格列苯脲对丙泊酚、氯胺酮、依托咪酯及咪唑安定致兔离体气管平滑肌舒张作用的影响

目的：观察丙泊酚、氯胺酮、依托咪酯及咪唑安定对乙酰胆碱预处理的离体气管条的作用，并探讨该作用与ATP敏感性钾通道的关系。方法：采用离体气管条模型，首先观察丙泊酚、氯胺酮、依托咪酯及咪唑安定对乙酰胆碱预处理气管条肌张力的变化；然后用格列苯脲孵育，观察丙泊酚、氯胺酮、依托咪酯及咪唑安定对肌张力的影响。结果：丙泊酚、氯胺酮、依托咪酯及咪唑安定都可以舒张气管平滑肌，而用格列苯脲孵育后，可以部分阻断上述各药舒张气管平滑肌的效应（P＜0．01）。结论：丙泊酚、氯胺酮、依托咪酯及咪唑安定对离体气管平滑肌的舒张作用与ATP敏感性钾通道有关。     

依托咪酯配合芬太尼用于小儿气管异物取出术

依托咪酯配合芬太尼用于小儿气管异物取出术高凌，王金泉，袁振瑞，庞维新我院１９９０～１９９３年应用依托咪酯配合芬太尼用于小儿气管异物取出麻醉３０例，效果满意。资料与方法本组男２１例，女９例，年龄５～１５岁。异物种类：塑料笔帽、瓜子、花生及其它。异物部位...     

依托咪酯、异丙酚和硫喷妥钠插管后呼吸道阻力的比较

清醒病人或麻醉诱导气管插管,常引起支气管收缩和气道阻力增加,这可能是喉和气道感受器反射的激活所致。哮喘病人异丙酚诱导气管插管不引起哮喘发作,而用硫巴比妥诱导有27％发作,用羟巴比妥(oxybarbitrurate)则有13％发作。依托咪酯常被用于血流动力学不稳定或哮喘病人。 作者选择无肺部疾患、非心脏手术的全麻插管75例病人,随机选注硫喷妥钠(n=31),依托咪酯(n=23)     

依托咪酯配合芬太尼用于小儿气管异物麻醉观察

依托咪酯配合芬太尼用于小儿气管异物麻醉观察高凌，易桂云，庞维新，袁振瑞应用依托咪酯配合芬太尼用于小儿气管异物麻醉３０例，男２１例，女９例，年龄５～１５岁。术前３０ｍｉｎ肌注阿托品０；０ｌｍｇ／ｋｇ、氯丙嗪１ｍｇ／ｋｇ。由静脉先注入芬太尼２μｇ／ｋｇ，...     

老年和成年患者依托咪酯诱导时雷米芬太尼抑制气管插管反应的半数有效血浆浓度

目的测定老年和成年患者依托咪酯诱导时雷米芬太尼抑制气管插管反应的半数有效血浆浓度(Cp50)。方法择期全麻手术患者40例,ASAⅠ或Ⅱ级,年龄19~80岁,体重指数20~30kg/m2,按年龄分为青壮年组(19~64岁)和老年组(65~80岁),每组20例。雷米芬太尼靶控输注5min后,静脉注射0.3mg/kg的依托咪酯,患者意识消失后给予罗库溴铵行气管插管。雷米芬太尼的血浆靶浓度按序贯法确定,相邻血浆靶浓度之间的比率为1.2。结果0.3mg/kg依托咪酯诱导时,老年组和青壮年组雷米芬太尼抑制气管插管的Cp50分别为4.11μg/L和3.37μg/L,95%可信区间分别为3.90~4.34μg/L和3.02~3.75μg/L。结论老年和青壮年患者在复合0.3mg/kg的依托咪酯行麻醉诱导时,雷米芬太尼抑制气管插管反应的Cp50分别为4.11g/L和3.37μg/L。     

不同剂量依托咪酯麻醉诱导时瑞芬太尼抑制病人气管插管反应的半数有效血浆靶浓度

依托咪酯是临床常用短效静脉麻醉药,起效快、安全界限大、ED50/LD50.比值为26.4、清醒迅速、对呼吸无明显抑制、无术中知晓是其突出优点[1].瑞芬太尼是超短效μ受体激动剂,可抑制气管插管反应[2].本试验拟研究不同剂量依托咪酯麻醉诱导时瑞芬太尼抑制病人气管插管反应的半数有效血浆靶浓度(Cp50),为临床提供参考.     

依托咪酯对HL-60细胞的毒性作用及依托咪酯预处理对其的影响

目的探讨依托咪酯对人急性髓性细胞白血病细胞（HL-60细胞）的毒性作用,及依托咪酯预处理对此毒性作用的影响。方法实验分两部分,第一部分为细胞毒性实验,HL-60细胞随机分为6组,对照组不用依托咪酯处理,其他5组分别加入50、100、250、500、1 000μmol/L依托咪酯,每组分别作用4、8、12、24、48 h,进行下述指标检测。第二部分为预处理实验,HL-60细胞随机分为3组,对照组不用依托咪酯处理,依托咪酯组加入500μmol/L依托眯酯作用24 h,预处理组先加入1μmol/L依托咪酯作用1 h,洗脱后在培养基中孵育4 h,再加入500μmol/L依托咪酯作用24 h。采用MTT实验方法检测细胞活力,采用AnnexinⅤ-PI流式细胞仪检测细胞凋亡。结果依托咪酯可抑制HL-60细胞活力,诱导细胞凋亡,呈浓度和时间依赖性。1μmol/L依托咪酯预处理1 h,4 h后对500μmol/L依托咪酯作用24 h诱发的细胞凋亡具有抑制作用（P＜0．05）。结论依托咪酯通过诱发细胞凋亡,对HL-60细胞的功能产生了抑制作用,1μmol/L依托咪酯刺激1 h预处理可减轻药物自身引起的这种抑制作用。     

不同麻醉诱导药对血钾浓度变化及肌颤和肌痛的影响

目的 观察硫喷妥钠、咪唑安定、依托咪酯以及异丙酚麻醉诱导对琥珀胆碱引起的血钾升高、肌颤和肌痛的影响。方法 ＡＳＡⅠ～Ⅱ级病人６０例,随机分为四组,分别采用硫喷妥钠、咪唑安定、依托咪酯或异丙酚静脉诱导,静注琥珀胆碱后行气管插管。于诱导前、气管插管前和插管后测定血清钾浓度,并观察诱导期病人肌颤及术后病人肌痛的发生率。结果 各组病人诱导前及气管插管前的血钾浓度组间及组内比较均无显著差异（Ｐ〉０．０５）,     

依托咪酯对大鼠海马脑片突触长时程增强的影响

目的 评价依托咪酯对大鼠海马脑片突触长时程增强(LTP)的影响.方法 雄性SD大鼠,断头后取出海马组织,制备厚400 μm的海马脑片.采用细胞外微电极记录技术,记录海马脑片CA1区细胞外群体峰电位(PS).取42张脑片,随机分为6组(n=7):用正常的人工脑脊液(ACSF)灌流海马脑片记录正常的PS,待其稳定后,对照组继续灌流ACSF,不同浓度依托咪酯组分别用含依托咪酯1μmol/L(依托咪酯 1 μol/L组)、2/μmol/L(依托咪酯2 μmol/L组)、5 μmol/L(依托咪酯5 μmol/L组)、10μmol/L(依托咪酯10 μmol/L组)、20 μmol/L(依托咪酯20 μmol/L组)的ACSF灌流,记录PS幅值.另取84张脑片,随机分为12组(n=7):用正常ACSF灌流海马脑片,记录稳定正常的PS 30 min,LIT组继续灌流ACSF,其余各组分别用含依托咪酯l μmol/L(LTP-依托咪酯 1 μmol/L组)、2 μmol/L(LTP-依托咪酯2μmol/L组)、5 μmol/L(LTP-依托咪酯 5 μmol/L组)、10μmol/L(LTP-依托咪酯 10 μmol/L组)、20 μmol/L(LTP-依托咪酯20 μmol/L组)、印防己毒素50 μmol/L(印防己毒素组)、荷包牡丹碱10 μmol/L(荷包牡丹碱组)、CGP35348 5 μmol/L(CGP35348 组)、印防己毒素50 μmol/L+依托咪酯10 μmol/L(印防己毒素+依托咪酯组)、荷包牡丹碱10 μmol/L+依托咪酯10 μmol/L(荷包牡丹碱+依托咪酯组)、CGP35348 5 μmol/L+依托咪酯10 μmol/L(CGP35348+依托咪酯组)的ASCF灌流,记录PS 30 min后,施以100 Hz的高频刺激(HPS),记录PS幅值.结果 与LTP组比较,LTP-依托咪酯2 μmol/L组、LTP-依托咪酯5 μmol/L组、LTP-依托咪酯10 μmol/L组、LTP-依托咪酯20 μmol/L组和CGP35348+依托咪酯组HIS后PS幅值降低(P＜0.05或0.01),印防己毒素组、荷包牡丹碱组、CGP35348组HFS后PS幅值差异无统计学意义(P＞0.05);与依托咪酯LTP 10μmol/L组比较,印防己毒素+依托咪酯组和荷包牡丹碱+依托咪酯组HIS后PS幅值增加(P＜0.01).结论 依托咪酯可通过激活大鼠海马GABAA受体抑制LTP的形成,从而影响学习和记忆功能.     

静脉麻醉药对离体气道平滑肌的影响

静脉麻醉药对气道平滑肌的影响是临床工作常应考虑的重要问题。尽管对硫喷妥钠(Sp)和氯胺酮(Ket)的作用已成定论,但异丙酚(P)及依托咪酯(E)的影响尚无肯定。本文作者旨在比较研究Sp、P与E对离体气道平滑肌的影响,并试图阐述其机制。 选择FEV_1>80％的肺癌手术病人切下之病肺置于K-H保存液中,在显微镜下选取非肿瘤所在区域的3～4级支气管,将其切成支气管环备用。另选择10～15周龄Wistar大鼠,取其气管背侧的肌束,去除上皮细胞后切成1mm×1mm大小的碎片,在低钙生理盐水中孵育。应用乙酰胆碱(Ach)的作用作为支气管收缩程度的效应指标。将人离体支气管环被动免疫致敏并观察在加入不同浓度P、E后对组织胺(His)的反应。荧光     

异丙酚对兔离体气管平滑肌收缩力的影响

目的 探讨异丙酚对气管平滑肌的直接影响,为有气管高反应患者临床选择用药提供实验参考依据。方法 采用电刺激兔离体气管平滑肌的方法研究异丙酚对其的影响。结果 10^-4mol/L的异丙酚可使电刺激诱发的兔离体气管平滑肌收缩力下降21．6％,10^-2mol/L的异丙酚可使电刺激诱发的兔离体气管平同收缩力下降35．4％。结论 异丙酚有舒张兔离体气管平滑肌的作用。     

异丙嗪逆转管箭毒对电场刺激引起的离体兔气管平滑肌收缩效应

管箭毒0.6mg·100ml~(-1),增强兔气管平滑肌对电场刺激引起的收缩效应(P<0.01),在管箭毒溶液中加入异丙嗪1mg·100ml~(-1),管箭毒增强气管平滑肌对电场刺激引起的收缩效应即被逆转,并且收缩力降至对照值以下,表明异雨嗪不仅有效地逆转管箭毒增强兔气管平滑肌对电场刺激引起的收缩效应,并可使其进一步减低,提示气道高反应性病人需要用管箭毒时可事先用异丙嗪预防可能发生的支气管痉挛,管箭毒导致的支气管痉挛可试用异雨嗪处理。     

Local anaesthetics inhibit cholinergic and non-cholinergic neural and muscular contractions in avian tracheal smooth muscle

The effects of five different local anaesthetics: lignocaine, prilocaine, etidocaine, mepivacaine, bupivacaine, on tone, contractility, and on cholinergic and non-cholinergic responses of chick tracheal smooth muscle were studied and compared in vitro. The cholinergic and non-cholinergic contractions of the tracheal smooth muscle were elicited by electrical field stimulation, at a maximal voltage with 0.2 Hz and 0.2 ms square pulse duration, in the presence of adrenergic blockers, guanethidine, propranolol, and other drugs, e.g. indomethacin. Atropine was used to reduce the cholinergic responses due to electrical field stimulation and to applied acetylcholine (ACh). Lignocaine, in low concentrations, reduced these responses and also those produced by electrical field stimulation in the presence of atropine. In high concentration (greater than 100 times clinical concentrations), lignocaine abolished all the responses and produced a sustained contracture in the muscle. Among the local anaesthetics studied, bupivacaine and lignocaine were found to be more effective than mepivacaine, prilocaine and etidocaine, in reducing the cholinergic contractions produced by electrical field stimulation and by exogenous ACh. It was suggested that lignocaine, and other local anaesthetic drugs, may have an anti-spasmic effect on the tracheal smooth muscle, in that they inhibited the contractions induced by electrical field stimulation and by depolarizing agents.     

Different inhibitory effects of volatile anesthetics on T- and L-type voltage-dependent Ca2+ channels in porcine tracheal and bronchial smooth muscles

BACKGROUND: The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs). METHODS: Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution. RESULTS: The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (approximately 30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle. CONCLUSIONS: The existence of the T-type VDC in bronchial smooth muscle and the high sensitivity of this channel to volatile anesthetics seem to be, at least in part, responsible for the different reactivities to the anesthetics in tracheal and bronchial smooth muscles.     

Different Inhibitory Effects of Volatile Anesthetics on T- and L-type Voltage-dependent Ca2+ Channels in Porcine Tracheal and Bronchial Smooth Muscles

Background: The distal airway is more important in the regulation of airflow resistance than is the proximal airway, and volatile anesthetics have a greater inhibitory effect on distal airway muscle tone. The authors investigated the different reactivities of airway smooth muscles to volatile anesthetics by measuring porcine tracheal or bronchial (third to fifth generation) smooth muscle tension and intracellular concentration of free Ca2+ ([Ca2+]i) and by measuring inward Ca2+ currents (ICa) through voltage-dependent Ca2+ channels (VDCs).

Methods: Intracellular concentration of free Ca2+ was monitored by the 500-nm light emission ratio of Ca2+ indicator fura-2. Isometric tension was measured simultaneously. Whole-cell patch clamp recording techniques were used to investigate the effects of volatile anesthetics on ICa in dispersed smooth muscle cells. Isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) was introduced into a bath solution.

Results: The volatile anesthetics tested had greater inhibitory effects on carbachol-induced bronchial smooth muscle contraction than on tracheal smooth muscle contraction. These inhibitory effects by the anesthetics on muscle tension were parallel to the inhibitory effects on [Ca2+]i. Although tracheal smooth muscle cells had only L-type VDCs, some bronchial smooth muscle cells (~30%) included T-type VDC. Each of the two anesthetics significantly inhibited the activities of both types of VDCs in a dose-dependent manner; however, the anesthetics had greater inhibitory effects on T-type VDC activity in bronchial smooth muscle.     

Effects of sodium metabisulphite on guinea pig contractile airway smooth muscle responses in vitro.

BACKGROUND--Sodium metabisulphite (MBS) is known to induce bronchoconstriction in asthmatic patients. The effects of MBS on guinea pig airway smooth muscle and on neurally mediated contraction in vitro have been examined. METHODS--Tracheal and bronchial airway segments were placed in oxygenated buffer solution and electrical field stimulation was performed in the presence of indomethacin (10(-5) M) and propranolol (10(-6) M) for the measurement of isometric tension. Atropine (10(-6) M) was added to bronchial tissues. RESULTS--Concentrations of MBS up to 10(-3) M had no direct effect on airway smooth muscle contraction and did not alter either tracheal smooth muscle contraction induced by electrical field stimulation at all frequencies or acetylcholine-induced tracheal smooth muscle contraction. There was a similar response in the absence of epithelium, except for potentiation of the response induced by electrical field stimulation at 0.5 Hz (24 (10)% increase). However, MBS (10(-5), 10(-6) and 10(-7) M) augmented neurally-mediated non-adrenergic non-cholinergic contractile responses in the bronchi (13.3 (3.2)%, 23.8 (9.6)%, and 6.4 (1.6)%, respectively). MBS had no effect on the contractile response induced by substance P, but at higher concentrations (10(-3) M and 10(-4) M) it caused a time-dependent attenuation of responses induced by either electrical field stimulation or exogenously applied acetylcholine or substance P. CONCLUSIONS--MBS had no direct contractile responses but enhanced bronchoconstriction induced by activation of non-cholinergic neural pathways in the bronchus, probably through increased release of neuropeptides. At high concentrations MBS inhibited contractile responses initiated by receptor or neural stimulation.     

Effects of Intravenous Anesthetics on Normal and Passively Sensitized Human Isolated Airway Smooth Muscle

Background: General anesthetics may modify airway responsiveness. The authors investigated the effect of thiopental, propofol, and etomidate on airway smooth muscle.

Methods: Contraction experiments were done in human airway rings that were either normal or passively sensitized with asthmatic serum. The effect of propofol and etomidate was also studied on both [Ca sup +] sub i increase measured by microspectrofluorimetry in isolated myocytes and isometric contraction in the rat trachea.

Results: In human bronchi, thiopental (10 sup -7 to 10 sup -4 M) induced a concentration-dependent contraction. Neither propofol nor etomidate altered baseline tone, but both anesthetics reduced histamine-induced contraction. In human immunologically sensitized isolated bronchi, propofol (3 x 10 sup -4 M) reduced histamine reactivity (Delta Fmax in %) to a greater degree than in nonsensitized tissues (64.4 +/- 15.7% and 16.4 +/- 8.5%, respectively; n = 6, P < 0.05), whereas the effect of etomidate (10 sup -4 M) was similar in both types of tissue (24.1 +/- 6% and 22.3 +/- 15%, respectively, n = 6). In rat isolated tracheal myocytes, propofol (3 x 10 sup -4 M) and etomidate (10 sup -4 M) altered the [Ca2+]i signal in response to the depolarizing agent potassium chloride and the muscarinic agonist acetylcholine. Accordingly, the two anesthetics also reduced the mechanical response of rat tracheal rings to these agonists.     

The effects of propofol and etomidate on airway contractility in chronically hypoxic rats

We investigated the effect of two IV anesthetics, propofol and etomidate, on airway responsiveness in a rat model of chronic hypoxia (CH) in comparison with normoxic rats. CH rats were obtained using a hypobaric chamber (14 days at a barometric pressure of 380 mm Hg). The ability of both anesthetics to relax and prevent agonist-induced contraction was assessed in isolated tracheal rings precontracted with the muscarinic agonist carbachol (CCh) and the depolarizing agent KCl. Cumulative concentrations of both compounds relaxed tracheal rings precontracted with CCh or KCl with a similar amplitude in CH and normoxic rats. In tracheal rings precontracted with CCh, the negative logarithm of anesthetics that reduced the maximal contraction by 30%, i.e., -log half-maximal inhibitory concentration, for propofol and etomidate were 4.10 +/- 0.09 and 4.12 +/- 0.15 in normoxic rats and 4.20 +/- 0.22 and 3.61 +/- 0.19 in CH rats, respectively. At a fixed concentration, propofol (3 x 10(-4) M) or etomidate (10(-4) M) also inhibited CH tracheal rings contraction in response to cumulative concentrations of CCh and KCl. However, in contrast with the equivalent relaxant effect of both anesthetics, etomidate was two-fold less effective than propofol for inhibiting the subsequent contraction to CCh and KCl. These results indicate that propofol and etomidate retain their relaxant properties in CH rat airways by acting on the pharmaco- and electromechanical coupling. IMPLICATIONS: Anesthesia may cause airway constriction or bronchospasm in patients with normal or pathological airways. This study investigated the ability of propofol and etomidate to both reverse precontraction and inhibit contraction of tracheal rings isolated from chronically hypoxic rats.     

Effects of intravenous anesthetics on Ca2+ sensitivity in canine tracheal smooth muscle

BACKGROUND: Halothane and other volatile anesthetics relax airway smooth muscle in part by decreasing the amount of force produced for a particular intracellular calcium concentration (the Ca2+ sensitivity) during muscarinic receptor stimulation. In this study, ketamine, propofol, and midazolam were evaluated to determine whether the inhibitory effect of volatile anesthetics on this signal transduction pathway is a general property of other types of anesthetic drugs. METHODS: A beta-escin permeabilized canine tracheal smooth muscle preparation was used. Ketamine, propofol, and midazolam, in concentrations producing near-maximal relaxation in intact airway smooth muscle (200 microM, 270 microM, and 100 microM, respectively), were applied to permeabilized muscles stimulated with calcium in either the absence or the presence of muscarinic receptor stimulation provided by acetylcholine. The effect of halothane also was evaluated. RESULTS: Confirming previous studies, halothane (0.75 mM) decreased calcium sensitivity during muscarinic receptor stimulation. None of the intravenous anesthetics studied affected Ca2+ sensitivity, either in the absence or the presence of muscarinic receptor stimulation. CONCLUSIONS: Intravenous anesthetics in high concentrations directly relax canine tracheal smooth muscle without affecting Ca2+ sensitivity. The inhibition of agonist-induced increases in Ca2+ sensitivity of canine tracheal smooth is not a common property of anesthetics, but is unique to volatile agents.     

Differential effects of halothane on airway nerves and muscle

Effects of halothane on the excitation-contraction coupling or neuro-effector transmission in the dog tracheal muscle were observed in vitro in an attempt to clarify the cellular mechanisms involved in anesthetic-induced bronchodilation. Double sucrose gap, microelectrode, and tension recording methods were used. Application of halothane evoked an initial induction of phasic contraction with no alteration in the electrical membrane properties, and secondarily a reduction in muscle tone with membrane hyperpolarization. Halothane suppressed the amplitude of the twitch contractions evoked by indirect (nerve mediated) or direct muscle stimulation, the degree of suppression being greater with the former stimulation. The threshold membrane depolarization required for the generation of tension development was increased. In the presence or absence of TEA, halothane completely suppressed the generation of an action potential or a local response in the muscle membrane, following stimulation by outward current pulses. Therefore, halothane has complex actions on Ca++ economy in the tracheal smooth muscle cell, i.e., initial release of Ca++ from the store sites followed by inactivation or a reduction in free calcium ions in the cytoplasm, and/or suppression of the influx of Ca++ across the cell membrane. Low concentrations of halothane (less than or equal to 1%) suppressed the amplitude of excitatory junction potential (EJP) without altering the membrane potential, membrane resistance, or muscle sensitivity to acetylcholine. Therefore, this anesthetic probably suppresses the release of transmitter from the nerve terminals. Halothane also suppressed the facilitation phenomena of EJP during repetitive nerve stimulation. These direct inhibitory effects of halothane on smooth muscle cells and excitatory neuro-effector transmission could account for the potent bronchodilator action of this anesthetic.