Mild elevation of extracellular potassium greatly potentiates the effect of sodium channel block to cardiovert atrial fibrillation: The Lankenau approach

Abstract

Cardioversion of atrial fibrillation (AF) is a common clinical necessity and there is a need for more effective and safe options for acute cardioversion of AF. To test the hypothesis that the efficacy and time course of AF cardioversion by sodium channel current (INa) block can be improved by mild elevation of extracellular potassium ([K+]0). Using a canine acetylcholine (ACh)-mediated AF model (isolated coronary-perfused right atrial preparations with a rim of right ventricle), we evaluated the ability of flecainide to suppress AF in the presence of [K+]0 ranging from 3 to 8 mM. At [K+]0 of 4 mM (baseline), persistent AF (>1 hour) was induced in 5/5 atria in the presence of 0.5 μM ACh. Flecainide alone (1.5 μM) cardioverted 3/6 atria at 4 mM [K+]0, 1/6 atria at 3 mM [K+]0, 5/5 atria at 5 mM and 6 mM [K+]0, and 4/4 atria at 8 mM [K+]0. In the absence of flecainide, an increase in [K+]0 from 4 to 5, 6 and 8 mM terminated AF in 0/5, 2/6, and 4/4 atria. The time to conversion was also abbreviated by elevation of [K+]0. Following AF termination with flecainide plus elevated [K+]0, AF was either not inducible or brief (< 100 sec). Combined flecainide and elevated [K+]0 (6 mM) caused an atrial preferential depression of excitability. Our findings suggest that a combination of INa block accompanied by mild elevation of serum potassium may be a novel approach to more effectively, rapidly, and safely cardiovert AF and prevent its recurrence in the short term.