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Arrhythmogenic right ventricular cardiomyopathy: considerations from in silico experiments
1Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
Frontiers in Physiology
|July 4, 2012
Summary
Arrhythmogenic right ventricular cardiomyopathy (ARVC) involves changes in gap junctions and sodium current, leading to slower electrical signal conduction. Combined effects significantly reduce conduction velocity, contributing to arrhythmias.
Area of Science:
- Cardiology
- Electrophysiology
- Biophysics
Background:
- Arrhythmogenic right ventricular cardiomyopathy (ARVC) is linked to altered gap junctions and reduced fast sodium current.
- These changes are hypothesized to slow cardiac electrical conduction, promoting arrhythmias.
Purpose of the Study:
- To quantify the conduction slowing caused by gap junction remodeling and sodium current downregulation in ARVC.
- To assess the combined impact of these factors on cardiac electrical propagation.
Main Methods:
- Simulated action potential propagation in human ventricular cell models.
- Investigated effects of altered gap junctional conductance and sodium current on conduction velocity.
- Modeled both longitudinal (end-to-end) and transverse (side-by-side) cell arrangements.
Main Results:
- A 50% reduction in gap junctions decreased longitudinal conduction velocity by 11% and transverse by 29%.
- Downregulation of sodium current (50% decrease, -15mV inactivation shift) reduced conduction velocity by 32%.
- Combined factors reduced longitudinal conduction by 40% and transverse by 52%.
Conclusions:
- Gap junction remodeling and sodium current downregulation demonstrably slow cardiac conduction.
- Heterogeneity in gap junction remodeling, coupled with sodium current changes, appears critical for ARVC arrhythmogenesis.
- Gap junction remodeling alone may be less critical than its interaction with sodium current alterations.
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