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 (P_a) was compared with each LA. In a second experiment, P_a 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.