d,l-Sotalol reverses abbreviated atrial refractoriness and prevents promotion of atrial fibrillation in a canine model with left ventricular dysfunction induced by atrial tachypacing.
BACKGROUND
This study evaluated antiarrhythmic effects of d,l-sotalol in a canine atrial fibrillation (AF) model with left ventricular dysfunction.


RESULTS
Thirteen beagles (Sotalol group n=7 and Control group n=6) were subjected to atrial tachypacing (ATP) (400 beats/min) with intact atrioventricular conduction for 4 weeks. Oral d,l-sotalol (2 mg/kg) was administered 1 week after starting ATP and continued throughout the experiment. One week after starting ATP, atrial effective refractory periods (AERPs) were shortened in both groups. However, d,l-sotalol treatment gradually prolonged AERP, resulting in a significant prolongation of AERP compared with the Control group at 4 weeks (Control 76 +/-4 and Sotalol 126 +/-5 ms, p<0.01). d,l-Sotalol treatment showed lower AF inducibility and shorter AF duration at 4 weeks. In the control group, expressions of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA were downregulated by 46.2% and 43.0%, respectively, after 4 weeks of ATP; d,l-sotalol treatment did not affect these changes.


CONCLUSIONS
d,l-Sotalol treatment prolonged AERP, even after atrial electrical remodeling had developed, and prevented AF perpetuation without affecting downregulated expression of L-type Ca(2+) channel alpha1c and Kv4.3 mRNA in an ATP-induced canine AF model.
Sakamoto
Tamotsu
T
Second Department of Internal Medicine, University of Toyama, Japan.
Fujiki
Akira
A
Nakatani
Yosuke
Y
Sakabe
Masao
M
Mizumaki
Koichi
K
Hashimoto
Norio
N
Inoue
Hiroshi
H
D000200:Action Potentials; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016275:Atrial Function / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000235:genetics; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation; D004452:Echocardiography; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005355:Fibrosis; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051672:Shal Potassium Channels / Q000235:genetics; D013015:Sotalol / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; C419385:L-type calcium channel alpha(1C); D012333:RNA, Messenger; D051672:Shal Potassium Channels; D013015:Sotalol