title: Calcium-mediated triggered activity is an underlying cellular mechanism of ectopy originating from the pulmonary vein in dogs.
abstract: Paroxysmal atrial fibrillation associated with focal ectopy originating from the pulmonary vein (PV) can be preceded by variations in autonomic tone; however, the underlying cellular mechanisms are not clear. To determine the mechanisms of autonomically mediated PV ectopy, high-resolution optical mapping techniques were used to measure action potentials and Ca(2+) transients from the PV and the ligament of Marshall area in the arterially perfused canine left atrium. Rapid pacing was used to initiate ectopic activity during pituitary adenylate cyclase-activating polypeptide (PACAP) injection (1 nmol), as a surrogate for autonomic imbalance, before (n = 9) and after (n = 6) verapamil (10 nmol) administration. In all preparations, spontaneous activity was absent before rapid pacing. During PACAP injection, rapid pacing induced ectopic activity in eight of nine preparations. In contrast, before PACAP injection, rapid pacing did not induce ectopic activity. Activation maps of each episode of ectopic activity indicated that the site of origin occurred more frequently in the PV (70%) than in the ligament of Marshall (30%) area. As rapid pacing cycle length increased, so did the ectopic beat coupling interval. In addition, PACAP-induced ectopic activity was associated with large Ca(2+) transient amplitudes and was always suppressed by verapamil, a Ca(2+) channel blocker (P < 0.05). Finally, during PACAP injection in the absence of an ectopic beat, spontaneous Ca(2+) release and delayed afterdepolarizations were observed simultaneously after termination of rapid pacing. In conclusion, these data suggest that autonomically mediated PV ectopy may be due to Ca(2+)-mediated triggered activity arising from delayed afterdepolarizations.
authors.affiliation: Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hirose
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Laurita
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology* / Q000517:prevention & control; D001341:Autonomic Nervous System / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000166:cytology; D066298:In Vitro Techniques; D008022:Ligaments; D008297:Male; D010138:Pacemaker, Artificial; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D011667:Pulmonary Veins / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014700:Verapamil; D002118:Calcium