Effects of lidocaine and bupivacaine on isolated rabbit mesenteric capacitance veins

Background and Objectives. The direct effects of circulating lidocaine and bupivacaine on splanchnic capacitance veins have not been examined previously. This article reports on the effects of clinically relevant concentrations of lidocaine and bupivacaine on adrenergic responsiveness of isolated rabbit mesenteric veins and examines the mechanism of changes. Methods. Rings of ileal mesenteric capacitance veins were suspended in tissue baths for isometric tension measurements. Effects of lidocaine and bupivacaine on contractile responses to adrenergic nerve stimulation, exogenous norepinephrine (10(-6) M NE), and potassium chloride (80 mM KCl) were examined in endothelium-intact, L-NAME (10(-4) M) treated or denuded veins. Results. Constriction in response to adrenergic nerve stimulation was attenuated by lidocaine and bupivacaine in a dose-dependent manner, with the potency of bupivacaine being higher than lidocaine. Unstimulated or potassium-constricted veins with and without endothelium were unaffected by lidocaine (0.25-100 mu g/mL) and bupivacaine (0.1-100 mu g/mL). In veins preconstricted by exogenously administered NE, a cumulative increase of both anesthetics produced no effect at low doses, an augmentation of constriction to NE at 5-20 mu g/mL bupivacaine and 20-100 mu g/mL lidocaine, and minimal effect at 50-100 mu g/mL bupivacaine. These actions persisted in denuded or L-NAME treated veins. Nonincremental delivery of high concentrations of lidocaine or bupivacaine produced relaxation of NE and potassium-constricted rings in the absence and presence of L-NAME. Conclusions. Lidocaine and bupivacaine in concentrations typical during uncomplicated regional anesthesia inhibit adrenergic neurotransmission in rabbit mesenteric capacitance veins and produce modest venodilatation. Higher doses, resembling concentrations during accidental intravascular injection, result in substantial loss in vasomotor control of these capacitance vessels, which may contribute to hemodynamic effects.