The effects of S(-)-, R(+)-, and racemic bupivacaine on lysophosphatidate-induced priming of human neutrophils

Anesth Analg. 2003 Oct;97(4):1053-1058. doi: 10.1213/01.ANE.0000080157.07960.93.

Abstract

Local anesthetics modulate inflammatory responses and may therefore be potentially useful in mitigating perioperative inflammatory injury. The inflammatory modulating effects of S(-)-bupivacaine are not known. Therefore, we compared the effects of S(-)-bupivacaine, R(+)-bupivacaine, and racemic bupivacaine on neutrophil function and receptor signaling. Priming (by lysophosphatidic acid [LPA]) and activation (by N-formylmethionine-leucyl-phenylalanine) of superoxide release by isolated human neutrophils was studied by using a cytochrome c-reduction assay. LPA receptor signaling in Xenopus oocytes was studied by using voltage clamp. All three local anesthetics were without effect on activation. S(-)-Bupivacaine inhibited priming more than did racemic bupivacaine; R(+)-bupivacaine was without effect. At 10(-4) M, S(-)-bupivacaine inhibited approximately 50%. Comparable results were obtained in our recombinant model, where S(-)-bupivacaine most effectively inhibited LPA signaling. Compared with racemic bupivacaine and other anesthetics, S(-)-bupivacaine appears particularly effective in suppressing neutrophil priming, a process responsible in part for the overactive neutrophil response.

Implications: Overactive inflammatory responses underlie several perioperative disorders. Compared with racemic bupivacaine and other anesthetics, S(-)-bupivacaine appears particularly effective in suppressing neutrophil priming, a process responsible in part for the overactive neutrophil response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms
  • Anesthetics, Local / pharmacology*
  • Animals
  • Bupivacaine / pharmacology*
  • Cytochrome c Group / metabolism
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Lysophospholipids / pharmacology*
  • Neutrophils / drug effects*
  • Oocytes
  • Oxidants / metabolism
  • Signal Transduction / drug effects
  • Stereoisomerism
  • Superoxides / metabolism
  • Xenopus

Substances

  • Anesthetics, Local
  • Cytochrome c Group
  • Lysophospholipids
  • Oxidants
  • Superoxides
  • Bupivacaine