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ANESTHETIC PHARMACOLOGY

The Effects of S(-)-, R(+)-, and Racemic Bupivacaine on Lysophosphatidate-Induced Priming of Human Neutrophils

Markus W. Hollmann, MD PhD^*,,, Katrin Kurz, MS^*,, Susanne Herroeder, MS^*,, Danja Struemper, MD^,, Klaus Hahnenkamp, MD, Noud S. Berkelmans, MS, Christel G. den Bakker, MS, and Marcel E. Durieux, MD PhD^,

*Department of Anesthesiology, University of Heidelberg, Germany; Department of Anesthesiology, University Hospital Maastricht, The Netherlands; and Department of Anesthesiology, University Hospital Muenster, Germany

Address correspondence and reprint requests to Marcel E. Durieux, MD, PhD, Department of Anesthesiology, University of Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Address e-mail to me.durieux{at}home.nl

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.

This article has been cited by other articles:

				J. G. Bovill Anesthetic Pharmacology: Reflections of a Section Editor Anesth. Analg., November 1, 2007; 105(5): 1186 - 1190. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999