Mechanism of Local Anesthetic Neurotoxicity and Detection of the Toxic Concentration

我们认为高浓度局麻药引起的不可逆神经损伤是由局麻药增溶作用引起的神经膜破坏引起的，并对此进行了研究。1)我们发现临床上使用的局麻药与典型的洗涤剂一样，在高浓度下形成分子自聚集，这表明局麻药与常见的表面活性剂具有相同的特性。2)通过测量混合局麻药的膜分散液中的光散射，得到局麻药破坏磷脂模型膜的浓度。这些浓度与临界胶束浓度相同。这一结果表明，高浓度局麻药的洗涤剂性质破坏了膜。3)研究局麻浓度下大鼠是否发生不可逆神经损伤，破坏模型膜。二布卡因和利多卡因鞘内注射引起不可逆神经功能缺损的浓度几乎等于局部麻醉剂破坏模型膜的临界浓度。这一结果证实了我们的假设，即高浓度局麻药引起的不可逆神经损伤是由局麻药增溶作用引起的神经膜破坏引起的。4)采用小口径导管（31G），建立了新型脊髓麻醉大鼠鞘内置管与常规方法相比脊髓损伤较小的模型。5)我们首次应用神经计对利多卡因致大鼠神经损伤进行了评估，结果表明该仪器的评估结果优于传统仪器。6)我们证明了麻醉诱导的溶血浓度与动物实验中获得的神经毒性浓度很好地一致。我们的研究结果证实，局部麻醉引起的神经损伤是由麻醉引起的膜破坏引起的。这个溶血研究系统似乎是解决局麻神经毒性机制的一个简单和基本的模型。少

We advocated that an irreversible neural injury induced by highly concentrated local anesthetics resulted from neural membrane disruption caused by local anesthetic solubilizing action, and investigated to prove it.1) We showed that local anesthetics clinically used formed the molecular self-aggregation at high concentration as a typical detergent did This result demonstrated that local anesthetics had same characteristics with a common surfactant.2) From the measurement of light scattering in the membrane dispersion mixed with local anesthetics, we obtained the concentration at which local anesthetics disrupted the phospholipid model membrane. Those concentrations were identical to those of critical micellar concentration. This result demonstrated that the detergent nature of highly concentrated local anesthetics disrupted the membrane.3) We studied whether a irreversible neural injury in rat occur at local anesthetic concentration that model membrane was disrupted. The concentrations … More at which dibucaine and lidocaine intrathecally administered caused irreversible neurological deficits were almost equal to critical concentrations at which model membrane was disrupted by local anesthetics. This result confirmed our hypothesis that an irreversible neural injury induced by highly concentrated local anesthetics resulted from neural membrane disruption caused by local anesthetic solubilizing action.4) By using small bore catheter (31G), we developed the new model rat for spinal anesthesia with less spinal injury at an intrathecal catheter implantation comparing to conventional method.5) We firstly applied a neurometer to a assessment of neurological injury in rat induced by lidocaine, and demonstrated that the assessment by this device war superior then that by conventional one.6) We demonstrated that anesthetic-induced hemolysis concentrations were good agreement with their neurotoxic concentrations accessed by animal study. Our results confirm that local anesthetic- induced nerve injury come from membrane disruption caused by anesthetic. This hemolysis study system appears to be a simple and basic model for resolving the mechanism of local anesthetic neurotoxicity. Less