Mechanisms of stretch-induced atrial fibrillation in the presence and the absence of adrenocholinergic stimulation: Interplay between rotors and focal discharges
Received 15 January 2009; accepted 16 March 2009. published online 15 May 2009.
Background
Both atrial stretch and combined adrenocholinergic stimulation (ACS) have been shown to favor initiation and maintenance of atrial fibrillation (AF). Their respective contributions to the electrophysiological mechanism remains, however, incompletely understood.
Objective
This study endeavored to determine the mechanism of maintenance of stretch-related AF (SRAF) in the presence and absence of ACS and to assess how focal discharges interact with rotors to modify the level of complexity in the activation patterns to perpetuate AF.
Methods
Video imaging of AF dynamics was carried out using a SRAF model in isolated sheep hearts (n = 24). Pharmacological approaches were used to (1) mimic ACS with acetylcholine (1 μM) plus isoproterenol (0.03 μM), and (2) abolish triggered activity, in response to sarcoplasmic reticulum calcium release, with caffeine (5 mM, CA) or ryanodine (10 to 40 μM, RYA).
Results
In the absence of ACS, on perfusion of CA or RYA, focal discharges were abolished and SRAF was terminated in most of the cases (10 of 13 experiments). In the presence of ACS, multiple drifting rotors as well as a large number of focal discharges were identified and only 1 of 11 AF episodes was terminated.
Conclusions
In the absence of ACS, SRAF is maintained by high-frequency focal discharges that generate fibrillatory conduction and wave breaks. In the presence of ACS, SRAF dynamics is characterized by multiple high frequency rotors that are rendered unstable by spatially distributed focal discharges.
Address reprint requests and correspondence: Dr. Jérôme Kalifa, Center for Arrhythmia Research, 5025 Venture Drive, Ann Arbor, Michigan 48108
This work was supported in part by National Heart Lung and Blood Institute grants PO1 HL039707, PO1 HL087226, and RO1 HL070074 to Dr. Jalife; RO1-HL087055 and ACCF/GE Healthcare Career Development Award to Dr. Kalifa; Heart Rhythm Society Fellowship Award 2007-8, the Suzuken Memorial Foundation 2006-7, the Kowa Life Science Foundation 2006 to Dr. Yamazaki; and a grant from the Centro Nacional de Investigaciones Cardiovasculares (CNIC) of Spain (Dr. Jalife).
The authors thank Jianling Deng and Jiang Jiang for their technical assistance.
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