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

Abstract

Background: 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.

Objective: The purpose of this study was to test the hypothesis that the efficacy and time course of AF cardioversion by sodium channel current (I_Na) block can be improved by mild elevation of extracellular potassium ([K⁺]₀).

Methods: 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.

Results: At [K⁺]₀ of 4 mM (baseline), persistent AF (>1 hour) was induced in 5 of 5 atria in the presence of 0.5 μM ACh. Flecainide alone (1.5 μM) cardioverted 3 of 6 atria at 4 mM [K⁺]₀, 1 of 6 atria at 3 mM [K⁺]₀, 5 of 5 atria at 5 mM and 6 mM [K⁺]₀, and 4 of 4 atria at 8 mM [K⁺]₀. In the absence of flecainide, an increase in [K⁺]₀ from 4 mM to 5, 6, and 8 mM terminated AF in 0 of 5, 2 of 6, and 4 of 4 atria, respectively. The time to conversion was also abbreviated by elevation of [K⁺]₀. After AF termination with flecainide plus elevated [K⁺]₀, AF was either not inducible or brief (<100 seconds). Combined flecainide and elevated [K⁺]₀ (6 mM) caused an atrial preferential depression of excitability.

Conclusion: Our findings suggest that a combination of I_Na 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.

Keywords: Atrial fibrillation; Cardioversion; Flecainide; Hyperkalemia; Hypokalemia; Pharmacology.