Basic/Translational Science -> Computer Modeling/Simulation D-AB20 - New Mechanistic Insights on Arrhythmia Initiation and Perpetuation (ID 40) Abstract

D-AB20-06 - Subthreshold Delayed Afterdepolarizations Represent A Substrate For Reentry Induction In The Infarcted Heart (ID 784)

 F.O. Campos: Nothing relevant to disclose.


Background: Delayed afterdepolarizations (DADs) due to spontaneous calcium release (SCR) events have been implicated in a variety of arrhythmias. While the role of DADs in forming ectopic beats has been characterized, the arrhythmogenic potential of subthreshold DADs in the infarcted border zone (BZ) remains unknown.
Objective: To use computational modelling to investigate whether subthreshold DADs may form a substrate for conduction block and reentry in the infarcted BZ.
Methods: A computational model of the porcine post-infarction heart was constructed based on MRI data. Cells in the BZ were made prone to DADs described by a phenomenological model of SCR events. The model was pre-paced (1Hz) at the base followed by a 1500ms-pacing pause to see whether DADs would emerge. An extra beat with different coupling intervals (CIs) was then applied. Sodium channel loss-of-function due to a (2.5mV and 5mV) negative-shift in the steady-state channel inactivation was also simulated to assess its arrhythmogenic potential when combined with DADs.
Results: Figure A shows DADs arising in the BZ 1070ms after the last paced beat. Next, extra beats with different CIs were simulated. In the control electrophysiological setup, simulations with extra beats did not result in block. However, when combined with a 5mV-shift in sodium channel inactivation, block and reentry at the larger transmural isthmus were detected for an extra beat with CI = 925ms (see Figure B-C).
Conclusion: Under physiological conditions, subthreshold DADs are unlikely to provide a substrate for block. However, under conditions of decreased excitability, they can cause conduction block and reentry in the infarcted region.