Lidocaine attenuates efferent sympathetic responses to stress in humans

Abstract

The effects of antiarrhythmic doses of lidocaine on efferent sympathetic outflow or sympathetic responses to autonomic stimuli in humans are unknown. In the present study, direct recordings of postganglionic muscle sympathetic nerve activity (MSNA), which modulates vascular tone, were obtained from the peroneal nerve of 22 healthy volunteers (aged 20 to 27 years). Baseline cardiac intervals (ECG), arterial pressure (radial artery), central venous pressure (CVP, jugular vein), forearm vascular resistance (FVR, Hg-in-Silastic plethysmography), and MSNA were identical in two randomized study groups (lidocaine [L], 1.5 mg/kg bolus, followed by 2 mg/ min infusion, n = 12; and placebo [P] saline bolus and infusion, n = 10). Each underwent a cold pressor test (CPT, ice packs to foot for 90 seconds) and baroreceptor test (sequential boluses of 100 μg of sodium nitroprusside and 100 μg of phenylephrine). Five minutes after the bolus administration of L, plasma L levels were 3 μg/mL, which was associated with significant ( P < 0.05) increases in systolic and diastolic pressures (6.6 ± 2.4 and 5.5 ± 1.1 mm Hg). This elicited significant reflex decreases in MSNA (-3 ± 1.1 bursts/100 cardiac cycles) and RR interval (-63 ± 14 ms). The hypertension, tachycardia, forearm vasoconstriction, and MSNA increase in response to the CPT were significantly attenuated and the sympathoexcitatory response to baroreceptor unloading was blunted by L. These responses were not altered during the administration of P. In the steady-state L infusion period, plasma levels were subtherapeutic (1 μg/mL) and were insufficient to consistently alter autonomic stress responses. Thus, therapeutic plasma levels of L produce small increases in blood pressure and reflex decreases in the cardiac interval and MSNA. Moreover, these concentrations of L attenuate the sympathetic responses to autonomic stress in humans.