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Ropivacaine Attenuates Pulmonary Vasoconstriction Induced by Thromboxane A2 Analogue in the Isolated Perfused Rat Lung
  1. Lars G. Fischer, M.D.,
  2. Christian W. Hönemann, M.D.,
  3. James T. Patrie, M.S.,
  4. Marcel E. Durieux, M.D., Ph.D. and
  5. George F. Rich, M.D., Ph.D.
  1. From the Department of Anesthesiology, University of Virginia Health Center (L.G.F., C.W.H., M.E.D., G.F.R.), the Division of Biostatistics and Epidemiology, the University of Virginia (J.T.P.), Charlottesville, Virginia; and Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Westfälische-Wilhelms-Universität Münster (L.G.F., C.W.H.), Münster, Germany
  1. Correspondence: George F. Rich, M.D., Ph.D., the Department of Anesthesiology, the University of Virginia Health System, PO Box 10010, Charlottesville, VA 22906-0010. E-mail: gfr2f{at}virginia.edu

Abstract

Background and Objectives Thromboxane A2 (TXA2) activation is involved in several pathophysiological states in producing pulmonary hypertension. Local anesthetics (LA) inhibit signaling of TXA2 receptors expressed in cell models. Therefore, we hypothesized that LA may inhibit pulmonary vasoconstriction induced by the TXA2 analogue U 46619 in an isolated lung model.

Methods Isolated rat lungs were perfused with physiological saline solution and autologous blood with or without the LA lidocaine, bupivacaine, ropivacaine, or the permanently charged lidocaine analogue QX 314 (all 1 μg/mL) as a pretreatment. Subsequently, pulmonary vasoconstriction was induced by 3 concentrations of U 46619 (25, 50, and 100 ng/mL) and the change in pulmonary artery pressure (Pa) was compared with each LA. In a second experiment, Pa responses to angiotensin II (0.1 μg), hypoxic pulmonary vasoconstriction (HPV, 3% O2 for 10 minutes), or phenylephrine (0.1 μg) were assessed to determine the specificity of ropivacaine effects on TXA2 receptors. Finally, reversibility of pulmonary vasoconstriction was determined by adding ropivacaine to the perfusate after pulmonary vasoconstriction was established with U 46619.

Results Ropivacaine, but not bupivacaine, lidocaine, or QX 314 significantly attenuated pulmonary vasoconstriction induced by 50 ng/mL U 46619 (35.9%, P < .003) or 100 ng/mL U 46619 (45.2%, P < .001). This effect of ropivacaine was likely to be specific for the thromboxane receptor because pulmonary vasoconstriction induced by angiotensin II, HPV, or phenylephrine was not altered. Ropivacaine did not reverse vasoconstriction when it was administered after U 46619.

Conclusions Ropivacaine, but not lidocaine, bupivacaine, or QX 314 at 1 μg/mL, attenuates U 46619-induced pulmonary vasoconstriction in an isolated perfused rat lung model. These results support evidence that the clinically used enantiomer S(-)-ropivacaine may inhibit TXA2 signaling.

  • Thromboxane signaling
  • Pulmonary circulation
  • Local anesthetic

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Footnotes

  • Presented in part at the Annual Mmeeting of the American Society of Anesthesiologists, Orlando, Florida, October 1998.

    Dr. Fischer is supported by Innovative Medizinische Forschung Münster, Germany (FI-6-2-98-01).

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