Introduction: Local anesthetics (LAs) are frequently used during anesthesia; however, they may influence granulocyte function which in turn could modify immune responses in the perioperative period. Therefore, the aim of this study was to investigate the impact of clinically used doses of bupivacaine and lidocaine on granulocyte function with regard to migration, reactive oxygen species (ROS) production, neutrophil extracellular traps (NETosis) formation, and viability.
Methods: A total of 38 granulocyte-enriched samples from healthy subjects were obtained by whole blood lysis. Polymorphonuclear neutrophil (PMN) samples were incubated simultaneously with different concentrations of either bupivacaine (0.03– 3.16 mmol/L) or lidocaine (0.007– 14.21 mmol/L), or without drug (control). Live cell imaging was conducted in order to observe granulocyte chemotaxis, migration, ROS production, and NETosis. Flow cytometry was used to analyze viability and antigen expression.
Results: The track length (TL) of PMNs exposed to bupivacaine concentrations of 0.16 mmol/L and above significantly decreased compared to the control. Low concentrations of lidocaine were associated with slight but significant increases in TL, whereas this changed with concentrations above 1.4 mmol/L, showing a significant decrease in TL. PMN incubated with bupivacaine concentrations of 1.58 mmol/L and above or lidocaine concentrations of at least 3.6 mmol/L showed no migration or chemotaxis at all. Time to onset of maximal ROS production and time for half-maximal NETosis decreased in a dose-dependent manner for both substances. Equipotency in NETosis induction was reached by bupivacaine (1.1 mmol/L) at significantly lower concentrations than lidocaine (7.96 mmol/L). Cell viability and oxidative burst were unaffected by LAs.
Conclusion: Local anesthetics in clinically used doses ameliorate granulocyte defense mechanisms, thus indicating their potentially decisive effect during the perioperative period.

Keywords: local anesthetics, granulocytes, immune modulation, surgical trauma, inflammation


中文翻译：

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局部麻醉剂诱导粒细胞阻滞和改变免疫功能对围手术期结果的潜在影响

简介：麻醉期间经常使用局部麻醉剂（LAs）；然而，它们可能会影响粒细胞功能，进而改变围手术期的免疫反应。因此，本研究的目的是调查临床使用剂量的布比卡因和利多卡因对粒细胞在迁移、活性氧 (ROS) 产生、中性粒细胞胞外陷阱 (NETosis) 形成和活力方面的功能的影响。
方法：通过全血裂解获得了来自健康受试者的总共 38 个富含粒细胞的样本。多形核中性粒细胞 (PMN) 样品与不同浓度的布比卡因 (0.03–3.16 mmol/L) 或利多卡因 (0.007–14.21 mmol/L) 或不使用药物（对照）同时孵育。进行活细胞成像以观察粒细胞趋化性、迁移、ROS产生和NETosis。流式细胞术用于分析活力和抗原表达。
结果：与对照组相比，暴露于 0.16 mmol/L 及以上浓度的布比卡因的 PMN 的轨迹长度 (TL) 显着降低。低浓度的利多卡因与 TL 的轻微但显着增加有关，而当浓度高于 1.4 mmol/L 时，这种情况发生变化，显示 TL 显着降低。与浓度为 1.58 mmol/L 及以上的布比卡因或浓度至少为 3.6 mmol/L 的利多卡因孵育的 PMN 完全没有迁移或趋化性。对于这两种物质，最大 ROS 产生的开始时间和半最大 NETosis 的时间以剂量依赖性方式减少。布比卡因 (1.1 mmol/L) 在显着低于利多卡因 (7.96 mmol/L) 的浓度下达到了 NETosis 诱导的等效性。细胞活力和氧化爆发不受 LA 的影响。
结论：临床使用剂量的局麻药可改善粒细胞防御机制，从而表明其在围手术期具有潜在的决定性作用。

关键词：局部麻醉剂，粒细胞，免疫调节，手术创伤，炎症