Mechanism of Local Anesthetic Neurotoxicity and Detection of the Toxic Concentration

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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