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Dynamical mechanism for subcellular alternans in cardiac myocytes.

Publication ,  Journal Article
Gaeta, SA; Bub, G; Abbott, GW; Christini, DJ
Published in: Circ Res
August 14, 2009

RATIONALE: Cardiac repolarization alternans is an arrhythmogenic rhythm disturbance, manifested in individual myocytes as a beat-to-beat alternation of action potential durations and intracellular calcium transient magnitudes. Recent experimental studies have reported "subcellular alternans," in which distinct regions of an individual cell are seen to have counterphase calcium alternations, but the mechanism by which this occurs is not well understood. Although previous theoretical work has proposed a possible dynamical mechanism for subcellular alternans formation, no direct evidence for this mechanism has been reported in vitro. Rather, experimental studies have generally invoked fixed subcellular heterogeneities in calcium-cycling characteristics as the mechanism of subcellular alternans formation. OBJECTIVE: In this study, we have generalized the previously proposed dynamical mechanism to predict a simple pacing algorithm by which subcellular alternans can be induced in isolated cardiac myocytes in the presence or absence of fixed subcellular heterogeneity. We aimed to verify this hypothesis using computational modeling and to confirm it experimentally in isolated cardiac myocytes. Furthermore, we hypothesized that this dynamical mechanism may account for previous reports of subcellular alternans seen in statically paced, intact tissue. METHODS AND RESULTS: Using a physiologically realistic computational model of a cardiac myocyte, we show that our predicted pacing algorithm induces subcellular alternans in a manner consistent with theoretical predictions. We then use a combination of real-time electrophysiology and fluorescent calcium imaging to implement this protocol experimentally and show that it robustly induces subcellular alternans in isolated guinea pig ventricular myocytes. Finally, we use computational modeling to demonstrate that subcellular alternans can indeed be dynamically induced during static pacing of 1D fibers of myocytes during tissue-level spatially discordant alternans. CONCLUSION: Here we provide the first direct experimental evidence that subcellular alternans can be dynamically induced in cardiac myocytes. This proposed mechanism may contribute to subcellular alternans formation in the intact heart.

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Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

August 14, 2009

Volume

105

Issue

4

Start / End Page

335 / 342

Location

United States

Related Subject Headings

  • Myocytes, Cardiac
  • Models, Cardiovascular
  • Humans
  • Heart Ventricles
  • Guinea Pigs
  • Cells, Cultured
  • Cardiovascular System & Hematology
  • Calcium
  • Animals
  • Action Potentials
 

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Gaeta, S. A., Bub, G., Abbott, G. W., & Christini, D. J. (2009). Dynamical mechanism for subcellular alternans in cardiac myocytes. Circ Res, 105(4), 335–342. https://doi.org/10.1161/CIRCRESAHA.109.197590
Gaeta, Stephen A., Gil Bub, Geoffrey W. Abbott, and David J. Christini. “Dynamical mechanism for subcellular alternans in cardiac myocytes.Circ Res 105, no. 4 (August 14, 2009): 335–42. https://doi.org/10.1161/CIRCRESAHA.109.197590.
Gaeta SA, Bub G, Abbott GW, Christini DJ. Dynamical mechanism for subcellular alternans in cardiac myocytes. Circ Res. 2009 Aug 14;105(4):335–42.
Gaeta, Stephen A., et al. “Dynamical mechanism for subcellular alternans in cardiac myocytes.Circ Res, vol. 105, no. 4, Aug. 2009, pp. 335–42. Pubmed, doi:10.1161/CIRCRESAHA.109.197590.
Gaeta SA, Bub G, Abbott GW, Christini DJ. Dynamical mechanism for subcellular alternans in cardiac myocytes. Circ Res. 2009 Aug 14;105(4):335–342.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

August 14, 2009

Volume

105

Issue

4

Start / End Page

335 / 342

Location

United States

Related Subject Headings

  • Myocytes, Cardiac
  • Models, Cardiovascular
  • Humans
  • Heart Ventricles
  • Guinea Pigs
  • Cells, Cultured
  • Cardiovascular System & Hematology
  • Calcium
  • Animals
  • Action Potentials