Abstract 10988: Chloroquine Effectively Terminates Acute Stretch-Induced Atrial Fibrillation (AF) in the Isolated Sheep Heart.
Introduction: Antiarrhythmic drugs have been disappointing in the treatment of AF. The antimalarial agent chloroquine inhibits inward rectifying potassium channels (IK1, IKATP and IKACh) and terminates fibrillation in the atria and ventricles at therapeutic doses. We surmised that, by targeting high frequency AF drivers, chloroquine terminates stretch-induced AF more effectively than flecainide.
Methods: Hearts excised from 12 sheep were Langendorff-perfused. After atrial trans-septal puncture the intra-atrial pressure was increased to 14 cm H2O to induce continuous atrial stretch. Simultaneous optical and electrogram recordings were obtained from the atria and pulmonary veins, respectively. Control action potential duration (APD) and conduction times were measured at cycle lengths 300–250–200 ms before inducing AF by rapid pacing, and after AF terminated spontaneously, or by DC shock, in the presence of chloroquine (4 μM/L) or flecainide (2–4 μM/L).
Results: Chloroquine tended to increase APD, but the effect was not significant. APD was shorter on flecainide (p<0.05). Conduction time increased in both groups (p<0.05). After induction, AF was allowed to continue for 15 min of control. In all 7 hearts, chloroquine reduced AF frequency and restored normal sinus rhythm (NSR) after 4–19 min (Figure). Flecainide reduced the AF frequency from 11±2.8 Hz after 50 min but did not restore NSR (n=5), even at 4 μM/L during the last 30 min (p=0.0013; Fisher′s exact test). It was not possible to re-induce sustained AF in the presence of chloroquine (n=7). Conversely, upon cardioversion, AF was re-induced and sustained with flecainide (n=4). AF was re-induced and sustained in both groups after washout.
Conclusions: chloroquine is highly effective in terminating stretch-induced AF in sheep hearts. Its effects may be the result of inward rectifier channel blockade, or perhaps blockade of stretch activated channels. The results may lead to novel therapeutic strategies.
- © 2010 by American Heart Association, Inc.