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可通过抗炎、抗纤维化和抗氧化机制减少房颤复发的假说来确定炎症、氧化应激、纤维化和心房颤动之间的相互作用。房颤是最常见的严重心律失常--它影响了大约2%的人口，使死亡率翻了一番。房颤的发生率正在增加，治疗只是适度有效。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基础性的作用。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生和复发。炎症标志物，如C-反应蛋白(CRP)和白介素6(IL-6)在房颤患者中升高。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，显著减少了术后心房颤动。鱼油在房颤中发挥益处的机制尚不清楚，也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纤颤类型。因此，在特定目标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将解决这样的假设，即鱼油具有抗炎、抗纤维化和抗氧化作用，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有效性，丰富的科学信息表明它具有抗心律失常的作用，以及其良好的安全性，所有这些都表明，评估其在维持房颤患者窦性心律方面的有效性是当务之急。作为拟议研究基础的机械论方法不仅将为临床疗效问题提供答案，还将提供有关潜在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.