Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers Articles uri icon

authors

  • GOMEZ CID, LIDIA
  • DEL CANTO, IRENE
  • HERNANDEZ ROMERO, ISMAEL
  • GUILLEM, MARIA S.
  • FERNÁNDEZ SANTOS, MARÍA EUGENIA
  • ATIENZA, FELIPE
  • SUCH, LUIS
  • FERNÁNDEZ AVILÉS, FRANCISCO
  • CHORRO, FRANCISCO J.
  • CLIMENT, ANDREU M.

publication date

  • August 2020

start page

  • 1

end page

  • 13

issue

  • 922

volume

  • 11

International Standard Serial Number (ISSN)

  • 1664-042X

abstract

  • Background: Mechanical stretch increases NaC inflow into myocytes, related to
    mechanisms including stretch-activated channels or NaC/HC exchanger activation,
    involving Ca2C increase that leads to changes in electrophysiological properties favoring
    arrhythmia induction. Ranolazine is an antianginal drug with confirmed beneficial effects
    against cardiac arrhythmias associated with the augmentation of INaL current and
    Ca2C overload.
    Objective: This study investigates the effects of mechanical stretch on activation
    patterns in atrial cell monolayers and its pharmacological response to ranolazine.
    Methods: Confluent HL-1 cells were cultured in silicone membrane plates and were
    stretched to 110% of original length. The characteristics of in vitro fibrillation (dominant
    frequency, regularity index, density of phase singularities, rotor meandering, and rotor
    curvature) were analyzed using optical mapping in order to study the mechanoelectric
    response to stretch under control conditions and ranolazine action.
    Results: HL-1 cell stretch increased fibrillatory dominant frequency (3.65  0.69 vs.
    4.35  0.74 Hz, p < 0.01) and activation complexity (1.97  0.45 vs. 2.66  0.58
    PS/cm2, p < 0.01) under control conditions. These effects were related to stretchinduced
    changes affecting the reentrant patterns, comprising a decrease in rotor
    meandering (0.72  0.12 vs. 0.62  0.12 cm/s, p < 0.001) and an increase in wavefront
    curvature (4.90  0.42 vs. 5.68  0.40 rad/cm, p < 0.001). Ranolazine reduced stretchinduced
    effects, attenuating the activation rate increment (12.8% vs. 19.7%, p < 0.01)
    and maintaining activation complexity¿both parameters being lower during stretch than
    under control conditions. Moreover, under baseline conditions, ranolazine slowed and
    regularized the activation patterns (3.04  0.61 vs. 3.65  0.69 Hz, p < 0.01).
    Conclusion: Ranolazine attenuates the modifications of activation patterns induced by
    mechanical stretch in atrial myocyte monolayers.

subjects

  • Biology and Biomedicine

keywords

  • mechanical stretch; mechanoelectric feedback; fibrillatory patterns; ranolazine; optical mapping; rotor dynamic analysis; hl-1 cell