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Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description

Orini, M; Taggart, P; Srinivasan, N; Hayward, M; Lambiase, PD; (2016) Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description. PLOS ONE , 11 (9) 10.1371/journal.pone.0161765. Green open access

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Abstract

Background The restitution of the action potential duration (APDR) and conduction velocity (CVR) are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood. Methods This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves) undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed. Results This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was as high as 250 ms. Heterogeneity in conduction velocity restitution can translate into both activation and repolarization dispersion and increase cardiac instability. The proposed mathematical formulation shows an excellent agreement with the experimental data (correlation coefficient r = 0.94) and provides a useful tool for the understanding of the complex interactions between activation and repolarization restitution properties as well as between their measurements.

Type: Article
Title: Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0161765
Publisher version: http://dx.doi.org/10.1371/journal.pone.0161765
Language: English
Additional information: © 2016 Orini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ACTION-POTENTIAL DURATION, CONDUCTION-VELOCITY RESTITUTION, T-WAVE ALTERNANS, SHORT-TERM-MEMORY, VENTRICULAR-FIBRILLATION, ADRENERGIC-STIMULATION, DISCORDANT ALTERNANS, CARDIAC RESTITUTION, SPATIAL-DISPERSION, MECHANISMS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: http://discovery.ucl.ac.uk/id/eprint/1527198
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