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

ABSTRACT: Binge drinking is a risk factor for cardiac arrhythmias, known as the holiday heart syndrome. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in this condition. Recent reports indicated that cardiac ryanodine receptor (RyR2) dysfunction and Ca 2+ leak contribute to alcohol-enhanced AF. In this study, we investigated whether stabilizing RyR2 with dantrolene treatment can prevent alcohol-enhanced AF in rats. A binge drinking rat model was established with alcohol (2 g /kg, IP) delivered once every other day for 4 times. The study consisted of following 3 groups: control group (n = 9), binge alcohol group (n = 10), and binge alcohol + dantrolene (A+D) group (dantrolene, 10 mg/kg, IP before each alcohol injection, n = 9). Echocardiography, left ventricular hemodynamics, in vivo atrial electrophysiology and AF inducibility test, RyR2 phosphorylation level, and blood norepinephrine level were studied 24 hours after the last injection. Ca 2+ leak in isolated atrial myocytes from control and binge alcohol rats was examined. Binge alcohol significantly increased AF inducibility (1/9 in control vs. 8/9 in binge alcohol group, P < 0.05) and AF duration. Dantrolene treatment significantly reduced both AF inducibility (2/9 in dantrolene group, P < 0.05) and AF duration. Binge alcohol significantly increased Ca 2+ leak in isolated atrial myocytes, which was reduced by dantrolene treatment. Blood norepinephrine,7 RyR2 phosphorylation level, cardiac echocardiography, and left ventricular hemodynamics were not significantly affected 24 hours after binge drinking. In conclusion, stabilizing RyR2 with dantrolene treatment significantly attenuated binge drinking-enhanced AF, suggesting that therapeutic strategies stabilizing RyR2 could be a preventive measure to blunt binge drinking-enhanced AF arrhythmogenesis.

Novel beta-blocker pretreatment prevents alcohol-induced atrial fibrillation in a rat model.

BACKGROUND: A case report published in 2019 described a patient who presented with difficult-to-manage atrial fibrillation (AF) that consistently was associated with alcohol consumption. After the patient did not respond to drug therapy, a novel beta-blocker (BB) pretreatment regimen initiated immediately before alcohol consumption successfully prevented AF occurrence. OBJECTIVE: The purpose of this study was to test the hypothesis that a novel prophylactic BB therapy given before alcohol consumption could prevent AF in a rat model. METHODS: An alcohol-induced AF model was developed in adult Sprague-Dawley rats of both sexes by administering alcohol (2 g/kg intraperitoneal [IP]) once every other day for a total of 4 times. Three groups were enrolled: alcohol (EtOH; n = 10); alcohol plus BB (metoprolol 50 mg/kg IP) pretreatment (EtOH+BB; n = 10); and control (n = 9). Cardiac function (assessed by echocardiography and left ventricular hemodynamics) and in vivo atrial electrophysiology and AF inducibility tests were performed 24 hours after the last injection. RESULTS: All but 1 rat completed the study. Alcohol exposure did not significantly impact cardiac function and the atrial effective refractory period. However, alcohol exposure significantly increased AF inducibility [median (first and third quartile [Q1-Q3]) 0% (0%-0%) in control vs 60% (25%-100%) in the EtOH group; P <.05] and AF duration [0 second (0-0 second) in control vs 0.81 second (0.24-3.67 seconds) in the EtOH group; P <.05]. Compared to the EtOH group, the EtOH+BB group had significantly reduced AF inducibility [0% (0%-22.5%); P <.05] and duration [0 second (0-0.2 second); P <.05]. CONCLUSION: Metoprolol pretreatment before alcohol administration significantly decreased AF induction in rats. These findings suggest that BB pretreatment is a promising prophylaxis regimen for alcohol-induced AF.