Mikawa K, Akamatsu H, Nishina K, Shiga M, Maekawa N, Obara H, Niwa Y
Department of Anaesthesiology, Kobe University School of Medicine, Japan.
Acta Anaesthesiol Scand. 1997 Apr;41(4):524-8. doi: 10.1111/j.1399-6576.1997.tb04735.x.
Reactive oxygen species (ROS) generated from neutrophils accumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto-injury. Lidocaine has been shown to reduce the injury. We investigated the effect of local anaesthetics (lidocaine, mepivacaine and bupivacaine) on ROS production by neutrophils using an in vitro system.
We measured the production of superoxide (ferricytochrome c method), hydrogen peroxide (H2O2: scopoletin fluorescence technique), and hydroxyl radical (OH.: ethylene gas method) by neutrophils isolated from human adult volunteers in the absence and presence of lidocaine (2-200 micrograms/mL), mepivacaine (3-300 micrograms/mL), and bupivacaine (3-300 micrograms/mL). We also measured the ROS generation in a cell-free (xanthine-xanthine oxidase) system.
Lidocaine and mepivacaine at higher levels significantly decreased the production of ROS by neutrophils. However, these local anaesthetics at clinically relevant blood concentrations had no effect on the levels of ROS. Furthermore, lidocaine and mepivacaine failed to reduce ROS generated by the cell-free system. Bupivacaine did not decrease ROS generation by either generating system.
In conclusion, in the present in vitro system, only concentrations of lidocaine and mepivacaine 100-fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically relevant blood concentrations had no suppressive effect. Further studies using in vivo systems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings.
积聚在各个主要器官中的中性粒细胞产生的活性氧（ROS）被认为在宿主自身损伤的发病机制中起关键作用。利多卡因已被证明可减轻损伤。我们使用体外系统研究了局部麻醉药（利多卡因、甲哌卡因和布比卡因）对中性粒细胞产生ROS的影响。
我们测量了在不存在和存在利多卡因（2 - 200微克/毫升）、甲哌卡因（3 - 300微克/毫升）和布比卡因（3 - 300微克/毫升）的情况下，从成年人类志愿者分离的中性粒细胞产生超氧化物（铁细胞色素c法）、过氧化氢（H2O2： scopoletin荧光技术）和羟基自由基（OH·：乙烯气体法）的情况。我们还在无细胞（黄嘌呤 - 黄嘌呤氧化酶）系统中测量了ROS的产生。
较高浓度的利多卡因和甲哌卡因显著降低了中性粒细胞产生ROS的量。然而，这些局部麻醉药在临床相关血药浓度下对ROS水平没有影响。此外，利多卡因和甲哌卡因未能减少无细胞系统产生的ROS。布比卡因对两种产生系统产生的ROS均无降低作用。
总之，在目前的体外系统中，只有浓度比利多卡因和甲哌卡因的临床可行浓度高100倍时，才会减少人中性粒细胞产生ROS。然而，临床相关血药浓度的局部麻醉药没有抑制作用。需要使用体内系统进行进一步研究，以阐明局部麻醉药在临床环境中对ROS产生的抑制作用。
