Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias

Daisuke Sato, Lai Hua Xie, Ali A. Sovari, Diana X. Tran, Norishige Morita, Fagen Xie, Hrayr Karagueuzian, Alan Garfinkel, James N. Weiss, Zhilin Qu

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

The synchronization of coupled oscillators plays an important role in many biological systems, including the heart. In heart diseases, cardiac myocytes can exhibit abnormal electrical oscillations, such as early afterdepolarizations (EADs), which are associated with lethal arrhythmias. A key unanswered question is how cellular EADs partially synchronize in tissue, as is required for them to propagate. Here, we present evidence, from computational simulations and experiments in isolated myocytes, that irregular EAD behavior is dynamical chaos. We then show in electrically homogeneous tissue models that chaotic EADs synchronize globally when the tissue is smaller than a critical size. However, when the tissue exceeds the critical size, electrotonic coupling can no longer globally synchronize EADs, resulting in regions of partial synchronization that shift in time and space. These regional partially synchronized EADs then form premature ventricular complexes that propagate into recovered tissue without EADs. This process creates multiple hat propagate "shifting" foci resembling polymorphic ventricular tachycardia. Shifting foci encountering shifting repolarization gradients can also develop localized wave breaks leading to reentry and fibrillation. As predicted by the theory, rabbit hearts exposed to oxidative stress (H2O2) exhibited multiple shifting foci causing polymorphic tachycardia and fibrillation. This mechanism explains how collective cellular behavior integrates at the tissue scale to generate lethal cardiac arrhythmias over a wide range of heart rates.

Original languageEnglish (US)
Pages (from-to)2983-2988
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number9
DOIs
StatePublished - Mar 3 2009

    Fingerprint

Keywords

  • Chaos
  • Fibrillation
  • Foci
  • Reentry

ASJC Scopus subject areas

  • General

Cite this

Sato, D., Xie, L. H., Sovari, A. A., Tran, D. X., Morita, N., Xie, F., Karagueuzian, H., Garfinkel, A., Weiss, J. N., & Qu, Z. (2009). Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias. Proceedings of the National Academy of Sciences of the United States of America, 106(9), 2983-2988. https://doi.org/10.1073/pnas.0809148106