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酒精和咖啡因协同诱发自发性室性心律失常:丹曲林治疗可改善。

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

作者信息

Zhang Youhua, Kim Christopher, Wasif Nawal, Li Ying, Huang Yuan, Kobayashi Satoru, Udo-Bellner Lars, Stout Randy, Ojamaa Kaie

机构信息

Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York.

出版信息

Heart Rhythm O2. 2023 Jul 20;4(9):549-555. doi: 10.1016/j.hroo.2023.07.005. eCollection 2023 Sep.

Abstract

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 arrhythmogenesis.

OBJECTIVE

The study sought to investigate whether caffeine and binge drinking synergistically affect cardiac arrhythmogenesis.

METHODS

A binge drinking rat model (alcohol 2 g/kg, intraperitoneal, 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, intraperitoneal) 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 sparks and dantrolene treatment attenuates alcohol-induced Ca 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; < .001 vs group C or A). Dantrolene prevented ventricular tachyarrhythmia induction in all 7 rats (group A+D, n = 0 of 7; < .001 vs group A+C). In isolated ventricular myocytes, alcohol significantly increased Ca sparks and dantrolene treatment reduced alcohol-induced Ca sparks.

CONCLUSION

Co-consumption of caffeine and binge drinking synergistically promote spontaneous ventricular tachyarrhythmias in rats. Dantrolene treatment can decrease alcohol-enhanced Ca sparks in vitro and prevented alcohol and caffeine induced ventricular tachyarrhythmias in vivo.

摘要

背景

酒精和咖啡因是普通人群中两种常见的消费物质,且这两种物质经常同时被摄入。这两种物质都可能增加心律失常的风险。然而,酒精和咖啡因同时摄入是否会协同增强心律失常的发生尚不清楚。

目的

本研究旨在探讨咖啡因和暴饮酒精是否会协同影响心律失常的发生。

方法

采用暴饮酒精大鼠模型(酒精2 g/kg,腹腔注射,隔天一次,共3次)。将4月龄大鼠(雌雄不限)随机分为以下4组:单纯暴饮酒精组(A组)(n = 8)、不饮酒仅给予咖啡因组(C组)(60 mg/kg,腹腔注射)(n = 8)、暴饮酒精加咖啡因组(A+C组)(n = 8)以及暴饮酒精+咖啡因+丹曲林组(A+D组)(n = 7,每次酒精注射前给予丹曲林10 mg/kg)。我们还研究了酒精是否会诱导钙火花以及丹曲林治疗是否会减轻酒精诱导的心室肌细胞钙泄漏。

结果

单独使用咖啡因(C组,8只大鼠中0只发生心律失常)或单独使用酒精(A组,8只大鼠中0只发生心律失常)均未诱发心律失常。然而,酒精+咖啡因在所有大鼠中诱发了自发性室性快速心律失常(A+C组,8只大鼠中8只发生;与C组或A组相比,P <.001)。丹曲林可预防所有7只大鼠发生室性快速心律失常(A+D组,7只大鼠中0只发生;与A+C组相比,P <.001)。在分离的心室肌细胞中,酒精显著增加钙火花,而丹曲林治疗可减少酒精诱导的钙火花。

结论

咖啡因与暴饮酒精同时摄入可协同促进大鼠自发性室性快速心律失常的发生。丹曲林治疗可在体外减少酒精增强的钙火花,并在体内预防酒精和咖啡因诱导的室性快速心律失常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c1c/10513921/5f979018f131/gr1.jpg

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