Chloroquine Terminates Stretch-Induced Atrial Fibrillation More Effectively Than Flecainide in the Sheep Heart

Abstract

Blockade of inward-rectifier K ⁺ channels by chloroquine terminates reentry in cholinergic atrial fibrillation (AF). However, it is unknown whether inward-rectifier K ⁺ channels and reentry are also important in maintaining stretch-induced AF (SAF). We surmised that reentry underlies SAF, and that abolishing reentry with chloroquine terminates SAF more effectively than traditional Na ⁺ -channel blockade by flecainide. Thirty Langendorff-perfused sheep hearts were exposed to acute and continuous atrial stretch, and mapped optically and electrically. AF dynamics were studied under control and during perfusion of either chloroquine (4 µmol/L, n=7) or flecainide (2–4 µmol/L, n=5). Chloroquine increased rotor core size and decreased reentry frequency from 10.6 ± 0.7 Hz in control to 6.3 ± 0.7 Hz ( P 8 Hz. During pacing (n=11), flecainide reversibly reduced conduction velocity (≈30% at cycle length 300, 250, and 200 ms; P P P + channel blockade profile and suggest that reentry is important to maintain acute SAF.