What is the clinical evidence from this study?

Population: Atrial arrhythmia in RyR2-P2328S mutation. Intervention: Flecainide vs. Wild-type (WT) littermates. Primary outcome: Arrhythmic incidence, action potential conduction velocity, atrial effective refractory period, AP wavelength, and Na+ currents.

What question did this study set out to answer?

This research examines how flecainide affects atrial arrhythmias in RyR2-P2328S mice compared to wild-type mice.

April 7, 2015Acta PhysiologicaOpen Access

Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murineRyR2‐P2328Shearts

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Key result

Flecainide (1 μm) rescued the atrial arrhythmogenic phenotype in RyR2-P2328S mice by restoring compromised sodium currents and action potential wavelength, whereas it was pro-arrhythmic in wild-type.

Why the study?

Does flecainide influence atrial arrhythmogenicity in RyR2(S/S) mice compared to wild-type littermates?

Key Points

This research examines how flecainide affects atrial arrhythmias in RyR2-P2328S mice compared to wild-type mice.
Examined 1 μm flecainide effects on wild-type (WT) and RyR2(S/S) atria
Measured arrhythmic incidence, AP conduction velocity (CV), atrial effective refractory period (AERP), and AP wavelength (λ) using multi-electrode array recordings
Recorded Na(+) currents (INa) via loose patch clamping of superfused atria.
RyR2(S/S) mice exhibited more frequent atrial arrhythmias and slower CV compared to WT.
Flecainide had anti-arrhythmic effects in RyR2(S/S) but pro-arrhythmic effects in WT, increasing INa in RyR2(S/S) but decreasing it in WT.
Flecainide increased AERP while maintaining CV in RyR2(S/S), and reduced CV while maintaining AERP in WT.

Structured PICO

Does flecainide influence atrial arrhythmogenicity in RyR2(S/S) mice compared to wild-type littermates?

Population

Homozygous RyR2-P2328S (RyR2(S/S)) mice and wild-type (WT) littermates

Intervention

Flecainide (1 μm)

Comparator

Wild-type (WT) littermates treated with flecainide, and baseline/untreated states

Outcome

Arrhythmic incidence, action potential (AP) conduction velocity (CV), atrial effective refractory period (AERP), AP wavelength, and Na+ currents (INa)surrogate

Flecainide exerts a paradoxical anti-arrhythmic effect in RyR2-P2328S mutant atria by restoring compromised sodium currents and action potential wavelength, contrasting with its pro-arrhythmic effects in wild-type atria.

Discussion

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Implication

Flecainide effects may differ by RyR2 genotype in mice; leaves open translation to human atrial arrhythmias.

Cite This Study

Salvage et al. (2015) studied Atrial arrhythmia in RyR2-P2328S mutation. Flecainide vs. Wild-type (WT) littermates was evaluated on Arrhythmic incidence, action potential conduction velocity, atrial effective refractory period, AP wavelength, and Na+ currents. Flecainide (1 μm) rescued the atrial arrhythmogenic phenotype in RyR2-P2328S mice by restoring compromised sodium currents and action potential wavelength, whereas it was pro-arrhythmic in wild-type.

synapsesocial.com/papers/6a5fa5524fc3492583067c66 https://doi.org/10.1111/apha.12505

Topics

Persistent AF management Atrial fibrillation

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Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murineRyR2‐P2328Shearts

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Topics

Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murineRyR2‐P2328Shearts

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider