Received October 31, 2005
Revised December 5, 2005
Accepted after revision January 10, 2006

¹ University of Auckland
² University of Oxford
³ University College Hospital London
⁴ University of Sheffield

^* To whom correspondence should be addressed. E-mail: martyn.nash{at}auckland.ac.nz.

	Abstract

Objectives: Steep APD restitution has been shown experimentally to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined a clinical electrophysiology and modelling study to (1) determine global APD restitution properties in cardiac patients and (2) examine the interaction of the observed APD restitution with known arrhythmia mechanisms. Methods: 256 electrode epicardial mapping was performed in 14 patients aged 52-85 years undergoing surgery for coronary artery disease (CAD; n=8) or aortic valve disease (AVD; n=6; no significant CAD), at low risk of ventricular arrhythmia based on clinical criteria. Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the entire ventricular surface. Mono-exponential restitution curves were constructed for each electrode site using a standard S1-S2 pacing protocol. We used a simplified computer model of 2D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to and stability of re-entry. Results: The median maximum restitution slope was 0.91, with 27% of all electrode sites with slopes < 0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. 11% of restitution curves maintained a slope >1 over a range of diastolic intervals of at least 30ms; and 0.3% for at least 50ms. ARI restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. Our model showed that this type of heterogeneity can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Conclusions: Global epicardial mapping in humans showed that APD restitution slopes were organised into regions of shallow and steep slopes. This heterogeneous organisation of restitution may provide substrate for arrhythmia.

Key Words: Action potential, Cardiac arrhythmia, Electrophysiology

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