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Mechanism of Local Anesthetic Neurotoxicity and Detection of the Toxic Concentration

局麻药神经毒性机制及毒性浓度检测

基本信息

批准号：
12671478
负责人：
KITAGAWA Norihito
金额：
$ 2.05万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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

我们主张高浓度局麻药引起的不可逆神经损伤是由于局麻药的增溶作用引起神经膜的破坏，并通过研究证明了这一点。1)我们证明了临床上使用的局麻药作为一种典型的洗涤剂在高浓度时形成了分子自聚集，这一结果证明了局麻药与普通表面活性剂具有相同的特性。2)通过测量局麻药与局麻药混合分散膜中的光散射，我们得到了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去污性破坏了膜。3)我们研究了模型膜被破坏的局麻药浓度是否会对大鼠产生不可逆神经损伤。《…的浓度》此外，鞘内注射地布卡因和利多卡因导致的不可逆神经功能障碍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，即高浓度局麻药诱导的不可逆神经损伤是由于局麻药增溶作用导致神经膜破裂所致。4)与传统方法相比，我们使用小口径导管(31G)建立了鞘内置管脊髓麻醉的新模型大鼠。5)我们首次应用神经纤维计对利多卡因诱导的大鼠神经损伤进行了评估，并证明该装置的评估优于传统方法。6)我们证明麻醉剂诱导的溶血浓度与动物实验获得的神经毒性浓度具有良好的一致性。我们的结果证实了局麻药所致的神经损伤是由麻醉剂引起的膜破裂所致。该溶血研究系统为解决局麻药神经毒性的机制提供了一个简单而基本的模型。较少