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


CONCLUSIONS
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.
D000465:Algorithms; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008246:Lysophospholipids / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects*; D009865:Oocytes; D016877:Oxidants / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism; D014981:Xenopus
D000779:Anesthetics, Local; D003574:Cytochrome c Group; D008246:Lysophospholipids; D016877:Oxidants; D013481:Superoxides; D002045:Bupivacaine