate the effects of different concentration of ketamine on Ca2 transsarcolemmalinflux induced by KCl in isolated rat ventricular myocytes. Methods Freshly isolated rat ventricular nyoeyteswere loaded with Fluo-3AM, a Ca2 + indicator. The effects of different concentration ketamine( 1 × 10- s, 1 × 10- 4,1 × 10-3 mmol/L) on the change of intracellular Ca2+ concentration induced by KCl were investigated. ResultsLow concentration ketamine(1 × 10-5 mrnol/L) did not change Ca2+ transsarcolemmal influx. Although mediumeoncentration ketamine( 1 × 10-4 rmol/L) made the influx slower, the eventual peak concentration of intracellularCa2+ had no difference from that of the control group. The high concentration ketamine (1 × 10-3 mmol/L) inhibited Ca2-1 influx,intracellular Ca2+ fluorescent intensity decreased about 13.2% (P＜0.05). ConclusionsKetamine inhibits Ca2 + trranssarcolemmal influx in isolated rat ventricular myocytes dosedependently, which may inpart explain its negative inotropic effect.

Aim The effects of diazepam on the whole cell sodium currents in rat sympathetic ganglion neurons were studied to investigate the mechanisms by diazepam mediates hypotension. Methods Whole cell patch clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic ganglion neurons. Results Diazepam dose dependently blocked the whole cell sodium currents. Under a V t of 0 mV and a V h of 80 mV 0.3 ?mol?L -1 diazepam reduced sodium peak currents by 14.76 %(P

AIM: To study the interactions of propofol and midazolam on the whole cell sodium channel currents in rat sympathetic ganglion neurons. METHODS: Whole cell patch clamp recordings were made from enzymatically isolated rat (7- 10 d ) superior cervical sympathetic ganglion neurons. Isobolographic analysis was applied to evaluate the potency of combinations of propofol and midazolam on Na + channel currents. RESULTS: Under V h= 80 mV and V t= 0 mV . Propofol and midazolam dose dependently blocked Na + currents with a mean drug concentration required to produce 50% current inhibition (IC 50 ): 33.12 ?mol?L -1 and 18.35 ?mol?L -1 ; clinically relevant concentrations of propofol and midazolam reduced Na + peak currents by 27.66 % (P

AIM: To explore the influence of different concentration midazolam on the macroscopic voltage gated potassium currents and to discuss the relationship between potassium currents and inhibitory effect of clinical relevant concentration midazolam on sympathetic nervous system. METHODS: Superior sympathetic ganglion neurons were dissociated enzymatically from 7 to10 day old rat. Experiments were performed about 5 h after plating at room temperature (20- 24 ℃ ). Appropriate solution was chosen to separate the K + current from the other transmembrane currents. 1 ?mol?L -1 TTX was applied to the extracelluar solution to block the Na + current. Midazolam was also resolved in extracelluar solution to get various concentration ( 0.1 , 0.3 ,3,10,50,100 ?mol?L -1 ). Currents were recorded with the patch clamp technique in whole cell configuration using glass electrodes with a tip resistance of 2- 4 M . Potassium currents were evoked by test pulse from -100 mV to +30 mV with holding potential -80mV. Data were analyzed using Clampfit 6.0 and Oringih 5.0 software. Whole cell current records were corrected for leakage and capacitance by using the P/5 protocol. RESULTS: Midazolam dose dependently inhibited the whole cell potassium currents. Clinical relevant concentration midazolam ( 0.3 ?mol?L -1 ) only reduced the peak currents by 3.89 %(P= 0.88 ). The concentration required to produce 50% current inhibition(IC 50 ) was 76.065 ?mol?L -1 . CONCLUSION: Midazolam inhibits the whole cell potassium current significantly and dose dependently, but clinical relevant concentration midazolam has minor effect on the potassium currents, indicating that the inhibitory effect of midazolam on potassium current is not related to the suppression of activity of sympathetic system.

AIM: To study the effects of droperidol on the enhancement of persistent sodium currents induced by in vitro ischemia-like condition in isolated rat CA1 paramidal neurons. METHODS: Whole-cell patch-clamp recordings were made from enzymatically isolated rat CA1 hippocampal paramidal neurons. Ischemia was induced by oxygen and glucose deprivation. RESULTS: All of 3, 10 ,and 30 ?mol?L -1 of droperidol significantly inhibited the enhancement of persistent sodium currents induced by ischemia, but the different concentrations did not show significant difference. CONCLUSION: Droperidol in clinical concentration can inhibit the enhancement of persistent sodium current induced by ischemia.

Objective To evaluate the feasibility of using auditory evoked potential index(AAI) to monitor the depth of nitrous oxide anesthesia. Methods Sixteen ASAⅠ-Ⅱpatients aged 23-64 years, weighing 51-86 kg scheduled for elective surgery under general anesthesia were studied. Patients with psychoneural diseases and hearing disturbances were excluded. The patients were premedicated with phenobarbital sodium 0.1g and atropine 0.5mg. AAI, BIS, 95% SEF, BP, HR, SpO2 monitoring were started before induction of anesthesia. The patients were preoxygenated for 5 min using a close-fitting face mask and 100% O2 at l0L?min-1 . Inhalation of nitrous oxide was then started. Nitrous oxide concentration was gradually increased in increments of 10% from 0% to 70% . AAI, BIS and 95%SEF were recorded and observer's assessment of alertness/sedation (OAA/S) scores were measured at each 10% increment of end-tidal nitrous oxide concentration which was maintained for 5 min. The correlation between AAI, BIS, 95% SEF and OAA/S scores was analyzed. Results OAA/S scores and AAI decreased as the nitrous oxide concentration increased. AAI correlated closely with OAA/S scores and end-tidal nitrous oxide concentration (the coefficients of Spearman' s rank correlation ? = - 0.739, 0.837, P