BACKGROUND Alcohol 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 ar-rhythmogenesis.OBJECTIVE The study sought to investigate whether caffeine and binge drinking synergistically affect cardiac arrhythmogen-esis. METHODS A binge drinking rat model (alcohol 2 g/kg, intraperito-neal, 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), nonalcohol, caffeine-only (60 mg/kg, intra-peritoneal) 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 10 mg/kg before each alcohol injection). We also investigated whether alcohol induces Ca(2+ )sparks and dantrolene treatment attenuates alcohol-induced Ca(2+ )leak in ventricular myocytes.RESULTS No arrhythmia was induced with caffeine alone (group C, n = 0 of 8) or alcohol alone (group A, n = 0 of 8). However, alcohol + caffeine induced spontaneous ventricular tachyarrhythmias in all rats (group A+C, n = 8 of 8; P < .001 vs group C or A). Dantrolene prevented ventricular tachyarrhythmia induction in all 7 rats (group A+D, n = 0 of 7; P < .001 vs group A+C). In isolated ventricular myocytes, alcohol significantly increased Ca2+ sparks and dantro-lene treatment reduced alcohol-induced Ca2+ sparks.CONCLUSION Co-consumption of caffeine and binge drinking syn-ergistically promote spontaneous ventricular tachyarrhythmias in rats. Dantrolene treatment can decrease alcohol-enhanced Ca2+ sparks in vitro and prevented alcohol and caffeine induced ventric-ular tachyarrhythmias in vivo.
