Department of Medicine, MacKay Medical College, New Taipei City, Taiwan; Division of Cardiology, Department of Internal Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan.
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
J Mol Cell Cardiol. 2018 Jan;114:150-160. doi: 10.1016/j.yjmcc.2017.10.011. Epub 2017 Oct 31.
Chronic, excessive ethanol intake has been linked with various electrical instabilities, conduction disturbances, and even sudden cardiac death, but the underlying cause for the latter is insufficiently delineated.
We studied surface electrocardiography (ECG) in a community-dwelling cohort with moderate-to-heavy daily alcohol intake (grouped as >90g/day, ≤90g/day, and nonintake).
Compared with nonintake, heavier alcohol users showed markedly widened QRS duration and higher prevalence of QRS fragmentation (64.3%, 50.9%, and 33.7%, respectively, χ 12.0, both p<0.05) on surface ECG across the 3 groups. These findings were successfully recapitulated in 14-week-old C57BL/6 mice that were chronically given a 4% or 6% alcohol diet and showed dose-related slower action potential upstroke, reduced resting membrane potential, and disorganized or decreased intraventricular conduction (all p<0.05). Immunodetection further revealed increased ventricular collagen I depots with Cx43 downregulation and remodeling, together with clustered and diminished membrane Nav1.5 distribution. Administration of Cx43 blocker (heptanol) and Nav1.5 inhibitor (tetrodotoxin) in the mice each attenuated the suppression ventricular conduction compared with nonintake mice (p<0.05).
Chronic excessive alcohol ingestion is associated with dose-related phenotypic intraventricular conduction disturbances and QRS fragmentation that can be recapitulated in mice. The mechanisms may involve suppressed gap junction and sodium channel functions, together with enhanced cardiac fibrosis that may contribute to arrhythmogenesis.
慢性、过量饮酒与多种电不稳定性、传导障碍甚至突发性心脏死亡有关，但后者的根本原因尚不清楚。
我们研究了社区居住的中重度每日饮酒人群（分为>90g/天、≤90g/天和不饮酒）的体表心电图（ECG）。
与不饮酒者相比，较重的饮酒者在三组体表心电图上表现出明显增宽的 QRS 持续时间和更高的 QRS 碎裂发生率（分别为 64.3%、50.9%和 33.7%，χ 12.0，均 p<0.05）。这些发现成功地在 14 周龄慢性给予 4%或 6%酒精饮食的 C57BL/6 小鼠中重现，表现为动作电位上升速度减慢、静息膜电位降低、室内传导紊乱或减少（均 p<0.05）。免疫检测进一步显示心室胶原 I 沉积增加，Cx43 下调和重构，以及膜 Nav1.5 分布聚集和减少。与不饮酒小鼠相比，给予 Cx43 阻断剂（庚醇）和 Nav1.5 抑制剂（河豚毒素）均可减轻小鼠心室传导的抑制（p<0.05）。
慢性过量饮酒与剂量相关的表型室内传导障碍和 QRS 碎裂有关，可在小鼠中重现。其机制可能涉及间隙连接和钠通道功能抑制，以及增强的心脏纤维化，可能导致心律失常发生。
