LOCAL ANESTHETIC NEUROTOXICITY IN THE SPINAL CORD
局部麻醉剂对脊髓的神经毒性
基本信息
- 批准号:3476892
- 负责人:
- 金额:$ 7.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1987
- 资助国家:美国
- 起止时间:1987-04-01 至 1993-06-30
- 项目状态:已结题
- 来源:
- 关键词:Schwann cells X ray spectrometry anesthesia complication antioxidants autoradiography cerebrospinal fluid pressure drug administration routes electrophysiology epidural anesthesia histopathology laboratory rat local anesthetics membrane permeability neural conduction neuropharmacology neurotoxins peripheral nervous system peripheral nervous system disorders radiotracer subarachnoid space
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.
硬膜外给药局麻药NESACAINE-CE
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
- DOI:10.1136/rapm-00115550-199318061-00012
- 发表时间:1993
- 期刊:
- 影响因子:5.1
- 作者:M. Kalichman
- 通讯作者:M. Kalichman
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。
- DOI:
- 发表时间:1989
- 期刊:
- 影响因子:0
- 作者:Kalichman,MW;Powell,HC;Myers,RR
- 通讯作者:Myers,RR
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。
- DOI:
- 发表时间:1997
- 期刊:
- 影响因子:0
- 作者:Yee,TC;Kalichman,MW
- 通讯作者:Kalichman,MW
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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:
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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