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Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart

Santos, D; Orini, M; Zhou, X; Bueno-Orovio, A; Hanson, B; Taggart, P; Hayward, M; ... Taggart, P; + view all (2016) Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart. In: Wheeler, B and Wang, MD, (eds.) 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2016): Proceedings. (pp. pp. 157-160). Institute of Electrical and Electronics Engineers (IEEE) Green open access

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Abstract

Repolarization alternans is related to the initiation of life threatening cardiac arrhythmias. Experimental and computational studies suggest that the abolishment of alternans using dynamic pacing protocols may prevent abnormal heart rhythms. In a recent animal study, refractory period pacing (RPP) on every other beat has shown promising results in alternans reduction. However, the cellular mechanisms underlying this therapy and its efficiency in human patients remain unclear. In this study, in vivo unipolar electrograms acquired during RPP from 240 epicardial sites from one patient were analysed. Current clamp of 18 channels was performed in silico to elucidate the ionic mechanisms underlying action potential modulation by RPP. Its efficacy with positive and negative polarities was tested on a population of 87 calibrated human ventricular models exhibiting alternans. In vivo electrograms showed significant changes in T-wave alternans when applying RPP. In silico, results showed APD shortening for RPP with positive polarity and APD prolongation with RPP negative. Under current clamp protocols, voltage rectification of L-type Ca(2)+ (ICaL) and inward rectifier K+ (IK1) currents were identified as the key determinants for the observed changes. RPP pacing successfully reduced alternans on the in silico models using a negative polarity stimulus in the short beat.

Type: Proceedings paper
Title: Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart
Event: EMBC 2016: 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 16-20 August 2016, Orlando, Florida, USA
Location: United States
ISBN-13: 9781457702204
Open access status: An open access version is available from UCL Discovery
DOI: 10.1109/EMBC.2016.7590664
Publisher version: https://doi.org/10.1109/EMBC.2016.7590664
Language: English
Additional information: Copyright © 2016 IEEE. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Avalanche photodiodes, Protocols, Heart, Clamps, Computational modeling, In vivo, Sociology
UCL classification: UCL
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 Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
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: https://discovery.ucl.ac.uk/id/eprint/1539797
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