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BACKGROUND: It is indistinct that whether ketamine can exert antinociceptive effect througb influencing the transmission of nocuous information in spinal cord; Nitric oxide (NO) in spinal cord participates mainly in the formation and development of hyperalgesia, and it can also induce Fos protein expression. It is still controversal whether it contributes to the transmission and mediation of ketamine to pain signal.OBJECTIVE: To observe the response to formalin stimulation in spinal cord of the rats and the effect of ketamine.DESIGN: Balanced randomized animal trial.SETTING: Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College; Jiangsu Provincial Key Laboratory of Anesthesiology.MATERIALS: This trial was carried out in the Jiangsu Provincial Key Laboratory of Anesthesiology, Xuzhou Medical College from January to March 2000. Totally 30 Sprague-Dawley rats were chosen and balanced randomized into 6 groups: formalin group (n=6), formalin + ketamine group (n=6), ketamine +formalin group (n=6), ketamine group (n=6), formalin+normal saline group (n=3) and normal saline group (n=3). The gender ratio was the same in each group.METHODS: Formalin group:The rats were stimulated for one hour by subcutaneous injection of 0.05 volume fraction of 200 μL in the center of palm of unilateral fore-claw. Formalin +ketamine group: The rats were stimulated for 10 minutes by formalin, then for one hour by intraperitoneal injection of 100 rg/kg ketamine. Ketamine + formalin group: The rats were injected with ketamine for 10 minutes, then with formalin for one hour. Ketamine group: the same dosage of ketamine was intraperitoneally injected into the rats for one hour. Formalin + normal saline group: The rats were stimulated for 10 minutes by formalin, then intraperitoneally given 10 mL/kg normal saline for one hour. Normal saline group: the same volume of normal saline was intraperitoneally injected into the rats for one hour.MAIN OUTCOME MEASURES: ① Behavioral performance of the rats in each group. ② Spinal sections were chosen, and stained with c-fos genetic immunohistochemical and NADPH-d histochemical methods. The changes of the number of Fos-like immuno-positive neurons (FLI) and FLI/nitric oxide synthase (NOS) double-labeled neurons in the 4-layer sections (layer Ⅰ -Ⅱ ,layer Ⅲ-Ⅳ ,layerⅤ-Ⅵ ,layer Ⅶ-X )of spinal dorsal horn of the rats were observed.RESULTS: All the thirty rats entered the stage of result analysis. ① Behavioral changes: The rats of formalin group and formalin+ normal salinegroup had apparent pain response; Several minutes after injection with ketamine, righting reflex disappeared and did not recover at perfusion period.Prolonged sleep was found without obvious pain response performance. ② FLI neuron expression: A lot of FLI positive neurons were found in the spinal dorsal horn of injec tion side of the rats in the formalin group and formalin+ normal saline group, and they distributed principally in the layer Ⅰ - Ⅱ of spinal dorsal horn.The distribution in the ketamine + formalin group and formalin + ketamine group was basically similar to that in the formalin group and formalin + normal saline group, but positive neuron counts were significantly reduced (P ＜ 0.01). ③ The expression of FLI/NOS double-labeled neurons: The number of double-labeled neurons in the spinal dorsal horn layer Ⅰ - Ⅱ of the rats in the ketamine+ formalin group and formalin+ ketamine group were significantly less than that in the formalin group and formalin+normal saline group [(1±1), (1±1), (7±3), (8±3),P ＜ 0.01].CONCLUSION: Some neurons of ipsilateral corresponding spinal segments participate in the transmission and mediation of pain signal. Ketamine can suppress the activities of these neurons and exert antinociceptive effect. The antinococeptive function of ketamine may be caused by the activity depression of the NOS-positive neurons in spinal cord.
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Aim To observe the effects of ketamine on Na+,K+-ATPase,Ca2+-ATPase and NOSase activity in different cerebral cortex in convulsive mice.Methods The mice were randomly divided into blank group,normal saline(NS) group and ketamine 25 mg?kg-1 (KetⅠ),50 mg?kg-1(KetⅡ) group. The animals of blank group were killed directly.Convulsion was induced by intraperitoneally(ip) strychnine(1.5 mg?kg-1) in other groups,and correspond drugs were administered ip before five minutes.Action variety of mice was observed. Animals were killed on 30 minutes after strychnine injection.The activity of Na+,K+-ATPase,Ca2+-ATPase,TNOSase and iNOSase were assessed by spestrophotometric analysis in different cere-bral cortex(forehead,parietal and occipital area).Results Ketamine group could decrease mortality completely. The duration of tonic state in KetⅡ group was significantly shorter than that in KetⅠgroup.Compared with blank group,Na+,K+-ATPase and Ca2+-ATP ase activities were decreased in the group of NS and KetⅠ,and recovered normal level in the group of KetⅡ at parietal and occipital area. TNOS ase activity was decreased by 1/3 in KetⅡ group(P
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AIM:?To?investigate?if?alfentanil?protects?the?isolated?rat?heart?against?myocardial?reperfusion?injury?and?if?the?mechanism?of?this?protection?is?mediated?via?opioid?receptors?and?NO-dependent?pathways. METHODS: Langendorff rat hearts were perfused at constant pressure with Kreb-Henseleit(K-H) buffer for 20 min?and?then?were?perfused?with?test?solution:?K-H?buffer?or?K-H?buffer?containing?alfentanil? 50 ?g?L -1,?alfentanil? 100 ?g?L -1, naloxone 200 ?g?L -1, alfentanil 100 ?g?L -1+naloxone 200 ?g?L -1, L-NAME 100 ?mol?L -1 and alfentanil 100 ?g?L -1+L-NAME 100 ?mol?L -1. After 10 min of this, the hearts were subjected to 25 min normothermic( 37 ℃) global ischemia followed by 30 min reperfusion with the same test solution as before. To evaluate myocardial function, LVEDP, LVDP, ?dp/dt max, HR and CF were measured at the 20th, 25 and 30th minute of perfusion and the 1st, 3rd, 5th, 10th, 20th and 30th minute of reperfusion. After experiment, the NOS and ATP content of myocardium were assessed. RESULTS: Before ischemia, alfentanil 100 ?g?L -1 decreased the HR at the 30th minute compared with the 20th minute(P
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AIM:To study the protective effects of penehyclidine hydrochloride(PHC) on transient forebrain ischemia reperfusion injury in gerbils.METHODS:The model of transient forebrain ischemia reperfusion was established in gerbils by bilateral carotid artery clamping.The effects of PHC on neurological function scores and the morphous of hippocampal pyramidal neuron of gerbils were observed after receiving transient forebrain ischemia reperfusion.SOD activities and contents of MDA in the hippocampus and cortex of gerbils were measured.RESULTS:In the groups of PHC(0.08),(0.24)(mg?kg~(-1)) and atropine,the stroke index was decreased,compared with the ischemia-reperfusion group after the gerbils received transient forebrain ischemia reperfusion for six hours.PHC could reduce the degree of injury in hippocampal pyramidal neuron after ischemia reperfusion for three days.CONCLUSION: PHC has protective effects on transient forebrain ischemia reperfusion injury in gerbils.
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Objective To investigate the effects of GABAA receptor agonist-muscimol and GABAA receptor antagonist-bicuculline on brain cyclic adenosine monophosphate (cAMP) content in rats undergoing isoflurane anesthesia. Methods Forty-eight SD rats of both-sexes weighing 200-250g were randomly divided into 6 groups: group I received intraperitoneal (ip) normal saline (NS) 10ml.kg-1 (control group); group II in which animals inhaled 1.4% isoflurane for 30 min, 30 min after NS ip (isoflurane group);group IE in which animals inhaled 1.4% isoflurane for 30 min, 30 min after muscimol Img-kg ip (muscimol + isoflurane group); group IV in which animals inhaled 1.4% isoflurane for 30min, 30 min right after bicuculline 8 mg.kg-1 ip (bicuculline + isoflurane group); group V received muscimol lmg. kg-1 (muscimol group); group VI received bicuculline 8mg.kg (bicuculline group). The animals were decapitated 1h after 30min isoflurane inhalation or intraperitoneal NS or muscimol or 5min after bicuculline ip (rats developed convulsion within 7 min after bicuculline ip) . Brain was removed immediately for determination of cAMP content of cortex or brain stem. Loss of righting reflex was taken as sign of anesthesia. Brain cAMP content was measured by competitive protein binding assay. Results Muscimol shortened the time of loss of righting reflex induced by isoflurane (P
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Objective To determine the effects of isoflurane on the amino acid neurotransmitter contents in rat cerebral cortex, hippocampus and spinal cord. Methods Sixteen male SD rats weighting 220-280g were randomly divided into two groups: isoflurane group (A) and control group (B). Animals in group A were killed after 30min inhalation of 1.3% isoflurane and cerebral cortex, hippocampus and spinal cord were removed immediately for determination of glutamic acid (Glu), aspartic acid (ASP), glutamine (Gln), GABA and glycine (Gly) levels by high-performance liquid chromatography (HPLC), whereas in group B O2 was inhaled instead of isoflurane. Results As compared with control group, Asp and Glu levels in cerebral cortex and hippocampus decreased markedly while Gly level increased significantly in hippocampus and spinal cord in isoflurane group. Conclusions The inhibition of excitatory amino acid synapse transmission and augmentation of inhibitory amino acid synapse transmission may be involved in the mechanism of isoflurane anesthesia.
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Objective To investigate the effects of isoflurane on cyclic adenosine monophosphate (cAMP ) content of brain in the rats. Methods Fourty SD rats were allocated randomly to 5 groups: no administration(control group,n=8), inhalation of 1.4% isoflurane until losing of righting reflex(loss of righting reflex group,n=8), inhalation of 1.4% isoflurane lasting 30 min(anesthesia group,n=8) ,righting reflex recovery after cessation of 30-min inhalation of 1.4% isoflurane (recoveryⅠ group,n=8) and 30 min after cessation of 30-min inhalation of 1.4% isoflurane (recovery Ⅱ group,n=8). The rats of each group were decapitated at the end of procedures to measure the cAMP content of brain tissue with competitive protein binding assay.Results As compared with that in control group,the cerebrocortical cAMP content only in anesthesia group significantly increased by 49% (P
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AIM To investigate the protective effect of sodium gamma-hydroxybutyrate (?-OH) against cerebral ischemia-reperfusion injury in gerbils and the neuroprotective mechanism of ?-OH. METHODS The occlusion of bilateral carotid arteries of gerbil was used to make the cerebral ischemia-reperfusion models. Different doses of ?-OH were administered intraperitoneally 40 min prior to the onset of ischemia. After 10 min ischemia and 1 h reperfusion, bilateral hippocampus, cortex and striatum were taken out to measure ATPase, SOD and MDA. RESULTS The contents of MDA markedly elevated while Na +,K +-ATPase, Ca 2+ -ATPase and SOD activities decreased in hippocampus, cortex and striatum 1 h after ischemia-reperfusion. ?-OH administered prior to ischemia can partly reverse the elevation of MDA contents and the reduction of SOD activities. ?-OH given after ischemia can still provide partly protective effect. CONCLUSION ?-OH provides significant protective effect against cerebral ischemia-reperfusion injury by protecting ATPase and SOD activities, deleting free radicals and reducing the lipid peroxidation.
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Constant infusion, exponentially declining infusion and program infusion of theophlline were administered to rabbits byadopting the rabbit population pharmacokinetic parameters in this laboratory, and the plasma concentrations of the drug was measured by ul- traviolet spectrophotometry. The results showed that the plasma drug concentrations following exponentially declining infusion and program infusion attained the desired steady-state level at only 30 min, though the T1/2?= 6. 08h, The median absolute value of performance error in pro-gram infusion and exponentially declining infusion was 7. 8% and 14% respectively.
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AIM To investigate the effects of thiopental sodium on nitric oxide synthases (NOS) activity and nitride oxide (NO) in different rats cerebral synaptic membrane. METHODS Forty SD rats were divided randomly into five groups. The animals were injected introperitoneally (ip)thiopental sodium 30 mg?kg -1 or normal saline 10 ml?kg -1 (control group ) respectively. These rats were immediately decapitated before (induction group) and after (anaesthetic group) having disappeared righting reflex, and when righting reflex appeared again (recovery group), and completely conscious (awake group). In order to prepare synapsis, brain tissues were dissected on ice, then homogenized and centrifuged. NOS activity and NO was estimated by spectrophotometry. RESULTS Thiopental sodium 30 mg?kg -1 ip significantly inhibited NOS activity of cortex, brain stem and synaptic membrane as compared with that of normal saline group( P
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Aim To investigate the effect of spinal substance P on the antinociceptive propoties of ketamine. Methods Using behaviors and Fos expression technique,the effects of intrathecal administration (it) of substance P of different dose on the ketamine induced antinociception were observed in the formalin test of mice. Results Compared with NS group, the amount of time that mice spent licking the injected paw was dose-dependently decreased in 20 and 30 mg?kg -1 groups(P
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0.05),but the HPPT was dose-dependently increased in 25 and 50 mg?kg -1 groups(P0.05); on the contrary ,strychnine 0.5,0.75,1.0 ?g(it) decreased the HPPT of propofol-treated mice as doses increased(P0.05). CONCLUSION Propofol can induce antinociception in hot-plate test and acetic acid-induced writhing test of mice. Spinal glycine receptors may play a role in propofol's antinociceptive properties in hot-plate test of mice.