Lidocaine-induced hemodynamic effects are enhanced by the inhibition of endothelium-derived relaxing factor in dogs

Background: Lidocaine has been shown to have direct vasoconstrictive effects at low concentrations. Since lidocaine inhibits endothelium-dependent vasodilation in vitro, the vasoconstrictor effect of lidocaine may be due to inhibition of endothelium-derived relaxing factor(EDRF/NO). Therefore, the current study was designed to determine the effects of N-G-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide synthase, on systemic and pulmonary hemodynamics during lidocaine infusion. Methods: Systemic and pulmonary hemodynamic effects of lidocaine infusion, 1 mg.kg(-1).min(-1), for 10 min were measured in dogs anesthetized with 1% halothane in oxygen. Dogs were studied twice with an interval of 1 week in a cross-over study and were assigned to one of two groups that received saline or L-NNA intravenously in group 1 (n=8), or L-MNA or L-NNA+L-arginine which reverses the nitric oxide synthesis inhibitor effect of L-NNA, intravenously in group 2 (n=8) prior to lidocaine infusion. The free serum concentration of and protein-binding ratio for lidocaine were measured. Results: With saline pretreatment in group 1, lidocaine infusion significantly decreased cardiac index (CI) and significantly increased mean pulmonary arterial pressure (MPAP), pulmonary arterial occlusion pressure (PAOP), systemic vascular resistance (SVR) and pulmonary vascular resistance (pNR). L-NNA pretreatment in group 1 significantly enhanced the changes in CI, MPAP, PAOP, SVR and PVR during lidocaine infusion. In group 2, L-arginine infusion partially offset the additive effects of L-NNA to the depressive effects of lidocaine. There were no significant differences in free serum concentration of or protein-binding ratio far lidocaine among the groups. Conclusion: In contrast to in vitro study, vasoconstrictor effect of lidocaine is enhanced when a capacity for compensatory vasodilation including EDRF/NO pathway is exhausted in halothane-anesthetized dogs.