Verapamil prolongs atrial fibrillation by evoking an intense sympathetic neurohumoral effect.
BACKGROUND
Verapamil is an effective drug to slow ventricular rate in atrial fibrillation (AF). Clinically, however, i.v. verapamil enhances AF despite experimental evidence suggesting favorable effects of the drug on AF-induced electrical remodeling of the atria.


RESULTS
To clarify this controversy, i.v. verapamil's effects were determined in 41 anesthetized dogs, including 6 after beta-blockade. Intravenous verapamil (0.20 mg/kg, bolus, and 0.20 mg/kg/h, infusion) increased the duration of AF (induced by a single extrastimulus), from 19 +/- 6 to 130 +/- 24 s, P < 0.001, and slowed its ventricular response, from 246 +/- 25 to 110 +/- 15 min-1, P < 0.001. Mean aortic pressure, P = 0.002, and systemic vascular resistance, P < 0.035, decreased, and mean right atrial pressure increased, P < 0.001. Plasma norepinephrine concentration increased by 502 +/- 83 pg/mL, P < 0.001, plasma epinephrine concentration by 804 +/- 206 pg/mL, P = 0.002, and plasma total catecholamine concentration by 1606 +/- 366 pg/mL, P = 0.001. Prolongation of AF was related to an increase in mean right atrial pressure, R = 0.49, P = 0.014, right atrial wall tension, R = 0.45, P = 0.044, and plasma norepinephrine concentration, R = 0.83, P < 0.001, with plasma norepinephrine concentration remaining as an independent predictor of AF lengthening on multivariable analysis. In the presence of beta-blockade, verapamil produced comparable or more exaggerated hemodynamic effects, but it did not promote AF.


CONCLUSIONS
The prolongation of AF by verapamil can be related directly to the intense sympathetic neurohumoral effect that occurs following the drug's administration.
Friedman
H S
HS
Department of Medicine, Long Island College Hospital, USA.
Rodney
E
E
Sinha
B
B
Sharafkhaneh
A
A
Wattanasuwan
N
N
Win
M
M
Mallipeddi
D
D
Sinha
A
A
Hussain
A
A
Dai
C P
CP
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000097:blood / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004594:Electrophysiology; D004837:Epinephrine / Q000097:blood; D006321:Heart / Q000294:innervation* / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D002395:Catecholamines; D014700:Verapamil; D009638:Norepinephrine; D004837:Epinephrine