L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine

Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature. IMPLICATIONS: The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.     

七氟醚控制性降压对脑代谢的影响

目的 观察七氟醚控制性降压的效果及对脑氧供需平衡、脑能量代谢的影响,并与硝普钠（ＳＮＰ）降压进行对比。方法 择期手术病人４０例随机分为三组：Ｉ组七氟醚降压组,Ⅱ组七氟醚常压组和Ⅲ组ＳＮＰ降压组。Ｉ组增加七氟醚吸入浓度,Ⅲ组静滴ＳＮＰ溶液,降至基础值的５０％～６０％持续４０ｍｉｎ,连续监测ＭＡＰ、ＨＲ、及ＥＣＧ,并同步采集桡动脉和颈内静脉血行血气分析,计算动－颈内静脉氧含量差（Ｄａ－ｊｖＯ２）;测定     

人尿组织激肽释放酶对兔症状性脑血管痉挛早期扩张脑血管效应的评价

目的 评价人尿组织激肽释放酶对兔症状性脑血管痉挛扩张脑血管效应及神经功能的影响.方法 采用Endo法建立家兔脑血管痉挛模型.40只日本大耳兔中8只由于死亡及出现严重神经功能缺损症状排除于本组.其余32只随机分为4组,每组8只.即生理盐水对照组(枕大池注入生理盐水,A组)、蛛网膜下腔出血组(B组)、人尿组织激肽释放酶治疗组(C组)及尼莫地平治疗组(D组).对每组动物分别行行为学评分、神经功能评分和脑血管造影.结果 B组家兔食量明显降低,神经症状明显;而C、D组食量减少、神经症状均较B组程度轻;A组基本正常.B组兔基底动脉在蛛网膜下腔出血(SAH)后第4、7天痉挛明显,直径分别为(1.5±0.3)mm、(1.4±0.3)mm,与出血前(1.9±0.3)mm比较,差异均有统计学意义(P均<0.05);B组基底动脉痉挛与C组第4、7天比较,差异具有统计学意义(P<0.001);而D组在4、7、14 d动脉痉挛较B组改善不明显.结论 人尿组织激肽释放酶和尼莫地平均能较明显地改善兔症状性脑血管痉挛的神经症状,仉前者早期缓解血管痉挛的效果较尼莫地平更好.     

Role of potassium channels in isoflurane- and sevoflurane-induced attenuation of hypoxic pulmonary vasoconstriction in isolated perfused rabbit lungs

BACKGROUND: Although potassium channels are thought to be responsible for the initiation of hypoxic pulmonary vasoconstriction (HPV), their role in the HPV-inhibitory effect of volatile anesthetics is unclear. The current study tested if the HPV-inhibitory effect of isoflurane and sevoflurane can be affected by changing the potassium-channel opening status with specific potassium-channel inhibitors in isolated rabbit lungs. METHODS: Isolated rabbit lungs were divided into eight groups (n = 6 each in isoflurane groups and n = 8 in sevoflurane groups): those receiving no inhibitor treatment = control-isoflurane and control-sevoflurane groups; those treated with an adenosine triphosphate-sensitive potassium (K(ATP))-channel inhibitor, glibenclamide = glibenclamide-isoflurane and glibenclamide-sevoflurane groups; those treated with a high-conductance calcium-activated potassium (K(Ca))-channel inhibitor, iberiotoxin = iberiotoxin-isoflurane and iberiotoxin-sevoflurane groups; and those treated with a voltage-sensitive potassium (Kv)-channel inhibitor, 4-aminopyridine = 4-aminopyridine-isoflurane and 4-aminopyridine-sevoflurane groups. The effect of anesthetic on HPV was tested by exposure of the lungs to isoflurane at a concentration of 0, 0.5, 1, or 2 minimum alveolar concentration, or to sevoflurane at a concentration of 0, 0.5, 1, or 1.62 minimum alveolar concentration. The relation between anesthetic concentrations and the HPV response was analyzed by the Wagner equation. RESULTS: The inhibition of Kv channels by 4-aminopyridine and K(Ca) channels by iberiotoxin augmented the HPV response. The isoflurane-induced attenuation of HPV was attenuated by voltage-sensitive potassium-channel inhibition with 4-aminopyridine, potentiated by K(Ca)-channel inhibition with iberiotoxin, but not affected by K(ATP)-channel inhibition with glibenclamide. The sevoflurane-induced attenuation of HPV was not affected by any of the potassium-channel inhibitors. CONCLUSIONS: Isoflurane may modulate the HPV response partially through K(Ca) and Kv channels, but sevoflurane may attenuate the HPV response through other pathways rather than through the currently investigated potassium channels in isolated rabbit lungs.     

氯胺酮对家兔内毒素性急性肺损伤的影响

目的研究氯胺酮对家兔内毒素(ET)性急性肺损伤(ALI)的影响。方法采用两次注射脂多糖(LPS)的方法复制家兔ALI模型。动物随机分为四组,每组6只:氯胺酮1组(K1组)、氯胺酮2组(K2组)、LPS组(阳性对照)、生理盐水(NS)组(阴性对照),第2次LPS注射后8 h结束实验,测定以下指标变化:支气管肺泡灌洗液(BALF)中白细胞和肺泡上皮细胞计数、肺水含量、肺通透指数(LPI)、肺组织髓过氧化物酶(MPO)含量、肺组织病理。结果LPS组BALF中白细胞和肺泡上皮细胞数量、肺水含量、LPI和肺MPO含量均较NS组明显上升(P<0.01)。NS组肺病理检查正常;LPS组双肺明显肿胀,表面有点片状出血,轻挤切面有水肿液溢出,镜下有明显肺不张和肺泡萎陷,肺间质增厚,内有大量白细胞浸润,肺血管淤血;K1组与K2组前述各指标和病理变化的程度轻于LPS组,其中K2组又明显好于K1组。结论氯胺酮可减轻LPS注射后家兔ALI程度。     

Intrathecal dexmedetomidine attenuates hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits

BACKGROUND: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia. METHODS: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7). RESULTS: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles. CONCLUSIONS: The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.     

Intrathecal neostigmine prevents intrathecal clonidine from attenuating hypercapnic cerebral vasodilation in rabbits

We previously demonstrated that lumbar intrathecal alpha(2) agonists attenuate hypercapnia-induced cerebral vasodilation. The combination of intrathecal clonidine and neostigmine is being investigated as pain therapy. The effects of their combination on cerebrovascular reactivity are unknown. We allocated rabbits anesthetized with pentobarbital to two groups: (a) clonidine (normal saline followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6), and (b) neostigmine-pretreatment (neostigmine 2 microg/kg followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6). We then evaluated the hypercapnia-induced changes in pial arteriolar diameter in these two groups using the closed cranial window preparation. The pial arteriolar dilator response to hypercapnia was significantly attenuated in the clonidine group (14% +/- 4%, 4% +/- 4%, 6% +/- 6%, and 5% +/- 7% for before and 30, 60, and 90 min, respectively). Neither normal saline nor neostigmine alone induced any change in the cerebral reactivity to hypercapnia. Pretreatment with neostigmine completely prevented the clonidine-induced attenuation of the hypercapnic cerebral vasodilation attenuated by intrathecal clonidine (16% +/- 7%, 15% +/- 6%, 12% +/- 6%, and 16% +/- 8%, respectively).     

氯胺酮对兔蓝斑去甲肾上腺素释放的影响

目的 观察氯胺酮对家兔脑内蓝斑区去甲肾上腺索(NE)释放的影响，以探讨其心血管反应是否有中枢机制参与。方法选择雄性新西兰兔9只，静脉注射氯胺酮2mg/kg，并以50μg/(kg·min)的速率静脉泵注20min。使用推挽灌流法收集蓝斑区引流脑脊液(CSF)，用高效液相色谱法测定NE 浓度。结果 静脉注射氯胺酮后及泵注维持期间，CSF 中 NE 浓度升高(P<0.01)，从(16±3)pg/ul上升至(32±4)pg/μl；停药0～20min 期间，CSF 中 NE 浓度有所下降(P<0.05)，但仍高于基础值(P<0.01)；停药后21～40min 期间，CSF 中 NE 浓度恢复至基础值水平。结论 氯胺酮可升高蓝斑区 NE的释放，提示氯胺酮的心血管反应可能有中枢机制参与。     

Effects of subanesthetic ketamine on regional cerebral glucose metabolism in humans

BACKGROUND: The authors have recently shown with positron emission tomography that subanesthetic doses of racemic ketamine increase cerebral blood flow but do not affect oxygen consumption significantly. In this study, the authors wanted to assess the effects of racemic ketamine on regional glucose metabolic rate (rGMR) in similar conditions to establish whether ketamine truly induces disturbed coupling between cerebral blood flow and metabolism. METHODS: 18F-labeled fluorodeoxyglucose was used as a positron emission tomography tracer to quantify rGMR on 12 brain regions of interest of nine healthy male volunteers at baseline and during a 300-ng/ml ketamine target concentration level. In addition, voxel-based analysis was performed for the relative changes in rGMR using statistical parametric mapping. RESULTS: The mean +/- SD measured ketamine serum concentration was 326.4+/-86.3 ng/ml. The mean arterial pressure was slightly increased (maximally by 16.4%) during ketamine infusion (P < 0.001). Ketamine increased absolute rGMR significantly in most regions of interest studied. The greatest increases were detected in the thalamus (14.6+/-15.9%; P = 0.029) and in the frontal (13.6+/-13.1%; P = 0.011) and parietal cortices (13.1+/-11.2%; P = 0.007). Absolute rGMR was not decreased anywhere in the brain. The voxel-based analysis revealed relative rGMR increases in the frontal, temporal, and parietal cortices. CONCLUSIONS: Global increases in rGMR seem to parallel ketamine-induced increases in cerebral blood flow detected in the authors' earlier study. Therefore, ketamine-induced disturbance of coupling between cerebral blood flow and metabolism is highly unlikely. The previously observed decrease in oxygen extraction fraction may be due to nonoxidative glucose metabolism during ketamine-induced increase in glutamate release.     

亚低温下氯胺酮对大鼠窒息性脑缺血后脑组织谷氨酸和丙二醛含量的影响

目的 探讨亚低温时氯胺酮对大鼠窜息性脑缺血后脑组织谷氨酸(Glu)和丙二醛(MDA)含量的影响.方法 50只Wistar大鼠随机均分为五组:窒息模型组(A组)、氯胺酮组(B组)、亚低温组(C组)、氯胺酮+亚低温组(D组)、假手术对照组(E组).测定大鼠大脑组织在发生窒息性脑缺血/缺氧后Glu和MDA含量的变化.结果 与E组比较,A组脑组织Glu含量明显升高(P<0.01);与A组比较,B、C、D组Glu含量明显降低且呈明显递减(P<0.01).与E组比较,A、B、C、D组MDA含量明显增高(P(0.01);与A组比较,B、C、D组MDA含量明显降低且基本呈递减趋势(P<0.01).结论 氯胺酮在亚低温下可抑制脑组织缺血损伤后内源性Glu的释放,减少脂质过氧化终产物MDA的生成.     

5-羟色胺受体对小鼠异氟烷、七氟烷遗忘作用的影响

目的 探讨5-羟色胺(5-hydroxytry ptamine,5-RT)受体与吸入麻醉药异氟烷、七氟烷遗忘作用的关系.方法 建立小鼠腹腔注射异氟烷、七氟烷遗忘模型,在跳台、避暗实验中观察和记录不同剂量5-HT受体拮抗剂(WAY100635)侧脑室注射对跳台潜伏期、步入潜伏期、错误次数的影响.结果 侧脑室注射5-HT受体拮抗剂可延长异氟烷、七氟烷所致记忆障碍小鼠的跳台潜伏期(P＜0.05)、步入潜伏期(P＜0.05),减少错误次数(P＜0.05).结论 5-HT受体介导了异氟烷、七氟烷的遗忘作用.     

Effects of thiopental, pentobarbital, and ketamine on endothelin-induced constriction of porcine cerebral arteries

Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin-induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine.     

丰富环境对七氟醚吸入诱发新生大鼠远期认知功能障碍的影响

目的观察丰富环境对七氟醚吸入诱发新生大鼠远期认知功能障碍的影响。方法 6日龄新生雄性SD大鼠30只随机均分为三组:O2+标准环境组(OS组)、七氟醚麻醉+标准环境组(SS组)和七氟醚麻醉+丰富环境组(SE组)。SS、SE组分别在日龄6、7、8d时,每天接受1次2h的3%七氟醚麻醉,氧浓度100%;O2组在相应日龄吸入100%氧气。出生后第8天起至行为学测试前分别进行标准环境和丰富环境饲养,连续4周。第35天行旷场实验。第36天行场景性、条件性恐惧实验训练。第37、38天行场景性、条件性恐惧实验测试。行为学测试结束后2h,每组各取4只大鼠海马组织,采用Western blot法检测Synapsin-1、PSD-95、c-fos及BDNF含量。结果旷场实验测试中,三组探索路程和中央格停留时间差异无统计学意义。场景性恐惧实验测试中,与SS组比较,OS、SE组僵直反应明显增加(P0.05)。条件性恐惧实验测试中,三组僵直反应差异无统计学意义。与SS组比较,OS、SE组海马Synapsin-1、PSD-95、c-fos和BDNF含量明显增加(P0.05)。结论七氟醚麻醉可致新生大鼠远期海马依赖性认知功能受损,丰富环境可改善此种损伤,其机制可能与增加突触可塑性相关蛋白表达有关。     

Effects of anesthesia and recovery from ketamine racemate and enantiomers on regional cerebral glucose metabolism in rats

BACKGROUND: Unlike most anesthetics, ketamine racemate (S, R (+/-)-ketamine) induces heterogenous changes in cerebral metabolism. S, R (+/-)-ketamine is an equimolar mixture of two enantiomers, S (+)-ketamine and R (-)-ketamine, which differ in affinity for neuroreceptors and pharmacologic activities. This study investigated comparatively the effects of ketamine racemate and enantiomers on cerebral metabolism. METHODS: Regional cerebral metabolic rates for glucose (rCMRglc) were determined with the quantitative, autoradiographic [C]2-deoxy-d-glucose technique in 40 brain regions of Fischer-344 rats. rCMRglc were measured in three groups of rats during equimolar anesthesia, 10 min after intraperitoneal injection of 170 mg/kg S, R (+/-)-ketamine, S (+)-ketamine, or R (-)-ketamine; in three groups of rats during recovery from equivalent anesthesia, 20 min after intravenous injection of 20, 12.5, and 30 mg/kg S, R (+/-)-ketamine, S (+)-ketamine, or R (-)-ketamine; and in two groups of saline-injected control rats. RESULTS: S, R (+/-)-ketamine and S (+)-ketamine induced a sustained anesthesia; deep rCMRglc decreases in 22 and 14 cortical, thalamic, cerebellar, and brainstem regions; and rCMRglc increases in two limbic regions (average decreases, 23 and 15%). R (-)-ketamine determined a shorter anesthesia, lesser rCMRglc decreases in 11 brain areas, and marked rCMRglc increases in 14 basal ganglia and limbic regions (average decrease, 4%). S, R (+/-)-ketamine, S (+)-ketamine, and R (-)-ketamine all produced postanesthetic behavioral activation; widespread rCMRglc increases in 28, 16, and 20 cortical, thalamic, basal ganglia, limbic, and brainstem regions; and rCMRglc decreases in few auditory and limbic regions (average increases, 35, 13, and 20%). CONCLUSIONS: S, R (+/-)-ketamine and S (+)-ketamine anesthesia but not R (-)-ketamine anesthesia induced widespread rCMRglc reductions that were unreported but are typical of gaseous and intravenous general anesthetics. Postanesthetic recovery led to divergent, sharp behavioral and rCMRglc activations. The relation to dose of behavioral and rCMRglc effects differs from those of aminergic agents and resembles those of N-methyl-d-aspartate receptor antagonists, suggesting that ketamine racemate and enantiomers may preferentially interact with this receptor type.     

Effects of raloxifene on cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits

Background

The aim of this study was to investigate the ability of a SERM, RLX, to prevent vasospasm in a rabbit model of SAH.

Methods

Thirty-four New Zealand white rabbits were allocated into 3 groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH [n = 12]), (2) SAH only (n = 12), and (3) SAH plus RLX (n = 10). Basilar artery lumen areas and arterial wall thickness were measured to assess vasospams in all groups.

Results

There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (P < .05). The difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements in the RLX-treated group was statistically significant (P < .05). The difference between the SAH group and the SAH + RLX group was also statistically significant (P < .05).

Conclusions

These findings demonstrate that RLX has marked vasodilatatory effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this SERM drug could be used as possible anti-vasospastic agent in patients without major adverse effects.     

Effects of phosphodiesterase-III inhibitors on sevoflurane-induced impairment of rat diaphragmatic function

BACKGROUND: Volatile anesthetics are known to cause diaphragmatic dysfunction using a whole body model. The first aim of the current study was to compare the impairing effect of halothane and sevoflurane on diaphragmatic contractile functions under unfatigued and fatigued conditions. The second purpose was to determine whether phosphodiesterase-III inhibitors can attenuate sevoflurane-potentiated reduction of contractility after fatigue. METHODS: Using rat-isolated muscle strips, diaphragmatic twitch characteristics and tetanic contractions were measured before and after muscle fatigue, which was induced by repetitive tetanic contraction with or without exposure to halothane (1-3 MAC) or sevoflurane (1-3 MAC). Diaphragmatic functions were further assessed with exposure to 3 MAC sevoflurane in the presence and absence of milrinone, or olprinone. Cyclic adenosine monophosphate (cAMP) concentrations in the fatigued diaphragm were also measured. RESULTS: Halothane (1-3 MAC) or sevoflurane (1-2 MAC) did not induce a direct inotropic effect under unfatigued and fatigued conditions. Sevoflurane at 3 MAC enhanced fatigue-induced impairment of twitch and tetanic tensions. Clinically relevant concentrations of olprinone improved the sevoflurane-induced potentiation of diaphragmatic dysfunction following fatigue, accompanied by restoration of diaphragmatic cAMP levels, although milrinone failed to do so. CONCLUSION: Our findings suggest that sevoflurane has a greater decreasing effect on diaphragmatic contractility after fatigue than halothane, and that the clinical dose of olprinone surmounts the disadvantage of sevoflurane in various conditions where diaphragmatic fatigue is predisposed.     

利多卡因复合氯胺酮对全脑缺血大鼠海马细胞凋亡的影响

Objective To investigate the effect of lidocaine combined ketamine to the cells necrosis and apoptosis in the CA1 region of rat hippoeampus following global cerebral ischemia-reperfusion. Methods Sixty adult Wistar rats were randomly divided into 6 groups:control group(Ⅰ, n=4),sham operation group (Ⅱ, n=4), model group (Ⅲ, n =4), lidoeaine group (Ⅳ, n =16), ke-tamine group(Ⅴ, n=16), lidocaine and ketamine group (Ⅵ, n=16). The global cerebral ischemia (10 min) was induced by the use of the four-vessel occlusion method. Group Ⅳ,Ⅴ,Ⅵ intraperitoneally injected the lidocaine 10mg/kg, ketamine 10 mg/kg or lidocaine combined ketamine 10 mg/kg. The effect of cells necrosis and apoptosis was detected by using HE staining and TUNEL methods. Results Compared with group Ⅱ the numbers of ischemia neuron of group Ⅳ, Ⅴ, Ⅵ had significant deviation (P<0.05) in 24 h, and group Wl had significant decreased than group Ⅳ, Ⅴ(P<0.05). The isehemia neurons peak presented in 24 h. Compared with group Ⅱ the numbers of apoptosis of group Ⅳ,Ⅴ,Ⅵ had significantly deviation (P<0.05)in 24 h, and group Ⅵ had significantly decreased than group Ⅳ,Ⅴ (P<0.05). The apoptosis peak presented in 24 h and 48 h, and decreased during reperfusion time. Conclusion Li-doeaine combined ketamine can reduce the cell necrosis and apoptosis after global erebral isehemia-reperfusion in rats hippocampus.