Advanced search
1 file | 2.29 MB

Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium

Author
Organization
Abstract
Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity.
Keywords
EPICARDIAL BORDER ZONE, ACTION-POTENTIAL DURATION, MYOFIBROBLASTS, PREVENTS ARRHYTHMIAS, CONDUCTION-VELOCITY RESTITUTION, HEALING CANINE, INFARCTS, CARDIAC TISSUE, GAP-JUNCTIONS, COMPUTER-SIMULATION, IN-VITRO, CONNEXIN43

Downloads

  • MajumderPanfilovFibrosisSciRep16.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 2.29 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Majumder, Rupamanjari, Marc C Engels, Antoine AF de Vries, Alexander Panfilov, and Daniel A Pijnappels. 2016. “Islands of Spatially Discordant APD Alternans Underlie Arrhythmogenesis by Promoting Electrotonic Dyssynchrony in Models of Fibrotic Rat Ventricular Myocardium.” Scientific Reports 6.
APA
Majumder, R., Engels, M. C., de Vries, A. A., Panfilov, A., & Pijnappels, D. A. (2016). Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Majumder R, Engels MC, de Vries AA, Panfilov A, Pijnappels DA. Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium. SCIENTIFIC REPORTS. 2016;6.
MLA
Majumder, Rupamanjari et al. “Islands of Spatially Discordant APD Alternans Underlie Arrhythmogenesis by Promoting Electrotonic Dyssynchrony in Models of Fibrotic Rat Ventricular Myocardium.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{8520509,
  abstract     = {Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity.},
  articleno    = {24334},
  author       = {Majumder, Rupamanjari and Engels, Marc C and de Vries, Antoine AF and Panfilov, Alexander and Pijnappels, Daniel A},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keywords     = {EPICARDIAL BORDER ZONE,ACTION-POTENTIAL DURATION,MYOFIBROBLASTS,PREVENTS ARRHYTHMIAS,CONDUCTION-VELOCITY RESTITUTION,HEALING CANINE,INFARCTS,CARDIAC TISSUE,GAP-JUNCTIONS,COMPUTER-SIMULATION,IN-VITRO,CONNEXIN43},
  language     = {eng},
  pages        = {12},
  title        = {Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium},
  url          = {http://dx.doi.org/10.1038/srep24334},
  volume       = {6},
  year         = {2016},
}

Altmetric
View in Altmetric
Web of Science
Times cited: