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Updated: Jul 8, 2025
A Cardiac Microphysiological System for Studying Ca2+ Propagation via Non-genetic Optical Stimulation
Published on: March 21, 2025
In silico optical modulation of spiral wave trajectories in cardiac tissue
Sayedeh Hussaini1,2, Rupamanjari Majumder3,4, Valentin Krinski4
1Institute of Pharmacology and Toxicology, University Medical Center Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Niedersachsen, Germany. sayedeh.hussaini@ds.mpg.de.
Insights
Computational cardiac optogenetics reveals new ways to control spiral wave dynamics in the heart. This research offers insights into optimizing defibrillation for treating life-threatening cardiac arrhythmias.
Area of Science:
- Computational biology
- Cardiac electrophysiology
- Optogenetics
Background:
- Life-threatening cardiac arrhythmias, like ventricular tachycardia and fibrillation, are linked to abnormal electrical spiral waves in the heart, often leading to sudden cardiac death.
- Current treatments like defibrillation, while effective, have negative side effects, highlighting the need for improved arrhythmia control strategies.
- Understanding spiral wave dynamics is crucial for optimizing therapeutic interventions.
Purpose of the Study:
- To investigate and control the dynamics of a single spiral wave in a computational model of a mouse ventricle using optogenetics.
- To explore the effects of different optical stimulation frequencies on spiral wave trajectories.
- To develop and test a resonant feedback pacing method for steering spiral wave behavior.
Main Methods:
- Utilized a detailed, light-sensitive computational model of a mouse ventricle.
- Applied periodic optical pulses in the sub-threshold regime to observe spiral wave core trajectories.
- Implemented resonant feedback pacing, triggering optical pulses based on real-time membrane voltage measurements.
Main Results:
- Observed various spiral wave core drift trajectories, including epicycloidal, hypocycloidal, and resonant patterns, under global optical stimulation.
- Demonstrated successful steering of spiral wave dynamics using resonant feedback pacing, controlled by electrode position.
- Provided mechanistic insights into the efficacy of optical stimulation for arrhythmia control.
Conclusions:
- Computational cardiac optogenetics offers a powerful tool for studying and manipulating cardiac spiral wave dynamics.
- Resonant feedback pacing presents a promising method for targeted control of spiral waves, potentially leading to more effective arrhythmia therapies.
- This study enhances understanding of optical stimulation's role in managing cardiac arrhythmias and improving defibrillation strategies.
Abstract:
Life-threatening cardiac arrhythmias such as ventricular tachycardia and fibrillation are common precursors to sudden cardiac death. They are associated with the occurrence of abnormal electrical spiral waves in the heart that rotate at a high frequency. In severe cases, arrhythmias are combated with a clinical method called defibrillation, which involves administering a single global high-voltage shock to the heart to reset all its activity and restore sinus rhythm. Despite its high efficiency in controlling arrhythmias, defibrillation is associated with several negative side effects that render the method suboptimal. The best approach to optimize this therapeutic technique is to deepen our understanding of the dynamics of spiral waves. Here, we use computational cardiac optogenetics to study and control the dynamics of a single spiral wave in a two-dimensional, electrophysiologically detailed, light-sensitive model of a mouse ventricle. First, we illuminate the domain globally by applying a sequence of periodic optical pulses with different frequencies in the sub-threshold regime where no excitation wave is induced. In doing so, we obtain epicycloidal, hypocycloidal, and resonant drift trajectories of the spiral wave core. Then, to effectively control the wave dynamics, we use a method called resonant feedback pacing. In this approach, each global optical pulse is applied when the measuring electrode positioned on the domain registers a predefined value of the membrane voltage. This enables us to steer the spiral wave in a desired direction determined by the position of the electrode. Our study thus provides valuable mechanistic insights into the success or failure of global optical stimulation in executing efficient arrhythmia control.
