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ANESTHETIC PHARMACOLOGY

Local Anesthetic Actions on Thromboxane-Induced Platelet Aggregation

Bernard Lo, MD^*, Christian W. Hönemann, MD^*, Rainer Kohrs, MD^*, Markus W. Hollmann, MD^*, Renate K. Polanowska-Grabowska, PhD, Adrian R. L. Gear, PhD, and Marcel E. Durieux, MD PhD^*||

University of Virginia Health System, Departments of *Anesthesiology and Biochemistry & Molecular Genetics, Charlottesville, Virginia; ||Department of Anesthesiology, University Hospital Maastricht, The Netherlands; Department of Anesthesiology, University of Heidelberg, Germany; and Klinik und Poliklinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Münster, Germany

Address correspondence and reprint requests to Christian W. Hönemann, MD, Department of Anesthesiology, Universitätsklinikum Münster, Albert-Schweitzer-Straße 33, 48129 Germany. Address e-mail to honemac{at}uni-muenster.de

Some local anesthetics (LA), in concentrations present in blood during IV or epidural infusion, inhibit thrombus formation in the postoperative period. Studies on thromboxane A₂ (TXA₂) signaling in a recombinant model suggest that interference with TXA₂-induced platelet aggregation may explain, in part, the antithrombotic actions of epidural analgesia and IV LA infusion. In this study we investigated the effects of clinically used LAs (lidocaine, ropivacaine, and bupivacaine) on TXA₂-induced early platelet aggregation (1–5 s) by using quenched-flow and optical aggregometry. Our findings demonstrate that the LAs tested seem to have only a limited ability to inhibit TXA₂-induced platelet aggregation assessed at early times (1–5 s). Therefore, the clinical effects of LAs on thrombi formation are unlikely to be explained by this manner alone. At large LA concentrations, moderate effects were obtained. Prolonged incubation with LA did not significantly increase effectiveness, and the lack of an effect could not be explained by generation of secondary mediators. The results were independent of the anesthetic studied. Local anesthetic effects on TXA₂-induced early platelet aggregation (1–5 s) are unlikely to play a major role in the clinically observed antithrombotic effects of local anesthetics.

IMPLICATIONS: Local anesthetic effects on thromboxane A₂-induced early platelet aggregation (1–5 s) are unlikely to play a major role in the clinically observed antithrombotic effects of local anesthetics. Thus, other potential targets need to be explored.

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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