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

本研究的目的是使用大鼠模型比较鞘内注射R（+）、S（-）和外消旋布比卡因对功能和形态的影响。在我们的动物研究委员会的批准下，83只雄性Sprague-Dawly大鼠被植入32号鞘内导管，随机分为4组，分别以1 μ l/min的速度鞘内注入1%R（+）布比卡因（n = 22），1%S（-）布比卡因（n = 24），1%外消旋布比卡因（n = 24）或生理盐水（n = 13）。在输注后4天和7天，使用甩尾试验评估动物的持续感觉障碍。对尾部近端、中部和远端的甩尾潜伏期取平均值，并转换为%MPE =[（给药后潜伏期-基线潜伏期）/（截止值-基线潜伏期）] x 100。输注后7天处死动物。将神经根在圆锥尾部12 mm处切片。每个神经束的损伤评分为0 - 2（0 =正常和轻度，1 =中度，2 =重度）。每个横截面的损伤评分计算为载玻片中存在的所有神经束的平均值。这些数据进行了比较，使用Kruskal-Wallis检验和Mann-Whitney test.Results：当评估4天后输液，感觉功能障碍并没有出现在三个布比卡因治疗组。然而，组织学损伤仍然在三个布比卡因治疗组，特别是损伤S（-）或外消旋布比卡因是显着大于R（+）bupivacaine. Conclusions：R（+）布比卡因鞘内给药产生神经毒性的可能性较低比S（-）或外消旋布比卡因。我们应该观察鞘内注射左旋布比卡因的神经毒性潜力。

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.