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2002 Fiscal Year Final Research Report Summary

Mechanism of Local Anesthetic Neurotoxicity and Detection of the Toxic Concentration

Research Project

Project/Area Number 12671478
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionSaga Medical School

Principal Investigator

KITAGAWA Norihito  Saga Medical School Department of Anesthesia, Assistant Professor, 医学部, 講師 (90177832)

Project Period (FY) 2000 – 2002
Keywordslocal anesthetics / neurotoxicity / solbilization / micelle / current perception threshold / spinal anesthesia / hemolysis
Research Abstract

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

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 北川範仁, 小田万友子, 十時忠秀: "局所麻酔薬に関する最近の知見"麻酔. 50. S71-S81 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川範仁, 小田万友子, 桜田琢, 楊邦祥, 十時忠秀, 森本正敏: "ニューロメータによるクモ膜下リドカイン投与後の神経損傷の評価"麻酔. 50. 453 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川範仁, 小田万友子, 十時忠秀: "局所麻酔薬の神経毒性"Life Support and Anesthesia. 10(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Norihito Kitagawa, Mayuko Oda, Tadahide Totoki: "Neurotoxicity of Local Anesthetics"Life Support and Anesthesia. vol.10 (In Press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Norihito Kitagawa, Mayuko Oda, Tadahide Totoki, Nobutaka I, Masatoshi Morimoto: "Correlation between Hemolytic Potency and Neurotoxicity of Local Anesthetics"Anesthesiology. A735. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mayuko Oda, Norihito Kitagawa, Taku Sakurada, Tadahide Totoki, Masatoshi Morimoto: "Immunohistochemical Evaluation of Local Anesthetic Neurotoxicity in Rats"Anesthesiology. A-907. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Oda, N. Kitagawa, T. Sakurada, T. Miyabe, T. Totoki, M. Morimoto: "Is the Neurotoxic Concentration Predicted from Solution Property of Local Anesthetics Agreement with that Obtained from Animal Study?"Regional Anesthesia and Pain medicine. PD-27. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M. Oda, N. Kitagawa, T. Miyabe, A. Miyazaki, T. Totoki, M. Morimoto: "Quantitative Evaluation of Lidocaine Neurotoxicity by Current Perception Threshold Testing in Rats"Regional Anesthesia and Pain medicine. PD-33. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N. Kitagawa, M. Oda, T. Sakurada, T. Miyabe, T. Totoki, T. Hotokebuchi: "Does Intrathecal Morphine Have Advantage In Postoperative Pain Relief After Total Hip Arthroplasty?"Regional Anesthesia and Pain medicine. PE-69. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Norihito Kitagawa, Mayuko Oda, Tadahide Totoki: "Current Review of Local Anesthetics"Masui. 50. S71-81 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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