Mechanisms of cardiac ethanol toxicity and novel treatment options

Ethanol can acutely and chronically alter cardiomyocyte and whole-organ function in the heart. Importantly, ethanol acutely and chronically predisposes to arrhythmias, while chronic abuse can induce heart failure. However, the molecular mechanisms of ethanol toxicity in the heart are incompletely understood. In this review, we summarize the current mechanistic knowledge on cardiac ethanol toxicity, with a focus on druggable pathways. Ethanol effects on excitation-contraction coupling, oxidative stress, apoptosis, and cardiac metabolism, as well as effects of ethanol metabolites will be discussed. Important recent findings have been gained by investigation of acute ethanol effects. These include a renewed focus on reactive oxygen species (ROS) and induction of SR Ca2+ leak by CaMKII-mediated pathways downstream of ROS. Furthermore, a clinical outlook into potential novel treatment options is provided. (C) 2018 Elsevier Inc. All rights reserved.