Ancillary: Inflammation/Oxidation, Omega-3's, & Post-Op AFiB & Cognitive Decline

描述(由申请人提供)： 摘要欧米茄-3脂肪酸预防术后心房颤动试验(OPERA)是一项资助、双盲、安慰剂对照、多中心、随机临床试验，检验围手术期鱼油可减少1516例心脏手术(CS)患者术后心房颤动或扑动(AF)的发生。在这项辅助研究中，我们将增加对CS第二个主要并发症的评估，即术后认知功能下降的评估，并评估关键的循环和组织生物标记物，以研究手术后认知功能下降和房颤可能发生的关键新机制，并验证鱼油通过防止氧化应激和随后的炎症而减少术后房颤和可能的认知功能下降的假说。作为一项嵌套的辅助研究，这提供了一个高成本和高时间效率的机会，对高度相关的生物通路进行创新研究，以及潜在的治疗术后房颤和认知功能下降的新方法，这是CS最常见的两种并发症。这些发现将为氧化和炎症途径如何介导术后认知功能下降和房颤的发病机制提供迄今为止最全面的评估，并直接测试低成本、低风险的膳食补充剂是否影响局部和系统对CS的反应或改变术后认知损伤的风险。这些结果将导致未来与这些科学问题相关的创新研究目标和假设的爆炸性增长，以及将CS的侮辱降至最低的新药或其他技术的新目标。同时，我们能够在大型对照试验中直接确定围手术期鱼油对CS相关的氧化应激、炎症和认知功能下降的影响，这将刺激未来令人兴奋的研究，如果成功，还将直接改善医疗保健服务的实践。公共卫生相关性：项目描述虽然心脏手术后房颤和认知能力下降是非常常见的不良后果，但这些并发症的病理生理学和潜在有效的治疗方法都没有得到很好的理解。该项目将是第一个通过统一的方法解决心脏手术中这两个最常见的并发症的项目，可以产生长期的增长和一种新的跨学科调查类型的进展，对未来的研究和临床患者护理都具有巨大的影响。(摘要结束)

DESCRIPTION (provided by applicant): Abstract The Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial is a funded, double-blind, placebo-controlled, multicenter, randomized clinical trial testing the hypothesis that peri-op fish oil will reduce occurrence of post-op atrial fibrillation or flutter (AF) in 1516 patients undergoing cardiac surgery (CS). In this Ancillary Study, we will add the evaluation of a second major CS complication to the study, that of post-op cognitive decline, and assess key circulating and tissue biomarkers to investigate key novel mechanistic pathways whereby post-op cognitive decline and AF may each occur and also test the hypothesis that fish oil decreases post-op AF and possibly cognitive decline by preventing oxidative stress and subsequent inflammation. As a nested Ancillary Study, this provides a highly cost- and time- efficient opportunity to perform innovative investigations on highly relevant biologic pathways as well as potential novel treatments for post-op AF and cognitive decline, the two most common complications of CS. These findings will provide the most comprehensive evaluation to-date of how oxidative and inflammatory pathways mediate pathogenesis of post-op cognitive decline and AF, and directly test whether a low cost, low risk dietary supplement affects local and systematic responses to CS or alters risk of post-op cognitive injury. The results will lead to an explosion of future innovative research aims and hypotheses linked to these scientific issues as well as novel targets for new drugs or other technologies to minimize the insults from CS. At the same time, our ability to directly determine in a large controlled trial the effects of peri-op fish oil on CS-related oxidative stress, inflammation, and cognitive decline will stimulate exciting future research but also, if successful, directly improve practice of health care delivery. PUBLIC HEALTH RELEVANCE: Project Narrative Although post-operative atrial fibrillation and cognitive decline are extremely common adverse outcomes following cardiac surgery, neither the pathophysiology of nor potentially effective treatments for these complications are well-understood This project will be the first of its kind to address these two most common complications of cardiac surgery through a unified approach that could yield long-term growth and advances in a new genre of interdisciplinary inquiry, with tremendous implications for both future research and clinical patient care. (End of Abstract)