Department of Internal Medicine II, University Medical Center Regensburg, Germany.
Department of Internal Medicine II, University Medical Center Regensburg, Germany.
Pharmacol Ther. 2019 May;197:1-10. doi: 10.1016/j.pharmthera.2018.12.006. Epub 2018 Dec 14.
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 Ca leak by CaMKII-mediated pathways downstream of ROS. Furthermore, a clinical outlook into potential novel treatment options is provided.
乙醇可在急性和慢性阶段改变心肌细胞和心脏整体的功能。重要的是，乙醇可在急性和慢性阶段诱发心律失常，而慢性滥用则可导致心力衰竭。然而，乙醇在心脏中的毒性的分子机制尚不完全清楚。在本综述中，我们总结了目前关于心脏乙醇毒性的机制知识，重点是可药物干预的途径。我们将讨论乙醇对兴奋-收缩偶联、氧化应激、细胞凋亡和心脏代谢的影响，以及乙醇代谢物的作用。通过对急性乙醇作用的研究，我们获得了一些重要的新发现。这些发现包括对活性氧（ROS）的重新关注，以及 ROS 下游的 CaMKII 介导途径引起的肌浆网 Ca 泄漏。此外，我们还对潜在的新型治疗选择提供了临床展望。
