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This Article Full Text Full Text (PDF) All Versions of this Article: 292/4/H1861    most recent 00826.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Hirose, M. Articles by Laurita, K. R. Search for Related Content PubMed PubMed Citation Articles by Hirose, M. Articles by Laurita, K. R.

Calcium-mediated triggered activity is an underlying cellular mechanism of ectopy originating from the pulmonary vein in dogs

¹Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano, Japan; and ²Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, Ohio

Submitted 1 August 2006 ; accepted in final form 4 December 2006

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 Ca²⁺ 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 Ca²⁺ transient amplitudes and was always suppressed by verapamil, a Ca²⁺ channel blocker (P < 0.05). Finally, during PACAP injection in the absence of an ectopic beat, spontaneous Ca²⁺ 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 Ca²⁺-mediated triggered activity arising from delayed afterdepolarizations.

delayed afterdepolarizations; pituitary adenylate cyclase-activating polypeptide; ligament of Marshall; high-resolution optical mapping

This article has been cited by other articles:

				B. S. Stambler and K. R. Laurita Atrial Fibrillation in Heart Failure: Steady Progress but Still a Long Way to Go Circ Arrhythm Electrophysiol, June 1, 2008; 1(2): 77 - 79. [Full Text] [PDF]