Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Richard H Clayton,Peter Taggart

doi:10.1186/1475-925x-4-54

Abstract

BackgroundRegional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood.MethodsWe simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution.ResultsWavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms).ConclusionRegional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve.

Highlights

Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood
Regional differences in repolarisation are often described as dispersion, and vulnerability to arrhythmias has been shown to depend on dispersion of repolarisation in both experimental [5,6] and computational studies [7,8,9,10]
This study used a simplified computational model of cardiac tissue to test the idea that regional differences in APD restitution can be a potent substrate for initiating reentrant arrhythmias

Summary

Introduction

Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. The dynamic behaviour of APD in response to cycle length changes has been shown in theoretical, experimental and computational studies to be a major determinant of wavefront stability [1,2]. Regional differences in repolarisation are often described as dispersion, and vulnerability to arrhythmias has been shown to depend on dispersion of repolarisation in both experimental [5,6] and computational studies [7,8,9,10] This conceptual link between dispersion of repolarisation and vulnerability to re-entry may make a tacit assumption that APD dispersion is a static property of the tissue, resulting from underlying heterogeneity in electrophysiology. One important consequence of this dynamic behaviour is that dispersion of repolarisation can be produced in electrophysiologically homogenous tissue if the DI is spatially non-uniform [11,12], resulting in alternans, wavebreak and re-entry

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