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Dynamical mechanism for subcellular alternans in cardiac myocytes
Stephen A Gaeta1, Gil Bub, Geoffrey W Abbott
1Greenberg Division of Cardiology, Weill Cornell Medical College, New York 10065, USA.
Circulation Research
|July 25, 2009
Summary
Researchers demonstrated a new pacing method to dynamically induce subcellular alternans in cardiac myocytes, offering new insights into arrhythmogenic mechanisms. This finding provides the first direct experimental evidence for dynamic induction of subcellular alternans.
Area of Science:
- Cardiology
- Computational Biology
- Electrophysiology
Background:
- Cardiac repolarization alternans is a dangerous heart rhythm disturbance.
- Subcellular alternans, where different parts of a cell beat differently, are observed but poorly understood.
- Previous theories suggested a dynamic mechanism, but lacked experimental proof, with most studies focusing on fixed cell differences.
Purpose of the Study:
- To generalize a dynamic mechanism for subcellular alternans.
- To develop a pacing algorithm to induce subcellular alternans in isolated cardiac myocytes.
- To verify this mechanism computationally and experimentally, and explore its role in intact heart tissue.
Main Methods:
- Developed a physiologically realistic computational model of a cardiac myocyte.
- Designed and tested a specific pacing algorithm.
- Used real-time electrophysiology and fluorescent calcium imaging in isolated guinea pig ventricular myocytes.
- Employed computational modeling to simulate tissue-level pacing.
Main Results:
- The computational model confirmed the pacing algorithm's ability to induce subcellular alternans.
- Experiments successfully and robustly induced subcellular alternans in isolated myocytes using the new protocol.
- Computational simulations showed dynamic induction of subcellular alternans during tissue-level spatially discordant alternans.
Conclusions:
- This study provides the first direct experimental evidence for the dynamic induction of subcellular alternans in cardiac myocytes.
- The proposed dynamic mechanism is a significant factor in subcellular alternans formation.
- This mechanism may contribute to arrhythmogenesis in the intact heart.
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