Fish Oil for Atrial Fibrillation-Effect and Mechanisms

描述（由申请人提供）：该项目的总体目标是通过解决鱼油通过抗炎、抗纤维化和抗氧化机制减少房颤复发的假设，来确定炎症、氧化应激、纤维化和房颤之间的相互作用。房颤是最常见的严重心律失常，约占人口的2%，死亡率翻倍。房颤的发病率正在增加，治疗效果一般。最近的体外和临床研究表明，炎症在房颤的发病机制中起着重要作用。炎症和由此产生的氧化应激改变了电和结构重构，从而促进了房颤的发作和复发。房颤患者的炎症标志物如c反应蛋白（CRP）和白细胞介素-6 （IL-6）升高。此外，鱼油，一种已知具有抗炎、抗纤维化和抗氧化作用的干预措施，可显著减少术后心房颤动。鱼油对房颤的作用机制尚不清楚，在术后房颤中观察到的有益效果是否延伸到普通人群中更常见的房颤类型也不清楚。因此，在Specific Aim 1中，我们将在一项随机、双盲、安慰剂对照研究中检验补充鱼油降低房颤复发风险的假设。具体目标2将解决鱼油具有抗炎、抗纤维化和抗氧化作用的假设，并通过这些机制降低房颤复发的风险。最近证实的鱼油预防术后房颤的疗效，大量科学资料显示鱼油具有抗心律失常的作用，以及其优异的安全性，都表明评估鱼油在房颤患者维持窦性心律方面的疗效是一个高度优先考虑的问题。机制方法的基础上提出的研究将不仅提供答案的问题，临床疗效，但对潜在的作用机制的基本信息。

DESCRIPTION (provided by applicant): The overall goal of this project is to define the interplay between inflammation, oxidative stress, fibrosis and atrial fibrillation by addressing the hypothesis that fish oil reduces the recurrence of atrial fibrillation, and does so through anti-inflammatory, antifibrotic and antioxidant mechanisms. Atrial fibrillation is the most common serious arrhythmia - it affects approximately 2% of the population and doubles mortality. The incidence of atrial fibrillation is increasing, and treatment is only modestly effective. Recent in vitro and clinical studies suggest that inflammation plays a fundamental role in the pathogenesis of atrial fibrillation. Inflammation, and the resulting oxidative stress, alter electrical and structural remodeling, thus promoting both the onset and recurrence of atrial fibrillation. Markers of inflammation such as C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in patients with atrial fibrillation. Furthermore, fish oil, an intervention known to have anti-inflammatory, antifibrotic and antioxidant effects, markedly reduced postoperative atrial fibrillation. The mechanisms through which fish oil may exert benefits in atrial fibrillation are not known, nor is it known if the beneficial effects observed in postoperative atrial fibrillation extend to the much more common type of fibrillation present in the general population. Accordingly, in Specific Aim 1 we will test the hypothesis that supplementary fish oil reduces the risk of recurrence of atrial fibrillation in a randomized, double-blind, placebo-controlled study. Specific Aim 2 will address the hypothesis that fish oil has anti-inflammatory, anti- fibrotic and antioxidant effects and reduces the risk of recurrence of atrial fibrillation through these mechanisms. The recently demonstrated efficacy of fish oil in the prevention of postoperative atrial fibrillation, the wealth of scientific information showing that it has antiarrhythmic effects, and its excellent safety profile all indicate that the assessment of its efficacy in the maintenance of sinus rhythm in patients with atrial fibrillation is a high priority. The mechanistic approach that underlies the proposed studies will not only provide answers to the question of clinical efficacy, but also fundamental information about potential mechanisms of action.