Mechanism for pituitary adenylate cyclase-activating polypeptide-induced atrial fibrillation.
BACKGROUND
Pituitary adenylate cyclase-activating polypeptide (PACAP), which activates intracardiac postganglionic parasympathetic nerves, has a greater profibrillatory effect than vagal stimulation. However, the mechanism responsible for this is unclear.


RESULTS
We examined the effective refractory period (ERP), conduction time, and incidence of atrial fibrillation (AF) induced by a single premature extrastimulus at four atrial sites as well as the AF cycle length at 65 atrial sites in 12 autonomically decentralized, open chest, anesthetized dogs. These parameters were measured in the control condition, during cervical vagal stimulation, and after PACAP administration. PACAP shortened the ERP to a similar extent at all four sites. Vagal stimulation shortened the ERP primarily at the high right atrium, but not at the other three sites. Global dispersion of ERP and variation in the AF cycle length (P < 0.01) were less after PACAP than during vagal stimulation. A premature extrastimulus induced AF more frequently after PACAP than during vagal stimulation (P < 0.001). The ERP at the pacing site was shorter when AF was induced than when it was not induced regardless of the intervention and the pacing site. Conduction time following premature beats that induced AF was shorter after PACAP than during vagal stimulation (P < 0.01).


CONCLUSIONS
Global ERP shortening contributes to the greater profibrillatory effect of PACAP. In addition, the decreased conduction time following premature beats may be associated with AF induction in this model.
Hirose
M
M
Division of Cardiology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Leatmanoratn
Z
Z
Laurita
K R
KR
Carlson
M D
MD
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D016275:Atrial Function / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012032:Refractory Period, Electrophysiological; D014630:Vagus Nerve
D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide