Kharche, S. R., Stary, T., Colman, M. A., Biktasheva, I. V., Workman, A. J. , Rankin, A. C., Holden, A. V. and Zhang, H. (2014) Effects of human atrial ionic remodelling by β-blocker therapy on mechanisms of AF: a computer simulation. Europace, 16(10), pp. 1524-1533. (doi: 10.1093/europace/euu084) (PMID:25085203) (PMCID:PMC4640177)
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Abstract
Aims: Atrial anti-arrhythmic effects of β-adrenoceptor antagonists (β-blockers) may involve both a suppression of pro-arrhythmic effects of catecholamines, and an adaptational electrophysiological response to chronic β-blocker use; so-called ‘pharmacological remodelling’. In human atrium, such remodelling decreases the transient outward (Ito) and inward rectifier (IK1) K+ currents, and increases the cellular action potential duration (APD) and effective refractory period (ERP). However, the consequences of these changes on mechanisms of genesis and maintenance of atrial fibrillation (AF) are unknown. Using mathematical modelling, we tested the hypothesis that the long-term adaptational decrease in human atrial Ito and IK1 caused by chronic β-blocker therapy, i.e. independent of acute electrophysiological effects of β-blockers, in an otherwise un-remodelled atrium, could suppress AF.<p></p> Methods and results: Contemporarily, biophysically detailed human atrial cell and tissue models were used to investigate effects of the β-blocker-based pharmacological remodelling. Chronic β-blockade remodelling prolonged atrial cell APD and ERP. The incidence of small amplitude APD alternans in the CRN model was reduced. At the 1D tissue level, β-blocker remodelling decreased the maximum pacing rate at which APs could be conducted. At the three-dimensional organ level, β-blocker remodelling reduced the life span of re-entry scroll waves.<p></p> Conclusion: This study improves our understanding of the electrophysiological mechanisms of AF suppression by chronic β-blocker therapy. Atrial fibrillation suppression may involve a reduced propensity for maintenance of re-entrant excitation waves, as a consequence of increased APD and ERP.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Rankin, Professor Andrew and Workman, Dr Antony |
| Authors: | Kharche, S. R., Stary, T., Colman, M. A., Biktasheva, I. V., Workman, A. J., Rankin, A. C., Holden, A. V., and Zhang, H. |
| Subjects: | Q Science > QP Physiology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Europace |
| Publisher: | Oxford University Press |
| ISSN: | 1099-5129 |
| ISSN (Online): | 1532-2092 |
| Published Online: | 01 August 2014 |
| Copyright Holders: | Copyright © 2014 The Authors |
| First Published: | First published in Europace 16(10):1524-1533 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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