INHIBITORY EFFECT OF LOCAL-ANESTHETICS ON REACTIVE OXYGEN SPECIES PRODUCTION BY HUMAN NEUTROPHILS

Background: Reactive oxygen species (ROS) generated from neutrophils a ccumulated in various major organs are thought to play a pivotal role in the pathogenesis of host auto-injury. Lidocaine has been shown to r educe the injury. We investigated the effect of local anaesthetics (li docaine, mepivacaine and bupivacaine) on ROS production by neutrophils using an in vitro system. Methods: We measured the production of supe roxide (ferric ytochrome c method), hydrogen peroxide (H2O2: scopoleti n fluorescence technique), and hydroxyl radical (OH .: ethylene gas me thod) by neutrophils isolated from human adult volunteers in the absen ce and presence of lidocaine (2-200 mu g/mL), mepivacaine (3-300 mu g/ mL), and bupivacaine (3-300 mu g/mL). We also measured the ROS generat ion in a cell-free (xanthine-xanthine oxidase) system. Results: Lidoca ine and mepivacaine at higher levels significantly decreased the produ ction of ROS by neutrophils. However, these local anaesthetics at clin ically relevant blood concentrations had no effect on the levels of RO S. Furthermore, lidocaine and mepivacaine failed to reduce ROS generat ed by the cell-free system. Bupivacaine did not decrease ROS generatio n by either generating system. Conclusion: In conclusion, in the prese nt in vitro system, only concentrations of lidocaine and mepivacaine 1 00-fold higher than clinically feasible ones reduced ROS production by human neutrophils. However, the local anaesthetics at clinically rele vant blood concentrations had no suppressive effect. Further studies u sing in vivo systems are required to elucidate the inhibitory effects of local anaesthetics on ROS generation in clinical settings. (C) Acta Anaesthesiologica Scandinavica 41 (1997).