Alcohol and caffeine synergistically induce spontaneous ventricular tachyarrhythmias: ameliorated with dantrolene treatment

BackgroundAlcohol and caffeine are the 2 frequently consumed substances in the general population and the 2 substances are frequently co-consumed. Both substances may increase cardiac arrhythmia risk. However, it is unknown whether alcohol and caffeine co-consumption can synergistically enhance cardiac arrhythmogenesis.ObjectiveTo investigate whether caffeine and binge drinking synergistically affect cardiac arrhythmogenesis.MethodsA binge drinking rat model (alcohol 2g/kg, IP, every other day for 3 times) was used. Rats (4 months old, both sexes) were randomized into the following 4 groups: Binge alcohol only group (A, n=8), Non-alcohol, caffeine (60mg/kg, IP) only group (C, n=8), Binge alcohol plus caffeine group (A+C, n=8), and Binge alcohol + caffeine + dantrolene group (A+D, n=7, treated with dantrolene 10mg/kg before each alcohol injection). We also investigated whether alcohol induces Ca2+ sparks and dantrolene treatment attenuates alcohol-induced Ca2+ leak in ventricular myocytes.ResultsNo arrhythmia was induced with caffeine alone (group C, 0/8) or alcohol alone (group A, 0/8). However, alcohol + caffeine induced spontaneous ventricular tachyarrhythmias in all rats (group A+C, 8/8, P<0.001 versus group C or A). Dantrolene prevented ventricular tachyarrhythmia induction in all 7 rats (group A+D, 0/7, P<0.001 versus Group A+C). In isolated ventricular myocytes, alcohol significantly increased Ca2+ sparks and dantrolene treatment reduced alcohol-induced Ca2+ sparks.ConclusionCo-consumption of caffeine and binge drinking synergistically promote spontaneous ventricular tachyarrhythmias in rats. Dantrolene treatment can decrease alcohol enhanced Ca2+ sparks in vitro and prevented alcohol and caffeine induced ventricular tachyarrhythmias in vivo.