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ANESTHETIC PHARMACOLOGY

Bupivacaine Inhibits Thromboxane A₂-Induced Vasoconstriction in Rat Thoracic Aorta

Klaus Hahnenkamp, MD^*, Joke Nollet, MD, Danja Strümper, MD^*, Tobias Halene^*, Pia Rathman^*, Eike Mortier, MD PhD, Hugo Van Aken, MD PhD^*, Joerg Knapp, MD PhD, Marcel E. Durieux, MD PhD^*, and Christian W. Hoenemann, MD

*Department of Anesthesiology and Intensive Care, University Hospital, Münster, Germany, the Department of Anesthesiology, University Hospital, Gent, Belgium, the Institute of Pharmacology and Toxicology, Westfälische-Wilhelms-Universität, Münster, Germany, and the Department of Anesthesiology, Marienhospital, Vechta, Germany

Address correspondence to Marcel E. Durieux, MD, PhD, Department of Anesthesiology, University of Virginia, PO Box 800710, Charlottesville, VA 22908–0710. Address email to durieux{at}virginia.edu

Plasma levels of thromboxane A₂ (TXA₂), an inflammatory mediator inducing platelet aggregation, bronchoconstriction, and vasoconstriction, are increased in the perioperative period. A major role in the pathogenesis of perioperative thromboembolic and ischemic syndromes is attributed to this prostanoid. Local anesthetics (LA) inhibit signaling of TXA₂ receptors expressed in cell models. Therefore, we hypothesized that LA may inhibit vasoconstriction induced by the TXA₂ analog U46619 in rat thoracic aorta. Rings (3-mm length) of the rat thoracic aorta were mounted in organ baths and isometric contractile force was measured. Rings, with or without endothelium, were incubated for 60 min in bupivacaine (10^–6 or 10^–5 M) or Krebs-Henseleit solution (control group) and subsequently exposed to cumulative concentrations of U46619 (10^–10 to 10^–6 M). The reversibility of the TXA₂-induced vasoconstriction by bupivacaine was also studied. Pretreatment of rings with bupivacaine concentration-dependently diminished TXA₂-induced contraction in rat aortic rings. We found no significant differences in relaxing effect of bupivacaine between rings with and without endothelium. Contraction in rings established with U46619 could not be reversed by cumulative concentrations of bupivacaine. Bupivacaine inhibited carbachol-induced vascular relaxation. This study provides experimental evidence that bupivacaine is an endothelium-independent inhibitor of TXA₂-induced vasoconstriction of rat thoracic aorta.

IMPLICATIONS: Bupivacaine inhibits thromboxane A₂-induced vasoconstriction in rat thoracic aorta rings in an endothelium-independent manner.

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