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April 16, 1999Circulation Research359 citationsOpen Access

Molecular Mechanisms of Ionic Remodeling in Atrial Fibrillation in Dogs

Molecular Mechanisms Underlying Ionic Remodeling in a Dog Model of Atrial Fibrillation

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Why the study?

Does rapid atrial pacing alter cardiac ion channel gene expression in a dog model of atrial fibrillation?

Population

Dog model of atrial fibrillation

Comparison

Atrial pacing at 400 bpm for 7 days or 42 days vs Sham controls

Design

Preclinical

Follow-up

7 or 42 days

Authors

LYLixia YuePMPeter MelnykRGRania Gaspo

Discussion

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Overview

Findings remain preclinical; leaves open whether channel downregulation perpetuates AF in patients.

Key Points

  • This research aims to investigate how atrial fibrillation affects gene expression related to ionic currents in a dog model.
  • Used competitive reverse transcriptase-polymerase chain reaction to measure mRNA concentrations in dogs with different durations of atrial pacing and controls.
  • Conducted Western blot analysis to quantify protein levels of ion channel subunits.
  • Examined the relationship between gene expression, protein levels, and ionic current densities.
  • Kv4.3 gene expression decreased by 60% in 7-day dogs and 74% in 42-day dogs (P<0.01 and P<0.001).
  • L-type Ca2+ channel gene decreased by 57% in P7 and 72% in P42 (P<0.01 compared to controls).
  • Na+ channel subunit gene expression reduced by 18% in P7 and 42% in P42 with significant changes for P42 (P<0.01).

Structured PICO

Does rapid atrial pacing alter cardiac ion channel gene expression in a dog model of atrial fibrillation?

P
Population
Dog model of atrial fibrillation
I
Intervention
Atrial pacing at 400 bpm for 7 days (group P7) or 42 days (group P42)
C
Comparator
Sham controls
O
Outcome
mRNA concentrations of Kv4.3, alpha1c subunit of L-type Ca2+ channels, and alpha subunit of cardiac Na+ channelssurrogate

Chronic atrial tachycardia downregulates the gene and protein expression of key atrial ion channels, providing a molecular mechanism for the self-perpetuating nature of atrial fibrillation.

Cite This Study

Yue et al. (1999) studied this question.

synapsesocial.com/papers/6a1997cc7081f56b37decd40https://doi.org/10.1161/01.res.84.7.776
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