Electrophysiological effects of flecainide and sotalol in the human atrium during persistent atrial fibrillation.
OBJECTIVE
Atrial fibrillation (AF) shortens the atrial action potential and the atrial refractory period. These changes promote persistence of AF. Pharmacological prolongation of atrial action potential duration (APD) may therefore help to prevent recurrent AF. In addition to prolonging APD, sodium channel blockers may prevent AF by inducing post-repolarization refractoriness (PRR). We studied whether two antiarrhythmic drugs (sotalol, flecainide) prolong APD or induce PRR in the fibrillating human atrium.


METHODS
In 12 patients with persistent AF (11 male, 58 +/- 5 yrs, 27 +/- 7 months duration of AF), we recorded monophasic action potentials from the right atrial appendage and inferior right atrium at baseline and 15 minutes after intravenous administration of sotalol (1.5 mg/kg) or flecainide (2 mg/kg). APD and effective refractory periods (ERP) were determined.


RESULTS
Both drugs prolonged APD90 during AF (flecainide from 109 +/- 7 ms to 137 +/- 10 ms, sotalol from 108 +/- 6 ms to 131 +/- 8 ms, both p < 0.05 vs. baseline). Sotalol prolonged ERP in parallel to APD (from 119 +/- 8 ms to 139 +/- 8 ms, p < 0.05). Flecainide induced PRR by prolonging ERP more than APD90 (from 134 +/- 9 ms to 197 +/- 28 ms, p < 0.05 vs. baseline and vs. sotalol).


CONCLUSIONS
Flecainide and sotalol prolong the atrial action potential during atrial fibrillation in humans. In addition, flecainide induces atrial PRR. These electrophysiological effects may reduce AF recurrences and prevent their persistence.
Kirchhof
Paulus
P
Medizinische Klinik und Poliklinik C Kardiologie und Angiologie, Universitätsklinikum Münster, Münster, Germany. kirchhp@uni-muenster.de
Engelen
Markus
M
Franz
Michael R
MR
Ribbing
Michael
M
Wasmer
Kristina
K
Breithardt
Günter
G
Haverkamp
Wilhelm
W
Eckardt
Lars
L
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020517:Atrial Appendage / Q000187:drug effects* / Q000503:physiopathology; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D004554:Electric Countershock; D005260:Female; D005424:Flecainide / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D055502:Secondary Prevention; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D013015:Sotalol / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D013015:Sotalol; D005424:Flecainide