Effects of human atrial ionic remodelling by β-blocker therapy on mechanisms of atrial fibrillation: a computer simulation
| Autor: | Arun V. Holden, Antony J. Workman, Irina V. Biktasheva, Sanjay Kharche, Henggui Zhang, Michael A. Colman, Tomas Stary, Andrew C. Rankin |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Adrenergic beta-Antagonists Action Potentials 030204 cardiovascular system & hematology Ion Channels Article 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Atrial Fibrillation medicine Humans Computer Simulation 030304 developmental biology 0303 health sciences Atrium (architecture) Inward-rectifier potassium ion channel business.industry Effective refractory period Atrial fibrillation Atrial Remodeling medicine.disease Small amplitude Electrophysiology cardiovascular system Cardiology Action potential duration Cardiology and Cardiovascular Medicine business |
| Zdroj: | EP Europace. 16:1524-1533 |
| ISSN: | 1532-2092 1099-5129 |
| Popis: | 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 ( I to) and inward rectifier ( I K1) 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 I to and I K1 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. 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. 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. |
| Databáze: | OpenAIRE |
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