Profibrillatory effects of verapamil but not of digoxin in the goat model of atrial fibrillation.
BACKGROUND
Verapamil and digoxin have been shown to modulate tachycardia-induced atrial electrical remodeling. The goal of the present study was to determine the direct effects of verapamil and digoxin on atrial fibrillation (AF), before and after electrical remodeling.


RESULTS
In six goats we measured the AF cycle length (AFCL) and duration of AF (DurAF) of 50 consecutive induced paroxysms, before (t = 0) and after 24 hours (t = 24) of electrical remodeling. During AF, conduction velocity (CV(AF)), refractory period (RP(AF)), and type of AF (I, II, III) were determined. Verapamil was administered at a loading dose of 0.1 mg/kg, followed by a continuous (2-hour) infusion of 5 microg/kg/min. Digoxin was given intravenously as a single 0.02 mg/kg bolus. At t = 0 and t = 24, digoxin and verapamil caused a significant slowing of the ventricular rate of >40%. Digoxin had no effect on DurAF, AFCL, CV(AF), or RP(AF). Infusion of verapamil had a direct proarrhythmic effect. Both at t = 0 and t = 24, AFCL and RP(AF) were shortened by about 15%. During acute AF, verapamil prolonged the average duration of AF paroxysms from 7 to 16 seconds. After 24 hours of AF, the proarrhythmic effect was much stronger. Shortly after starting infusion (6 +/- 2 min), verapamil converted paroxysmal AF into sustained AF. As long as verapamil infusion was maintained, AF no longer terminated in any of the goats. This effect was associated with an increase in AF fragmentation from type I to type II-III.


CONCLUSIONS
Verapamil shortens AFCL and RP(AF) in the presence and absence of electrical remodeling. After 24 hours, it exerted a marked proarrhythmic effect and converted paroxysmal (type I) into sustained (type III) AF. In contrast, digoxin had no effect on the rate or stability of AF.
Duytschaever
M F
MF
Department of Physiology, Maastricht University, The Netherlands.
Garratt
C J
CJ
Allessie
M A
MA
D000208:Acute Disease; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D004077:Digoxin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects; D004567:Electrodes, Implanted; D022062:Electrophysiologic Techniques, Cardiac; D006041:Goats; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects*
D000889:Anti-Arrhythmia Agents; D004077:Digoxin; D014700:Verapamil