Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart
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)...
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| Format: | Conference item |
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Institute of Electrical and Electronics Engineers
2016
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| _version_ | 1826278307506683904 |
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| author | Santos, D Orini, M Zhou, X Bueno-Orovio, A Hanson, B Taggart, P Hayward, M Rodriguez, B Lambiase, P |
| author_facet | Santos, D Orini, M Zhou, X Bueno-Orovio, A Hanson, B Taggart, P Hayward, M Rodriguez, B Lambiase, P |
| author_sort | Santos, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T23:41:59Z |
| format | Conference item |
| id | oxford-uuid:6fa13551-5798-4a74-98e2-4f9639b9930a |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:41:59Z |
| publishDate | 2016 |
| publisher | Institute of Electrical and Electronics Engineers |
| record_format | dspace |
| spelling | oxford-uuid:6fa13551-5798-4a74-98e2-4f9639b9930a2022-03-26T19:31:54ZEffects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heartConference itemhttp://purl.org/coar/resource_type/c_5794uuid:6fa13551-5798-4a74-98e2-4f9639b9930aSymplectic Elements at OxfordInstitute of Electrical and Electronics Engineers2016Santos, DOrini, MZhou, XBueno-Orovio, AHanson, BTaggart, PHayward, MRodriguez, BLambiase, PRepolarization 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. |
| spellingShingle | Santos, D Orini, M Zhou, X Bueno-Orovio, A Hanson, B Taggart, P Hayward, M Rodriguez, B Lambiase, P Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title | Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title_full | Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title_fullStr | Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title_full_unstemmed | Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title_short | Effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
| title_sort | effects and underlying mechanisms of refractory period pacing on repolarization dynamics in the human heart |
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