Stochastic spontaneous calcium release events and sodium channelopathies promote ventricular arrhythmias
| Autor: | Yohannes Shiferaw, Edward J. Vigmond, Fernando O. Campos, Gernot Plank |
|---|---|
| Přispěvatelé: | Deutsches Herzzentrum Berlin, Medical University Graz, Modélisation et calculs pour l'électrophysiologie cardiaque (CARMEN), IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), European Space Research and Technology Centre (ESTEC), European Space Agency (ESA), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-IHU-LIRYC, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Agence Spatiale Européenne = European Space Agency (ESA) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Purkinje fibers Sodium Heart Ventricles General Physics and Astronomy chemistry.chemical_element Action Potentials 030204 cardiovascular system & hematology Calcium behavioral disciplines and activities Purkinje Fibers 03 medical and health sciences 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Heart Conduction System Internal medicine medicine Myocyte Animals Focus Issue: Complex Cardiac Dynamics Computer Simulation Myocytes Cardiac cardiovascular diseases Mathematical Physics Calcium metabolism Stochastic Processes business.industry Applied Mathematics Models Cardiovascular Statistical and Nonlinear Physics Arrhythmias Cardiac Reentry Ventricular Premature Complexes Electrophysiology 030104 developmental biology medicine.anatomical_structure chemistry Cardiology cardiovascular system Channelopathies Rabbits Electrical conduction system of the heart business |
| Zdroj: | Chaos Chaos: An Interdisciplinary Journal of Nonlinear Science Chaos: An Interdisciplinary Journal of Nonlinear Science, American Institute of Physics, 2017, 27 (9), pp.093910. ⟨10.1063/1.4999612⟩ Chaos: An Interdisciplinary Journal of Nonlinear Science, 2017, 27 (9), pp.093910. ⟨10.1063/1.4999612⟩ |
| ISSN: | 1089-7682 1054-1500 |
| DOI: | 10.1063/1.4999612⟩ |
| Popis: | International audience; Premature ventricular complexes (PVCs), the first initiating beats of a variety of cardiac arrhythmias, have been associated with spontaneous calcium release (SCR) events at the cell level. However, the mechanisms underlying the degeneration of such PVCs into arrhythmias are not fully understood. The objective of this study was to investigate the conditions under which SCR-mediated PVCs can lead to ventricular arrhythmias. In particular, we sought to determine whether sodium (Na+) current loss-of-function in the structurally normal ventricles provides a substrate for unidirectional conduction block and reentry initiated by SCR-mediated PVCs. To achieve this goal, a stochastic model of SCR was incorporated into an anatomically accurate compute model of the rabbit ventricles with the His-Purkinje system (HPS). Simulations with reduced Na+ current due to a negative-shift in the steady-state channel inactivation showed that SCR-mediated delayed afterdepolarizations led to PVC formation in the HPS, where the electrotonic load was lower, conduction block, and reentry in the 3D myocardium. Moreover, arrhythmia initiation was only possible when intrinsic electrophysiological heterogeneity in action potential within the ventricles was present. In conclusion, while benign in healthy individuals SCR-mediated PVCs can lead to life-threatening ventricular arrhythmias when combined with Na+ channelopathies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|