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Updated: Aug 9, 2026
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A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts
Published on: February 17, 2023
Alternans and spiral breakup in a human ventricular tissue model
K H W J ten Tusscher1, A V Panfilov
1Utrecht University, Department of Theoretical Biology, Padualaan 8, 3584 CH Utrecht, The Netherlands. khwjtuss@hotmail.com
Summary
Ventricular fibrillation (VF) may be caused by steep action potential duration (APD) restitution slopes, exceeding 1. Our study suggests this instability mechanism is plausible in human cardiac tissue.
Area of Science:
- Cardiac Electrophysiology
- Computational Biology
- Cardiovascular Research
Background:
- Ventricular fibrillation (VF) is a leading cause of sudden cardiac death.
- A leading hypothesis links VF to dynamical instabilities in action potential duration (APD) restitution.
- Instability requires APD restitution slopes exceeding 1, influenced by factors like electrotonic coupling and cardiac memory.
Purpose of the Study:
- Investigate conditions for alternans and spiral breakup in human cardiac tissue.
- Develop and apply a refined human ventricular cell model.
- Explore the role of sodium current recovery in electrical instability.
Main Methods:
- Developed a new human ventricular cell model with enhanced intracellular calcium dynamics.
- Incorporated recent experimental measurements of human APD restitution.
- Simulated electrical instability in single cells, cell rings, and 2D tissue models.
Main Results:
- Fast sodium current recovery dynamics are crucial for instability onset.
- Slower sodium recovery prolongs spiral wave rotation and blunts conduction velocity restitution.
- Steeper APD restitution slopes (up to 1.5) were necessary for instability, within experimental ranges.
Conclusions:
- Steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.
- The developed model provides insights into human cardiac electrical dynamics.
- Findings reconcile theoretical instability thresholds with experimental observations.
