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Spatially discordant alternans in cardiomyocyte monolayers
Carlos de Diego1, Rakesh K Pai, Amish S Dave
1Cardiovascular Research Laboratory, Department of Medicine, Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|January 29, 2008
Summary
Spatially discordant repolarization alternans, a precursor to sudden cardiac death, can be readily induced in two-dimensional cardiac tissue. This study shows these alternans are primarily dynamically generated, not due to tissue differences.
Area of Science:
- Cardiac Electrophysiology
- Computational Biology
- Cardiovascular Research
Background:
- Repolarization alternans, characterized by beat-to-beat variations in action potential duration (APD) and intracellular calcium (Cai), can precede sudden cardiac death.
- Spatially discordant alternans are particularly dangerous, but distinguishing their origins (tissue heterogeneity vs. dynamic factors) in complex 3D cardiac tissue is challenging.
Purpose of the Study:
- To investigate repolarization alternans in a simplified 2D cardiac model to better understand the underlying mechanisms.
- To evaluate the role of dynamic factors versus tissue heterogeneities in the generation of spatially discordant alternans.
Main Methods:
- Optical mapping of voltage and Cai in cultured neonatal rat ventricular myocyte monolayers.
- Rapid pacing protocols were employed, both before and after exposure to BAY K 8644 to enhance dynamic factors.
- Analysis of alternans development, spatial discordance, nodal line behavior, and conduction block.
Main Results:
- Under control conditions, 81% of monolayers showed APD alternans and 100% showed Cai alternans, with 62% becoming spatially discordant.
- After BAY K 8644, all monolayers exhibited spatially discordant APD and Cai alternans, with increased nodal lines.
- Nodal line behavior (movement and orientation changes) supported a dynamically generated mechanism for alternans.
Conclusions:
- Spatially discordant alternans, capable of inducing reentry, can be easily generated in 2D cardiac tissue through rapid pacing.
- The observed behavior strongly suggests that dynamic factors play a predominant role in the generation of these alternans, rather than inherent tissue heterogeneities.
