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This Article Full Text Full Text (PDF) All Versions of this Article: 91/2/339    most recent expphysiol.2005.031070v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nash, M. P. Articles by Taggart, P. Search for Related Content PubMed PubMed Citation Articles by Nash, M. P. Articles by Taggart, P. Related Collections Heart/Cardiac Muscle

¹ Bioengineering Institute and Engineering Science, University of Auckland, New Zealand² Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy & Genetics, University of Oxford, UK³ Departments of Cardiology and Cardiothoracic Surgery, University College Hospital, London, UK⁴ Department of Computer Science, University of Sheffield, UK

Steep action potential duration (APD) restitution has been shown to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined clinical electrophysiology and computer 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. In 14 patients aged 52–85 years undergoing routine cardiac surgery, 256 electrode epicardial mapping was performed. 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. 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. Eleven per cent of restitution curves maintained slope > 1 over a range of diastolic intervals of at least 30 ms; and 0.3% for at least 50 ms. Activation–recovery interval restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. We used a simplified computer model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to, and stability of re-entry. Our model showed that heterogeneity of restitution can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Global epicardial mapping in humans showed that APD restitution slopes were organized into regions of shallow and steep slopes. This heterogeneous organization of restitution may provide a substrate for arrhythmia.

(Received 31 October 2005; accepted after revision 10 January 2006; first published online 1 February 2006)
Corresponding author P. Taggart: Departments of Cardiology and Cardiothoracic Surgery, University College Hospital, 16–18 Westmoreland Street, London W1G 8PH, UK. Email: peter.taggart{at}uclh.nhs.uk