Stabilizing Cardiac Ryanodine Receptor With Dantrolene Treatment Prevents Binge Alcohol-Enhanced Atrial Fibrillation...

Area of Science:

• Cardiology
• Pharmacology
• Molecular Biology

Background:

• Binge drinking is a risk factor for cardiac arrhythmias, specifically holiday heart syndrome.
• Atrial fibrillation (AF) is the most common arrhythmia associated with holiday heart syndrome.
• Cardiac ryanodine receptor 2 (RyR2) dysfunction and calcium (Ca2+) leak are implicated in alcohol-enhanced AF.

Purpose of the Study:

• To investigate if dantrolene, a RyR2 stabilizer, can prevent AF enhanced by binge alcohol consumption in a rat model.
• To explore the underlying mechanisms involving RyR2 and Ca2+ leak in alcohol-induced AF.

Main Methods:

• A binge drinking rat model was established using alcohol administration.
• Three groups were studied: control, binge alcohol, and binge alcohol with dantrolene treatment.
• Evaluated AF inducibility, AF duration, Ca2+ leak in atrial myocytes, RyR2 phosphorylation, and hemodynamic parameters.

Main Results:

• Binge alcohol consumption significantly increased AF inducibility and duration.
• Dantrolene treatment significantly reduced AF inducibility and duration in binge alcohol rats.
• Binge alcohol increased Ca2+ leak in atrial myocytes, which was attenuated by dantrolene; other measured parameters were not significantly affected.

Conclusions:

• Stabilizing RyR2 with dantrolene effectively prevented binge alcohol-enhanced AF in rats.
• RyR2 stabilization represents a potential therapeutic strategy to mitigate AF arrhythmogenesis caused by binge drinking.