Comparative Neurotoxicity of Stereoisomers and Racemic Bupivacaine Administered Intrathecally in the Rat

立体异构体和外消旋布比卡因鞘内给药对大鼠的神经毒性比较

• 批准号: 12671483
• 负责人: TANIGUCHI Masahiko
• 金额: $ 2.05万
• 依托单位: 宮崎医科大学
• 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 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671483/
• 关键词: local anesthetics; neurotoxicity; bupivacaine; レボブピバカイン

The aim of this study was to compare the functional and morphologic effects of intrathecally administered R(+), S(-), and racemic bupivacaine using a rat model.Methods : With approval from our Committee on Animal Research, 83 male Sprague-Dawly rats were implanted with 32-gauge intrathecal catheters, and ramdomly divided into four groups to receive a single 2-hr intrathecal infusion (1μl/min) of 1 % R(+) bupivacaine (n = 22), 1 % S(-) bupivacaine (n = 24), 1 % racemic bupivacaine (n = 24), or normal saline (n = 13). Animals were assessed for persistant sensory impairment 4 and 7 days after infusion using the tail-flick test. Tail flick latencies at the proximal, mid, and distal portions of the tail were averaged and converted to % MPE = [(post-drug latency - baseline latency)/(cut-off - baseline latency)] x 100. Animals were sacrificed 7 days after infusion. The nerve roots were sectioned 12 mm caudal to the conus. Each nerve fascicle was assigned an injury score of 0-2 (0 = nomal and mild, 1 = moderate, 2 = sever). The injury score of each cross-section was calculated as the average of all fascicles present in the slide. These data were compared using the Kruskal-Wallis test and Mann-Whitney test.Results : When assessed 4 days after infusion, sensory dysfunction did not appeare in three bupivacaine-treated groups. However, histologic damage remained in three bupivacaine-treated groups ; especially injury by S(-) or racemic bupivacaine was significantly greater than by R(+) bupivacaine.Conclusions : R(+) bupivacaine administered intrathecally has a lower potential for producing neurotoxicity than does S(-) or racemic bupivacaine. We should observe the neurotoxic potential of intrathecally administered levobupivacaine.

The aim of this study was to compare the functional and morphological effects of intrathecal administered R(+), S(-), and racemic bupivacaine using a rat model.Methods: With approval from our Committee on Animal Research, 83 male Sprague-Dawly rats were implanted with 32-gauge intrathecal catheters, and ramdomly divided into four groups to receive a single 2-hr intrathecal infusion （1μl/min）的1％R（+）bupivacaine（n = 22），1％s（ - ）布比丙氨酸（n = 24），1％紫木氨酸（n = 24）或正常盐水（n = 13）。使用尾润测试在输注后4和7天评估动物的持续感觉障碍。将尾部近端，中部和远端部分的尾部弹性延迟进行平均，并转换为％mpe = [（（毒后潜伏期 - 基线潜伏期）/（截止 - 基线潜伏期）] x 100。将神经根切开12毫米的尾部。每个神经束的损伤得分为0-2（0 =名义和轻度，1 =中度，2 = sever）。每个横截面的伤害评分计算为幻灯片中所有束的平均值。使用Kruskal-Wallis检验和Mann-Whitney测试比较这些数据。分析：当输注后4天评估时，在三个布比卡因治疗组中没有出现感觉功能障碍。然而，在三个经过布比卡因治疗的群体中，组织学损害仍然存在。 especially injured by S(-) or racemic bupivacaine was significantly greater than by R(+) bupivacaine.Conclusions: R(+) bupivacaine administered intrathecally has a lower potential for producing neurotoxicity than does S(-) or racemic bupivacaine.We should observe the neurotoxic potential of intrathecally administered levobupivacaine.