Inhibitory effects of procainamide on sympathetic nerve activity in humans

Abstract

In experimental animals, procainamide causes hypotension and reductions in efferent vasoconstrictor sympathetic outflow that may result from ganglionic blockade or central nervous system sympathetic inhibition. To test the hypothesis that procainamide decreases sympathetic nerve activity (SNA) in humans, we recorded postganglionic SNA in seven normal subjects in the baseline state and during infusions of procainamide HCl at 50 mg/min (loading) and 8 mg/min (maintenance). At the end of the loading infusion, mean arterial pressure (MAP) had decreased from 88.5 ± 2.4 (mean ± SEM) to 81.5 ± 3.2 mm Hg (p < 0.05), central venous pressure from 6.7 ± 0.7 to 5.4 ± 0.9 mm Hg (p < 0.05), forearm vascular resistance (FVR) from 28 ± 4.8 to 22.3 ± 5.1 resistance units (p < 0.05), and SNA from 259 ± 47 to 94 ± 26 units/min (p < 0.05). These changes persisted during the maintenance infusion. Increased levels of SNA, FVR, and MAP provoked by the cold pressor test were reduced significantly by intravenous procainamide. In eight other subjects, intravenous procainamide HCl (15 mg/kg at 50 mg/min) caused dose-dependent inhibition of SNA that reversed as blood concentrations fell during drug washout. To determine if procainamide causes direct vasodilation, in nine subjects, graded infusions were delivered into the brachial artery at doses that produced no systemic effect. Ipsilateral FVR tended to increase during local intra-arterial infusion of procainamide. These data show that intravenous procainamide causes hypotension, vasodilation, and sympathetic withdrawal. Vasodilation does not result from a direct vasorelaxant effect of the drug. These results suggest that sympathetic inhibition may be a mechanism by which intravenous procainamide causes vasodilation and hypotension in humans.