局部麻醉药引起不可逆神经损伤的可能机制：局部麻醉药的去污剂特性与膜破坏
Possible mechanism of irreversible nerve injury caused by local anesthetics: detergent properties of local anesthetics and membrane disruption.
作者信息
Kitagawa Norihito, Oda Mayuko, Totoki Tadahide
机构信息
Department of Anesthesiology, Saga Medical School, Nabeshima, Saga, Japan.
出版信息
Anesthesiology. 2004 Apr;100(4):962-7. doi: 10.1097/00000542-200404000-00029.
BACKGROUND
Irreversible nerve injury may result from neural membrane lysis due to the detergent properties of local anesthetics. This study aimed to investigate whether local anesthetics display the same properties as detergents and whether they disrupt the model membrane at high concentrations.
METHODS
Concentrations at which dodecyltrimethylammonium chloride and four local anesthetic (dibucaine, tetracaine, lidocaine, and procaine) molecules exhibit self-aggregation in aqueous solutions were measured using an anesthetic cation-sensitive electrode. Light-scattering measurements in a model membrane solution were also performed at increasing drug concentrations. The concentration at which drugs caused membrane disruption was determined as the point at which scattering intensity decreased. Osmotic pressures of anesthetic agents at these concentrations were also determined.
RESULTS
Concentrations of dodecyltrimethylammonium chloride, dibucaine, tetracaine, lidocaine, and procaine at which aggregation occurred were 0.15, 0.6, 1.1, 5.3, and 7.6%, respectively. Drug concentrations causing membrane disruption were 0.09% (dodecyltrimethylammonium chloride), 0.5% (dibucaine), 1.0% (tetracaine), 5.0% (lidocaine), 10.2% (procaine), and 20% (glucose), and osmotic pressures at these concentrations were 278, 293, 329, 581, 728, and 1,868 mOsm/kg H2O, respectively.
CONCLUSIONS
These results show that all four local anesthetics form molecular aggregations in the same manner as dodecyltrimethylammonium chloride, a common surfactant. At osmotic pressures insufficient to affect the membrane, local anesthetics caused membrane disruption at the same concentrations at which molecular aggregation occurred. This shows that disruption of the model membrane results from the detergent nature of local anesthetics. Nerve membrane solubilization by highly concentrated local anesthetics may cause irreversible neural injury.
背景
局部麻醉药的去污剂特性可能导致神经膜溶解，进而引起不可逆的神经损伤。本研究旨在调查局部麻醉药是否具有与去污剂相同的特性，以及它们在高浓度时是否会破坏模型膜。
方法
使用麻醉阳离子敏感电极测量十二烷基三甲基氯化铵和四种局部麻醉药（丁卡因、地卡因、利多卡因和普鲁卡因）分子在水溶液中表现出自聚集的浓度。在模型膜溶液中，随着药物浓度的增加也进行了光散射测量。将药物导致膜破坏的浓度确定为散射强度降低的点。还测定了这些浓度下麻醉剂的渗透压。
结果
十二烷基三甲基氯化铵、丁卡因、地卡因、利多卡因和普鲁卡因发生聚集的浓度分别为0.15%、0.6%、1.1%、5.3%和7.6%。导致膜破坏的药物浓度分别为0.09%（十二烷基三甲基氯化铵）、0.5%（丁卡因）、1.0%（地卡因）、5.0%（利多卡因）、10.2%（普鲁卡因）和20%（葡萄糖），这些浓度下的渗透压分别为278、293、329、581、728和1868 mOsm/kg H₂O。
结论
这些结果表明，所有四种局部麻醉药都以与常见表面活性剂十二烷基三甲基氯化铵相同的方式形成分子聚集体。在渗透压不足以影响膜的情况下，局部麻醉药在发生分子聚集的相同浓度下导致膜破坏。这表明模型膜的破坏是由局部麻醉药的去污剂性质引起的。高浓度局部麻醉药使神经膜溶解可能会导致不可逆的神经损伤。
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