Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome

Kolle, Gesche and Metterlein, Thomas and Gruber, Michael and Seyfried, Timo and Petermichl, Walter and Pfaehler, Sophie-Marie and Bitzinger, Diane and Wittmann, Sigrid and Bredthauer, Andre (2021) Potential Impact of Local Anesthetics Inducing Granulocyte Arrest and Altering Immune Functions on Perioperative Outcome. JOURNAL OF INFLAMMATION RESEARCH, 14. pp. 1-12. ISSN , 1178-7031

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: CD11B EXPRESSION; OXIDATIVE BURST; BUPIVACAINE; LIDOCAINE; ROPIVACAINE; NEUTROPHILS; CYTOTOXICITY; PHAGOCYTOSIS; MODULATION; MIGRATION; local anesthetics; granulocytes; immune modulation; surgical trauma; inflammation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Anästhesiologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 05 Sep 2022 06:04
Last Modified: 05 Sep 2022 06:04
URI: https://pred.uni-regensburg.de/id/eprint/46517

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