Dataset Information
Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart.
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ABSTRACT: Background
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.Methods and results
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<0.005) just before restoring sinus rhythm (7/7). Flecainide had lesser effects on core size and reentry frequency than chloroquine and did not restore sinus rhythm (0/5). Specific IKr blockade by E-4031 (n=7) did not terminate AF when frequency values were >8 Hz. During pacing (n=11), flecainide reversibly reduced conduction velocity (≈30% at cycle length 300, 250, and 200 ms; P<0.05) to a larger extent than chloroquine (11% to 19%; cycle length, 300, 250, and 200 ms; P<0.05). Significant action potential duration prolongation was demonstrable only for chloroquine at cycle length 300 (12%) and cycle length 250 ms (9%) (P<0.05).Conclusions
Chloroquine is more effective than flecainide in terminating SAF in isolated sheep hearts by significantly increasing core size and decreasing reentry frequency. Chloroquine's effectiveness may be explained by its inward-rectifier K+ channel blockade profile and suggest that reentry is important to maintain acute SAF.
SUBMITTER: Filgueiras-Rama D
PROVIDER: S-EPMC3380168 | biostudies-literature | 2012 Jun
REPOSITORIES: biostudies-literature
Publications
Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart.
Circulation. Arrhythmia and electrophysiology 20120330 3
<h4>Background</h4>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.<h4>Methods and results</h4>Thirty Langendorff-perfused sheep he ...[more]
