Key result
Simulated downregulation of G Kr (class III antiarrhythmics) increased the safety factor for pacemaker-to-atrial action potential conduction, accompanied by decreased conduction delay.
Why the study?
Do simulated chronotropic interventions affect the safety factor for pacemaker-to-atrial action potential conduction in a one-dimensional model?
Do simulated chronotropic interventions affect the safety factor for pacemaker-to-atrial action potential conduction in a one-dimensional model?
Simulated class III antiarrhythmic agents (downregulation of G Kr) increase the safety factor for pacemaker-to-atrial conduction, potentially offering insights into anti-AF strategies.
Hypothesis-generating for class III agents in atrial conduction; clinical translation and anti-AF utility require prospective study.
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 G Kr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in I CaL. 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.
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Cacciani et al. (2015) studied Atrial fibrillation. Simulated chronotropic interventions (e.g., Ivabradine, class III antiarrhythmics) vs. Control conditions was evaluated on Safety factor for pacemaker-to-atrial AP conduction (SASF). Simulated downregulation of G Kr (class III antiarrhythmics) increased the safety factor for pacemaker-to-atrial action potential conduction, accompanied by decreased conduction delay.
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