Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015 (2015), Article ID 496418, 18 pages
http://dx.doi.org/10.1155/2015/496418
Research Article

Chronotropic Modulation of the Source-Sink Relationship of Sinoatrial-Atrial Impulse Conduction and Its Significance to Initiation of AF: A One-Dimensional Model Study

1Department of Life Sciences, University of Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy
2Center of Excellence for Toxicological Research (CERT), Department of Clinical and Experimental Medicine, University of Parma, Via Gramsci 14, 43126 Parma, Italy

Received 5 December 2014; Revised 25 February 2015; Accepted 10 March 2015

Academic Editor: Alexey V. Glukhov

Copyright © 2015 Francesca Cacciani and Massimiliano Zaniboni. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation , which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in . Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies.