Effects of vasopressors on contractile and phosphatidylinositol responses of rat trachea

Purpose. Vasopressors, such as dopamine (DA), norepinephrine (NE), and phenylephrine (Phe), are commonly used during anesthesia to increase blood pressure through α₁-adrenoceptors. The present study was designed to examine the effects of DA, NE, and Phe on the contractile and phosphatidylinositol (PI) responses of the rat trachea induced by a muscarinic agonist, carbachol (CCh). Methods. A rat tracheal ring was suspended between two stainless-steel hooks in Krebs-Henseleit (K-H) solution. Contraction was induced with 0.55 μM CCh, and 30 min later DA, NE, or Phe was added. The tracheal slices were incubated in K-H solution containing LiCl, ³[H]myo-inositol, and CCh in the presence or absence of DA, NE, or Phe. The ³[H]inositol monophosphate (IP₁) formed was measured. Results. CCh caused tracheal ring contraction. NE attenuated CCh-induced contraction at a dose of 1 μM or greater and had a maximal effect at 3 μM. DA and Phe did not affect CCh-induced contraction. CCh-induced IP₁ accumulation was potentiated significantly by NE and Phe, but not by DA. Conclusion. Although NE and Phe potentiated CCh-induced IP₁ accumulation, they could not potentiate CCh-induced contraction, suggesting that in clinical settings, vasopressors such as NE, DA, and Phe might be safely used in patients with asthma. Received: February 25, 2002 / Accepted: July 2, 2002 Acknowledgments. This study was supported in part by a Grant-in-Aid for Scientific Research C (no. 10671421), from the Ministry of Education, Science, and Culture, Japan. Address correspondence to: O. Shibata     

Effects of ATP-sensitive potassium channel openers on the contractile and phosphatidylinositol responses of the rat trachea

Purpose. Although ATP-sensitive potassium channel openers suppress airway smooth muscle contraction, their potencies are different and the mechanisms involved are not fully understood. We examined the effects of cromakalim and Y-26763, a novel ATP-sensitive potassium channel opener, on the contractile and phosphatidylinositol responses of the rat trachea. Methods. Thirty-six male Wistar rats, weighing 250–350 g, were used. In the experiment on contractile response, active contraction was induced with 0.55 μM carbachol in the presence or absence of cromakalim or Y-26763. In the experiment on phosphatidylinositol response, the tracheal slices were incubated with [³H]myo-inositol, 0.55 μM carbachol, and cromakalim or Y-26763, and the formation of [³H]inositol monophosphate (IP₁), a degradation product of phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance (P < 0.05) was determined by analysis of variance (ANOVA). Results. Carbachol-induced tension was attenuated by both cromakalim and Y-26763, the latter displaying significantly greater potency. Carbachol-induced IP₁ accumulation was influenced neither by cromakalim nor by Y-26763. Conclusion. Both cromakalim and Y-26763 have effects on airway smooth muscle relaxation. Carbachol-induced IP₁ accumulation was influenced neither by cromakalim nor by Y-26763, suggesting that phosphatidylinositol response may not be a common pathway for the effect of ATP-sensitive potassium channel openers. Received: January 15, 2002 / Accepted: June 14, 2002 Acknowledgment. This study was supported in part by Grant-in-Aid for Scientific Research C, no. 10671421, from the Ministry of Education, Science, and Culture, Japan. Address correspondence to: O. Shibata     

Succinylcholine potentiates acetylcholine-induced contractile and phosphatidylinositol responses of rat trachea

Purpose Although succinylcholine (SCh) is often used as a muscle relaxant in electroconvulsive therapy, its influence on airway reactivity has not been fully investigated. We examined the effects of SCh on acetylcholine (ACh)-, carbachol (CCh)-, and electrical field stimulation (EFS)-induced contractions, and on the ACh-induced phosphatidylinositol (PI) response of rat trachea. Methods Thirty-two male Wistar rats weighing 250–350 g were used. The trachea was rapidly isolated and cut into 3-mm-wide rings. The resting tension was adjusted periodically to 1.0 g during the equilibration period. ACh, 1 μM; carbachol (CCh), 0.05 μM; or neither of them, was added, and SCh was then added at 1–300 μM final concentrations, and ring tension was examined. Contractions were elicited by EFS in the presence or absence of 100 μM SCh. Tracheal slices were incubated with [³H] myo-inositol, 1 μM ACh, and various concentrations of SCh. The accumulation of [³H] inositol monophosphate (IP₁) was measured. Results SCh did not affect the tension by itself without ACh, or with CCh, but SCh potentiated the ACh-induced contraction of rat trachea at concentrations of 10 μM or more (50% effective concentration [EC₅₀]; 43.6 μM). SCh produced a significant increase in the amplitude and duration of EFS-induced contractions. SCh, at concentrations of 10 μM and 100 μM, potentiated ACh-induced IP₁ accumulation. Conclusion SCh potentiated ACh-induced, but not CCh-induced, contractile and PI responses, and enhanced EFS-induced contraction of rat trachea, suggesting that competition for butyrylcholinesterase (BChE) in airway smooth muscle could be involved in the potentiation by SCh of ACh-induced airway smooth muscle contraction.     

Effects of propofol and ketamine on ATP-induced contraction of the rat trachea

Purpose ATP causes airway smooth-muscle contraction in patients with asthma and chronic obstructive pulmonary disease. Propofol and ketamine attenuate the airway smooth-muscle contraction induced by histamine and acetylcholine. However, it is not clear whether propofol and ketamine affect the ATP-induced airway smooth-muscle contraction. Methods We examined the effects of propofol and ketamine on the ATP-induced contraction and ATP-P²-purinoceptor binding. Results Propofol attenuated the ATP-induced contraction in a dose-dependent manner, with a 50% inhibitory concentration of 54 ± 22 μM. Ketamine at 300 μM attenuated the ATP-induced contraction. In the binding study, propofol attenuated the binding of the P²-purinoceptor with [³H]-ATP in a dose-dependent manner, while ketamine did not attenuate this binding. Conclusion Propofol attenuates ATP-induced contraction through the inhibition of ATP-P²-purinoceptor binding.     

A dose-response study of anticholinesterase drugs on contractile and phosphatidylinositol responses of rat trachea

We investigated whether anticholinesterase drugs in large doses inhibit muscarinic receptors of airway smooth muscle. In vitro measurements of isometric tension and [(3)H]inositol monophosphate (IP(1)) that formed were conducted by using rat tracheal rings or slices. Neostigmine and pyridostigmine caused muscular contraction and IP(1) accumulation in small doses (10 microM and < or = 100 microM, respectively), but they attenuated muscular contraction and IP(1) accumulation in larger doses (1000 microM). Edrophonium did not affect the smooth muscle tone and IP(1) levels. Neostigmine, pyridostigmine, and edrophonium attenuated the carbachol (5.5 microM)-induced smooth muscle contraction and IP(1) accumulation, when administered in large doses (1000 microM). The attenuation of contraction by neostigmine at large doses was not affected by methoctramine, an M(2) muscarinic receptor antagonist, but was reversed by washing with fresh Krebs-Henseleit solution. The results suggest that anticholinesterase drugs have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy. Implications: Neostigmine and pyridostigmine, but not edrophonium, have dual effects on the tension and phosphatidylinositol responses of rat trachea. Large doses of anticholinesterase drugs cause airway smooth muscle relaxation, which may be seen in patients with myasthenia gravis who have received excessive anticholinesterase therapy.     

Comparative effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility in dogs

Purpose. The present study was carried out to determine the direct effects of etomidate, ketamine, propofol, and fentanyl on myocardial contractility, and whether fentanyl would enhance the myocardial depression caused by propofol. Method. The anesthetics were injected directly into the circuit that supplied blood to the left circumflex coronary artery (LCX) in anesthetized open-chest dogs. Myocardial contractility was evaluated from measurements of percent segmental shortening (%SS). Results. Etomidate, ketamine, and propofol significantly reduced %SS in a dose-dependent manner. The %SS values with 1.6 and 3.2 mg of etomidate were similar to those with 3.2 and 6.4 mg of ketamine, respectively, and the %SS value with 6.4 mg of propofol was similar to those with 3.2 and 6.4 mg of ketamine. Fentanyl alone had no effects on myocardial performance and did not influence the effect of propofol on %SS. Conclusion. On the basis of clinical doses, the direct myocardial depressant effect of ketamine is more than twice as potent as that of etomidate and slightly more than that of propofol. Fentanyl has no inotropic effect and does not enhance the direct myocardial depressant effect of propofol. Received for publication on June 22, 1998; accepted on October 14, 1998     

氯胺酮对培养心肌细胞的直接作用及其机制

目的 研究氯胺酮对培养心肌细胞的直接作用及其机制。方法 分离ＳＤ乳鼠心室肌细胞培养４～５天,分别加入终浓度为０、１０、４０和１６０μｇ／ｍｌ的氯胺酮作用２．５小时。测定细胞搏动功能、心肌酶活性（ＬＤＨ和ＣＫ）、细胞存活率、细胸内静息Ｃａ＾２＋以及加入５０ｍｍｏｌ／Ｋ氯化钾激发经细胞膜电压门的Ｃａ＾２＋通道内流的瞬息ＣＡ＾２＋。结果１０μｇ／ｍｌ氨胺酮对心机细胞搏动频率及强度无明显影响,〉４０μｇ／     

氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞对腹股沟疝患儿术中应激反应的影响

目的探讨氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞对腹股沟疝患儿术中应激反应的影响。 方法选取2015年11月至2017年12月,保定市儿童医院82例腹股沟疝患儿的临床资料,通过随机数字表法分为对照组与试验组,每组患儿41例。对照组采用氯胺酮静脉全身麻醉,试验组采用氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞。统计2组麻醉前（T1）、麻醉后10 min（T2）、术后即刻（T3）、术后8 h（T4）应激反应指标[皮质醇、白细胞介素-6（interleukin 6,IL-6）]水平、氯胺酮用量、苏醒时间、术后5、60、120 min时疼痛的改良面部表情评分（facial expression scoring,FLACC）及苏醒期躁动评分（awakening period score,AS）、不良反应发生率。 结果T2时2组血清皮质醇、IL-6水平较T1时期增高,但试验组低于对照组（P<0.05）,T3及T4时2组血清皮质醇、IL-6水平较T2时期降低,但试验组低于对照组（P<0.05）;试验组氯胺酮用量少于对照组、苏醒时间短于对照组（P<0.05）;术后5、60、120 min试验组FLACC及AS分值低于对照组（P<0.05）;试验组呕吐（7.32%）、躁动（12.20%）、嗜睡（9.76%）发生率低于对照组（P<0.05）。 结论腹股沟疝患儿手术治疗过程中采取氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞,可减少氯胺酮用量,缩短苏醒时间,减轻术中应激反应程度,还有利于减轻术后疼痛感及躁动程度,且可降低不良反应发生率。     

Effects of amitriptyline, a tricyclic antidepressant, on smooth muscle reactivity in isolated rat trachea

Purpose  This study was designed to investigate the action of amitriptyline, a tricyclic antidepressant, on airway smooth muscle reactivity and its underlying mechanisms. Methods  In isolated rat trachea, isometric force was recorded to examine the effects of amitriptyline on the contractile response to acetylcholine (ACh), electrical field stimulation (EFS), calyculin A (a myosin light chain phosphatase inhibitor), and sphingosylphosphorylcholine (SPC; a Rhokinase activator). In addition, inositol monophosphate (IP1) accumulation was measured to examine its effects on inositol 1, 4, 5-trisphosphate (IP₃) production during stimulation with ACh. Results  Amitriptyline inhibited the contractile responses to ACh, EFS, calyculin A, and SPC, with the concentrations of amitriptyline (mean ± SD) required to exert 50% inhibition (IC₅₀) being 4.3 ± 1.3 μM, 3.2 ± 1.6 μM, 256.4 ± 106.4 μM, and 98.2 ± 21.8 μM, respectively. In addition, amitriptyline (10 μM) eliminated the ACh (10 μM)-induced IP₁ accumulation. Conclusion  The results suggest that amitriptyline does not influence tracheal smooth muscle reactivity at clinical concentrations (<1 μM), but attenuates the reactivity at supraclinical concentrations (≥1 μM). The attenuated response to ACh brought about by amitriptyline is presumably due, at least in part, to the inhibition of phosphatidylinositol (PI) metabolism. The ability of amitriptyline to inhibit the calyculin Ainduced contraction suggests that amitriptyline also inhibits the Ca²⁺-calmodulin-myosin light chain pathway independently of the inhibition of PI metabolism. Finally, the difference between the IC₅₀ values for SPC-induced contraction and those for calyculin A-induced contraction suggests that amitriptyline may also inhibit the Rho-kinase pathway.     

氯胺酮对大鼠心肌细胞内游离钙的影响

目的　探讨氯胺酮对大鼠心肌细胞内游离钙的影响及其作用机制。方法　原代培养的SD大鼠心室肌细胞 ,用钙敏荧光探针Fluo 3/AM负载染色后 ,根据实验中加入氯胺酮终浓度不同分为六组 ,采用激光扫描共聚焦显微镜 ,测定心肌细胞内钙荧光强度的基础值及加入氯胺酮后 5min以及后续加入 4 0mM氯化钾 (KCl)或 1 0mM咖啡因后细胞内钙荧光强度值。结果　 (1 )≤ 1 0 0 μM的氯胺酮对静息心肌细胞内钙荧光强度无明显影响 ,而 30 0 μM的氯胺酮降低钙荧光强度 (P <0 0 1 ) ;(2 )KCl和咖啡因使细胞内钙荧光强度较基础值均明显升高 (P <0 0 1 ) ;氯胺酮剂量依赖性地抑制KCl诱发胞内钙荧光强度升高的幅度 ,尤以 1 0 0和 30 0 μM氯胺酮组明显 ;而各浓度的氯胺酮不抑制咖啡因诱发胞内钙荧光强度的升高 (P >0 0 5 )。结论　 1、1 0和 6 0 μM的氯胺酮可能不抑制整体状态下的心肌收缩 ;而 1 0 0和 30 0 μM的氯胺酮对心肌有剂量依赖性的负性肌力效应 ,其机制可能是氯胺酮抑制了胞外Ca2 + 经膜电压依赖性钙通道内流 ,胞内游离钙浓度降低所致 ,但不影响肌浆网释钙功能。     

Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs

PURPOSE: Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphatidylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-ChE drugs. METHODS: Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (1) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), an M3 muscarinic receptor antagonist, on neostigmine- or pyridostigmine-induced contraction of rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses. PI response. The tracheal slices were incubated in K-H solution containing LiCl and 3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist. 3[H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. RESULTS: Carbachol (0.1 microM), neostigmine (1 microM), pyridostigmine (10 microM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmine-induced contraction. Neostigmine- or pyridostigmine-induced IP1, accumulation was inhibited by 4-DAMP. CONCLUSIONS: The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.     

氯胺酮对大鼠脑内cAMP含量的影响

目的 动态观察氯胺酮对大鼠不同脑区3′5′－环腺苷酸（cAMP)含量的影响。方法 SD大鼠32只,随机分为对照组、麻醉组、恢复I组和恢复Ⅱ组。对照组腹腔注射（ip)生理盐水10ml/kg,其余各组均为ip氯胺酮100mg/kg,对照组在注射生理盐水后5分钟断头取材,麻醉组、恢复I组和恢复Ⅱ组分别在翻正反射消失后、翻正反射恢复后和动物完全清醒后断头取材。用蛋白竞争法分别测定大脑皮层、海马和脑干的cAMP含量。结果 大鼠ip氯胺酮100mg/kg明显增加大脑皮层cAMP含量,翻正反向恢复后比翻正反向消失时增加的幅度更大（P＜0．05或P＜0．01）,动物完全清醒后cAMP含量恢复（与对照组相比,P＞0．05）;对海马cAMP含量无明显影响;在脑干则表现为恢复Ⅱ组cAMP含量明显升高（P＜0．05）,而麻醉组和恢复I组无变化（P＞0．05）。结论 cAMP信号转导系统在氯胺酮全麻机理中可能发挥重要作用。     

阈下氯胺酮复合强效镇痛药及咪唑安定用于静脉麻醉

３０例拟在全麻下行择期手术的患者随机分为三组。Ｆ组用阈下氯胺酮、咪唑安定和芬太尼维持麻醉，Ｓ组和Ｄ组分别用舒芬太尼和二氢埃托啡代替芬太尼。实验结果显示，三组患者麻醉中血压、心率保持稳定，在机械通气的条件下，心排血量、每搏量有所降低。手术后患者意识能较快恢复，Ｓ组平均于术后６．５分、Ｆ组８．６分、Ｄ组１２．８分达拔管标准。术后随访除一例患者（Ｄ组）认为麻醉尚可外，余皆表示满意。结果表明本组静脉麻醉方法安全、有效、实用。     

氯胺酮对离体大鼠肝细胞的毒性作用

应用离体大鼠肝细胞模型研究氯胺酮的肝毒性。氯胺酮能抑制以丙氨酸为底物的肝细胞糖异生的作用，这种抑制作用具有剂量相关性。氯胺酮对肝细胞应用葡萄糖合成乳酸的作用无抑制作用。这种静脉麻醉药无促进离休鼠肝细胞释放钾离子、谷雨转氨酶、乳酸脱氢酶的作用。结果提示，即使大于临床麻醉剂量１０倍以上的氯胺酮，对肝细胞仍是安全的。     

7种常用静脉麻醉药对血流动力学影响的比较

比较常用静脉麻醉药对血流动力学的影响。方法：８０９例拟行全麻醉患者随机分成八组,分别给予生理盐水１０ｍｌ、硫喷妥钠６ｍｇ／ｋｇ、异丙酚２．５ｍｇ／ｋｇ咪唑安定０．３ｍｇ／ｋｇ,依托咪酯丙二醇制剂０．３ｍｇ／ｋｇ,依托咪酯乳剂０．３ｍｇ／ｋｇ、氯胺酮２ｍｇ／ｋｇ和芬太尼５μｇ／ｋｇ。用Ｕｌｔｉｍａ监测仪和阻抗法记录并计算血液动力学有关参数。结果：ＢＰ而言,其降幅排序为异丙酚〉咪唑安定〉硫喷妥钠〉硫喷     

氟哌啶醇对氯胺酮诱导的热休克蛋白70在大鼠海马中表达的影响

目的 研究氟哌啶醇对于氯胺酮诱导的热休克蛋白70（HSP70）在大鼠海马中表达的影响,探讨氟哌啶醇能否预防或治疗氯胺酮导致的脑损害。方法 选择48只大鼠,随机分为8组,分别在腹腔注射氯胺酮80．0mg/kg前后给予不同剂量氟哌啶醇（1．0,5．0,10．0mg/kg),24h后取鼠脑,应用HSP70单克隆抗体免疫组化染色检测大鼠海马中HSP70的表达,并用MIAS－2000图文分析系统分析大鼠海马HSP70阳性细胞百分率、阳性细胞密度和灰度值。结果 单独应用氯胺酮可在大鼠海马表达HSP70;预先给予氟哌啶醇能抑制氯胺酮诱导的HSP70表达,且随着剂量的增加,其抑制作用增强;在使用氯胺酮后给予氟哌啶醇,不能减少HSP70的表达。结论 氯胺酮可诱导HSP70在海马的表达,提示海马的神经元可能受到损害;氟哌啶醇可以预防氯胺酮所致的神经元损害,但对已造成的神经元损害无治疗作用。     

氯胺酮对体外培养大鼠神经干细胞增殖与凋亡的影响

目的探讨氯胺酮对体外培养夫鼠神经干细胞(NSC)增殖与凋亡的影响。方法采用无血清培养和单细胞克隆技术,在大鼠海马分离培养具有单细胞克隆能力的细胞群,采用免疫荧光细胞化学技术证实为NSC。将NSC以5×10~4/孔接种于96孔培养板中,分别加入浓度为0(未加氯胺酮)、5、10、20、50、100、200、500、1000 mmol·L~(-1)氯胺酮,每个浓度5孔。采用四甲基偶氮唑蓝比色法检测NSC光密度(OD),并计算生长抑制率(RI)。采用流式细胞仪测定氯胺酮浓度为0、10、100、500、1000 mmol·L~(-1)时NSC凋亡率。结果与氯胺酮浓度0时比较,200、500、1000 mmol/L氯胺酮可降低NSC OD,升高RI,10、100、500、1000 mmol·L~(-1)氯胺酮可升高NSC凋亡率(P＜0．05或0．01)。结论氯胺酮对体外培养大鼠NSC增殖有抑制作用,并能诱导NSC凋亡,且该作用与氯胺酮浓度有关     

氯胺酮对外周神经传导的影响

１２只戊巴比妥钠麻醉的猫，观察了神经干局部和静脉使用氯胺酮（ｋｅｔａｍｉｎｅ，ＫＥＴ）对神经干复合动作电位的影响。结果显示：（１）局部施加较高浓度的ＫＥＴ（３．６、７．２、３６、７２和１８０ｍｍｏｌ）对Ａβ，Ａ和Ｃ波具非选择性可逆性抑制作用，且与剂量呈正相关。而较低浓度的ＫＥＴ（０．９和１．８ｍｍｏｌ）对动作电位不仅不抑制，反而有兴奋效应；（２）静脉注射 ＫＥＴＳ和 １０ｍｇ／ｋｇ对约半数的 Ａβ，Ａ和 Ｃ波有兴奋作用，而无抑制效应。上述结果表明，ＫＥＴ可以通过非突触作用直接影响外周神经冲动的传导，而较高浓度和较低浓度的ＫＥＴ则可通过不同的机制分别对神经冲动的传导产生抑制和兴奋作用。     

氯胺酮对大鼠全心缺血/再灌注时心肌c-fos基因表达的影响

目的研究氯胺酮对大鼠全心缺血/再灌注时心肌c-fos基因表达的影响。方法Wistar大鼠40只,随机分为5组(各8只)正常对照组(C组);缺血/再灌注对照组(CR组)和高(KH)、中(KM组)、低(KL组)浓度氯胺酮灌注组(氯胺酮浓度分别为1×10-3、1×10-4和1×10-5mol/L)。提取心肌组织总RNA,经逆转录多聚酶链反应得到cDNA扩增产物,选择γ-actinmRNA作为内参照,用计算机成像分析系统分析曲线下峰面积,计算密度值。结果与C组相比,CR、KH、KM和KL组c-fosmRNA表达水平明显增高(P＜0.01和P＜0.05)。与CR组相比,KH、KM和KL组c-fosmRNA表达水平明显降低(P＜0.05和P＜0.01)。KM和KL组c-fosmRNA表达水平低于KH组(P＜0.05),但KM和KL组相比则无统计学差异(P＞0.05)。结论c-fos基因可能参与心肌缺血/再灌注损伤及保护的基因调节。氯胺酮能显著抑制心肌c-fos基因的表达,且中、低浓度氯胺酮较高浓度有效。     

氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响

目的观察不同剂量氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响。方法36只成年雄性Wistar大鼠随机分为6组,每组6只,A组(对照组):静脉输注生理盐水10ml·kg-1·h-1;B组:静脉注射内毒素(LPS)5mg·kg-1,1min后静脉输注生理盐水10ml·kg-1·h-1;C组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮0.5mg·kg-1·h-1;D组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮5mg·kg-1·h-1;E组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮50mg·kg-1·h-1;F组:静脉输注氯胺酮50mg·kg-1·h-1。记录注射LPS后30、60、90、120min时平均动脉压(MAP)和心率(HR),并于注射LPS后120min时放血处死大鼠,测定外周血单核细胞(PBMC)中NF-κB含量及血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度。结果与基础值比较,B组注射LPS后MAP下降,HR增快,PBMC中NF-κB含量增加,血浆TNF-α、IL-6浓度升高。与B组比较,E、F组.MAP在注射LPS后120min升高,E组HR在注射LPS后90、120min、F组HR在注射LPS后60-120min降低,C、D、E组PBMC中NF-κB含量及血浆TNF-α浓度降低(P<0.05或0.01),但血浆IL-6浓度差异无统计学意义(P>0.05)。结论50mg·kg-1·h-1氯胺酮改善内毒血症大鼠血液动力学的紊乱,又可以在一定程度上抑制炎性反应,0.5、5mg·kg-1