LOCAL ANESTHETIC NEUROTOXICITY IN THE SPINAL CORD

局部麻醉剂对脊髓的神经毒性

基本信息

项目摘要

The administration of epidural doses of the local anesthetic NESACAINE-CE (2-chloroprocaine) was the common factor in recent reports of long-lasting neurological deficits following regional anesthesia. Subsequent reviews of the clinical literature as well as numerous experimental studies have failed to discriminate if nerve injury should be attributed to some or all local anesthetics, the NESACAINE antioxidant, or the inadvertent administration of large epidural doses into the spinal cord subarachnoid space. It is not possible to explain these inconsistencies in the absence of information about the mechanisms of the observed injury. Using a rat sciatic nerve model, the applicant has demonstrated that local anesthetic-induced peripheral nerve injury is mediated by an initial increase in permeability of the perineurial sheath, followed by decreased nerve blood flow, dilution of normally hypertonic endoneurial fluid, increased endoneurial fluid pressure, injury of Schwann cells, and nerve fiber injury. In spinal cord the possible interactions between altered permeability of barrier systems, injury-induced fluid accumulation, and changes in interstitial fluid chemistry have not been considered previously for any model of central nervous system toxicity; therefore, it is important that studies in the sciatic nerve be extended to test the hypothesis that spinal cord toxicity following local anesthetic administration is mediated by changes in the interstitial environment affecting both structure and function. Specifically, neurological injury might be secondary to alterations in protective barrier systems and a compromise of nutritive blood flow. Commercial local anesthetic preparations will first be tested using quantitative measures of electrophysiological function in order to determine the relative toxicity of the epidural and subarachnoid routes of administration. Nerve conduction velocity and refractory periods will be determined for both dorsal roots and microfilaments. Using this model of functional deficit, the toxicity of local anesthetics, drug vehicles, and injection volume will be tested. Subsequent experiments will provide functional and structural evidence for corresponding changes in nerve fibers, the dura mater barrier, spinal cord blood flow, and interstitial fluid. These experiments will quantify changes in barrier permeability (penetration of horseradish peroxidase), blood flow (measured with a diffusible tracer), endoneurial fluid electrolytes (visualized with energy dispersive x-ray spectrometry), and fluid pressure.
硬膜外剂量局麻药NESACAINE-CE的应用 (2-氯普鲁卡因)是最近报道的长期持续的共同因素 区域麻醉后的神经功能障碍。随后对以下内容进行审查 临床文献以及大量的实验研究都表明 未能区分神经损伤是否应归因于部分或全部 局麻药,NESACAINE抗氧化剂,或无意中 大剂量硬膜外注射入脊髓蛛网膜下腔 太空。在缺席的情况下,无法解释这些不一致之处 关于观察到的损伤机制的信息。 使用大鼠坐骨神经模型,申请人已经证明了局部 麻醉诱导的周围神经损伤是由最初的 神经鞘通透性增加,随后降低 神经血流,稀释正常的高渗神经内膜液, 神经内液压力升高、雪旺细胞和神经损伤 纤维损伤。在脊髓中,改变之间可能的相互作用 屏障系统的渗透性、损伤引起的液体堆积以及 间质液体化学的变化以前没有被考虑过 任何模型的中枢神经系统毒性;因此,它是 重要的是要扩大对坐骨神经的研究,以测试 局麻药致脊髓毒性假说 给药是由间质环境的变化调节的 同时影响结构和功能的。具体地说,神经损伤 可能是次要的,因为防护屏障系统和 营养血流受损。 商业局部麻醉制剂将首先进行测试,使用 电生理功能的定量测量 测定硬膜外途径和蛛网膜下腔途径的相对毒性 行政管理。神经传导速度和不应期 对背根和微丝都有测定。使用此模型 功能缺陷,局麻药,药物载体的毒性,以及 将测试注射体积。随后的实验将提供 神经相应变化的功能和结构证据 纤维、硬脑膜屏障、脊髓血流量和间质 流体。这些实验将量化屏障渗透性的变化。 (辣根过氧化物酶的穿透),血流量(用 可扩散示踪剂),神经内液电解质(用能量可视化 色散X射线光谱分析)和流体压力。

项目成果

期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Permeability and surface area of the blood-nerve barrier in galactose intoxication.
半乳糖中毒时血神经屏障的渗透性和表面积。
  • DOI:
    10.1016/0006-8993(93)90434-o
  • 发表时间:
    1993
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    Mizisin,AP;Kalichman,MW
  • 通讯作者:
    Kalichman,MW
Effects of cocaine on blood flow and prostaglandin metabolites in rat sciatic nerve.
可卡因对大鼠坐骨神经血流和前列腺素代谢的影响。
  • DOI:
    10.1152/ajpheart.1994.266.6.h2515
  • 发表时间:
    1994
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Kalichman,MW;Sanicolas,MT;Jorge,MC;Roux,L
  • 通讯作者:
    Roux,L
Physiologic Mechanisms by Which Local Anesthetics May Cause Injury to Nerve and Spinal Cord
局部麻醉药可能导致神经和脊髓损伤的生理机制
Quantitative histologic analysis of local anesthetic-induced injury to rat sciatic nerve.
局麻药所致大鼠坐骨神经损伤的定量组织学分析。
Effects of aging on nerve conduction block induced by bupivacaine and procaine in rats.
衰老对布比卡因和普鲁卡因引起的大鼠神经传导阻滞的影响。
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MICHAEL W KALICHMAN其他文献

MICHAEL W KALICHMAN的其他文献

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{{ truncateString('MICHAEL W KALICHMAN', 18)}}的其他基金

Characterizing Privacy Perceptions and Risks in HIV Molecular Epidemiology
HIV 分子流行病学中的隐私认知和风险特征
  • 批准号:
    8789729
  • 财政年份:
    2014
  • 资助金额:
    $ 7.8万
  • 项目类别:
Standards of Scientific Conduct
科学行为标准
  • 批准号:
    7491756
  • 财政年份:
    2007
  • 资助金额:
    $ 7.8万
  • 项目类别:
Standards of Scientific Conduct
科学行为标准
  • 批准号:
    7288429
  • 财政年份:
    2007
  • 资助金额:
    $ 7.8万
  • 项目类别:
TRAINING IN CLINICAL RESEARCH ETHICS
临床研究伦理培训
  • 批准号:
    6923932
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
TRAINING IN CLINICAL RESEARCH ETHICS
临床研究伦理培训
  • 批准号:
    6532603
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
TRAINING IN CLINICAL RESEARCH ETHICS
临床研究伦理培训
  • 批准号:
    6615627
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
TRAINING IN CLINICAL RESEARCH ETHICS
临床研究伦理培训
  • 批准号:
    6286155
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
TRAINING IN CLINICAL RESEARCH ETHICS
临床研究伦理培训
  • 批准号:
    6775719
  • 财政年份:
    2001
  • 资助金额:
    $ 7.8万
  • 项目类别:
LOCAL ANESTHETIC NEUROTOXICITY IN THE SPINAL CORD
局部麻醉剂对脊髓的神经毒性
  • 批准号:
    3476889
  • 财政年份:
    1987
  • 资助金额:
    $ 7.8万
  • 项目类别:
LOCAL ANESTHETIC NEUROTOXICITY IN THE SPINAL CORD
局部麻醉剂对脊髓的神经毒性
  • 批准号:
    3476888
  • 财政年份:
    1987
  • 资助金额:
    $ 7.8万
  • 项目类别:

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