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.

本研究的目的是使用大鼠模型比较鞘内注射 R(+)、S(-) 和种族布比卡因的功能和形态学影响。 方法：经我们动物研究委员会批准，83 只雄性 Sprague-Dawly大鼠被植入 32 号鞘内导管，随机分为 4 组，接受单次 2 小时鞘内输注（1μl/min） 1% R(+) 布比卡因 (n = 22)、1% S(-) 布比卡因 (n = 24)、1% 种族布比卡因 (n = 24) 或生理盐水 (n = 13) 对动物进行持续性评估。输注后 4 天和 7 天使用甩尾测试检测近端、中部和远端部分的甩尾潜伏期。对尾部进行平均并转换为% MPE = [(药物后潜伏期-基线潜伏期)/(截止-基线潜伏期)] x 100。输注后7天处死动物。将神经根从尾部切开12毫米。每个神经束的损伤评分为 0-2（0 = 正常和轻度，1 = 中度，2 = 严重）。每个横截面的损伤评分计算为平均值。使用 Kruskal-Wallis 检验和 Mann-Whitney 检验对载玻片中存在的所有束进行比较。结果：输注后 4 天进行评估时，三个布比卡因治疗组没有出现感觉功能障碍，但组织学损伤仍然存在。在三个布比卡因治疗组中；特别是 S(-) 或外消旋布比卡因的损伤明显大于 R(+) 布比卡因。结论：R(+)鞘内给药的布比卡因产生神经毒性的可能性低于S(-)或外消旋布比卡因，我们应该观察鞘内给药的左布比卡因的神经毒性可能性。