Role of atrial tissue remodeling on rotor dynamics: An in vitro study

Andreu M. Climent, María S. Guillem, Lucia Fuentes, Peter Lee, Christian Bollensdorff, María Eugenia Fernández-Santos, Susana Suárez-Sancho, Ricardo Sanz-Ruiz, Pedro Luis Sánchez, Felipe Atienza, Francisco Fernández-Avilés

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    Abstract

    The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ±1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm2), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm2, P <0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.

    Original languageEnglish
    Pages (from-to)H1964-H1973
    JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
    Volume309
    Issue number11
    DOIs
    Publication statusPublished - 2015

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    Keywords

    • Atrial fibrillation
    • Optical mapping

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)
    • Cardiology and Cardiovascular Medicine

    Cite this

    Climent, A. M., Guillem, M. S., Fuentes, L., Lee, P., Bollensdorff, C., Fernández-Santos, M. E., Suárez-Sancho, S., Sanz-Ruiz, R., Sánchez, P. L., Atienza, F., & Fernández-Avilés, F. (2015). Role of atrial tissue remodeling on rotor dynamics: An in vitro study. American Journal of Physiology - Heart and Circulatory Physiology, 309(11), H1964-H1973. https://doi.org/10.1152/ajpheart.00055.2015