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 e ffects at low concentrations. Since lidocaine inhibits endothelium-dep endent vasodilation in vitro, the vasoconstrictor effect of lidocaine may be due to inhibition of endothelium-derived relaxing factor(EDRF/N O). Therefore, the current study was designed to determine the effects of N-G-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide s ynthase, on systemic and pulmonary hemodynamics during lidocaine infus ion. Methods: Systemic and pulmonary hemodynamic effects of lidocaine infusion, 1 mg.kg(-1).min(-1), for 10 min were measured in dogs anesth etized with 1% halothane in oxygen. Dogs were studied twice with an in terval 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 li docaine infusion. The free serum concentration of and protein-binding ratio for lidocaine were measured. Results: With saline pretreatment i n group 1, lidocaine infusion significantly decreased cardiac index (C I) and significantly increased mean pulmonary arterial pressure (MPAP) , pulmonary arterial occlusion pressure (PAOP), systemic vascular resi stance (SVR) and pulmonary vascular resistance (pNR). L-NNA pretreatme nt in group 1 significantly enhanced the changes in CI, MPAP, PAOP, SV R and PVR during lidocaine infusion. In group 2, L-arginine infusion p artially offset the additive effects of L-NNA to the depressive effect s of lidocaine. There were no significant differences in free serum co ncentration 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 i ncluding EDRF/NO pathway is exhausted in halothane-anesthetized dogs.