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乳化异氟醚抑制电压门控钠离子通道可能有助于其在比格犬中的蛛网膜下腔麻醉作用。

Inhibition of voltage-gated sodium channels by emulsified isoflurane may contribute to its subarachnoid anesthetic effect in beagle dogs.

机构信息

Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

出版信息

Reg Anesth Pain Med. 2011 Nov-Dec;36(6):553-9. doi: 10.1097/AAP.0b013e3182324d18.

DOI:10.1097/AAP.0b013e3182324d18
PMID:21989153
Abstract

BACKGROUND

Volatile anesthetics, in addition to their general anesthesia action, have been proven to produce regional anesthetic effect in various animal models. The major aim of this study was to examine whether emulsified isoflurane (EI) could also produce subarachnoid anesthesia and to investigate its possible mechanism.

METHODS

Beagle dogs were randomly assigned into 5 groups (n = 6/group): intrathecally receiving 1% lidocaine 0.1 mL/kg, 30% intralipid 0.1 mL/kg (control), or 8% EI at doses of 0.05, 0.075, or 0.1 mL/kg, respectively. Consciousness state, motor function of limbs, and response to nociceptive stimulus were observed after drug administration. The effect of EI on voltage-gated Na channel was recorded from isolated spinal neurons of rats, using the whole-cell patch-clamp technique. Inhibition of peak sodium currents and effect of EI on Na channel gating were analyzed.

RESULTS

Emulsified isoflurane produced subarachnoid anesthesia in a dose-dependent manner, and at the dose of 0.1 mL/kg, the effect of 8% EI was similar to 1% lidocaine. Sodium channel currents were inhibited by EI at clinically relevant concentrations, with the IC50 (median inhibitory concentration) at 0.69 ± 0.08 mM. Voltage activation of Na channels was positive, shifted by isoflurane at the concentration of 0.77 mM, and V½ of activation (voltage for half-maximal activation) shifted from -12.4 ± 2.7 mV to -7.3 ± 2.3 mV (P < 0.01).

CONCLUSIONS

Emulsified isoflurane produced dose-dependent subarachnoid anesthesia, and this effect might be mediated by inhibition of EI on voltage-gated Na channels in the spinal cord.

摘要

背景

挥发性麻醉剂除了具有全身麻醉作用外,已被证明在各种动物模型中具有局部麻醉作用。本研究的主要目的是检验乳化异氟醚(EI)是否也能产生蛛网膜下腔麻醉,并探讨其可能的机制。

方法

将比格犬随机分为 5 组(每组 6 只):鞘内给予 1%利多卡因 0.1 mL/kg、30%脂肪乳 0.1 mL/kg(对照组)或 8%EI 剂量分别为 0.05、0.075 或 0.1 mL/kg。给药后观察意识状态、四肢运动功能和痛觉刺激反应。采用全细胞膜片钳技术从大鼠分离的脊髓神经元记录 EI 对电压门控 Na 通道的作用。分析 EI 对峰值钠电流的抑制作用和对 Na 通道门控的影响。

结果

EI 呈剂量依赖性产生蛛网膜下腔麻醉,在 0.1 mL/kg 剂量下,8%EI 的作用与 1%利多卡因相似。EI 在临床相关浓度下抑制钠通道电流,IC50(中位数抑制浓度)为 0.69±0.08 mM。Na 通道的电压激活呈正相,异氟醚在 0.77 mM 浓度下发生移位,激活的 V½(半数最大激活电压)从-12.4±2.7 mV 移至-7.3±2.3 mV(P<0.01)。

结论

乳化异氟醚产生剂量依赖性蛛网膜下腔麻醉,这种作用可能是通过 EI 抑制脊髓中的电压门控 Na 通道介导的。

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