The Role of Epicardial Adipose Tissue Inflammation in Post-Operative Atrial Fibrillation

心房颤动(房颤)是最常见的持续性心律失常，具有显著的相关发病率，包括血栓、中风和心力衰竭的风险以及死亡率的增加。然而，房颤的确切原因在很大程度上仍不清楚。最近的研究表明，循环中的白细胞引起的全身性炎症可能会改变心脏的特性，使其更容易发生房颤的异常电导。令人信服的数据还表明，紧邻心脏周围的脂肪层，即所谓的心外膜脂肪组织(EAT)，在调节健康和疾病的心脏方面发挥着关键作用。推测EAT在健康中的作用包括调节热量、储存能量和对心脏的机械支持。鉴于Eat离心脏很近，它也被认为是调节肥胖对心脏影响的关键环节。因此，研究饮食在疾病状态下如何以及在多大程度上影响心脏组织，已经成为一个强烈的医学兴趣问题。EAT拥有大量的白血球，这些白血球可以产生炎症介质，很容易进入心脏。反过来，这可能会导致有害的后果，如诱发可能引发房颤的异常电脉冲。在这里，我们建议描述在一组接受心脏直视手术的患者中，在EAT-AF级联反应中起作用的白细胞和炎症介质的类型。房颤是心脏手术患者的主要术后并发症，具有特定的额外短期和长期风险，包括中风、死亡和住院时间延长，以及相关的医疗费用增加。因此，减少术后房颤的治疗策略是至关重要的。我们的初步数据表明，在发生术后房颤的患者中，除了炎症标志物的升高外，还有一种特殊类型的白细胞(称为T细胞)升高。在这个项目中，我们验证了在我们的初步分析中确定的T细胞负责这些升高的炎症标志物的产生。这将在那些术后保持正常心律的患者和那些发生房颤的患者身上进行(术后房颤的发生率约为30%-50%)。其次，我们将对一系列炎症标志物进行详细分析，以确定与术后保持正常心律的患者和长期存在的房颤患者相比，术后发生新的房颤的患者的炎症标志物是否增加。在识别和验证不同的特定免疫参数时，我们的目标是调查它们对心脏细胞电特性的个别影响。此外，我们将对心脏组织进行显微镜评估，以寻找进入心脏本身的异常免疫细胞渗透。最后，我们将把这些炎性和电学改变与患者详细的人口统计和病史联系起来。最终，该项目应该成为减少术后房颤发生率的新靶点的基础。

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder with significant associated morbidity including the risk of blood clots, stroke and heart failure alongside an increase in mortality. However, the precise causes of AF remain largely unknown. Recent studies suggest that generalised inflammation caused by circulating white blood cells may have a role in altering the properties of the heart to make it more susceptible to develop the abnormal electrical conduction of AF. Compelling data also shows that the layer of fat immediately surrounding the heart, known as epicardial adipose tissue (EAT), plays a key role in regulating the heart in health and disease. Putative roles of EAT in health include heat regulation, storage of energy and mechanical support to the heart. Given the proximity of EAT to the heart, it is also thought to be a critical link in mediating the effects of obesity on the heart. Hence, it has become a matter of intense medical interest to work out how and to what extent EAT can influence the heart tissue in disease states. EAT hosts a multitude of white blood cells which can produce inflammatory mediators that can easily pass into the heart. In turn, this can result in deleterious consequences such as inducing abnormal electrical impulses that may form the trigger for AF. Here, we propose to characterise the types of white blood cells and inflammatory mediators that play a role in the EAT-AF cascade in a cohort of patients undergoing open heart surgery. AF is the principal post-operative complication in patients undergoing heart surgery and carries specific additional short and long-term risks, including an elevated risk of stroke, death and increased length of hospitalisation with associated heightened health care costs. Hence, treatment strategies to reduce post-operative AF are of paramount importance.Our initial data indicates that a specific type of white blood cells (known as T cells) are elevated in patients who develop post-operative AF in addition to an elevation in markers characteristic of inflammation. In this project, we verify that the T cells identified in our initial analysis are responsible for the production of these elevated inflammatory markers. This will be performed in those patients who remain in normal heart rhythm post-operatively and those who develop AF (post-operative incidence of AF is in the order of 30-50%). Second, we will perform a detailed analysis of a host of inflammation markers to determine if they are increased in patients who develop new post-operative AF compared to patients who remain in normal heart rhythm post-operatively and those with longstanding AF. On identifying and verifying the specific immune parameters that are different we will aim to investigate their individual effect on the electrical properties of heart cells. Moreover, we will microscopically assess the heart tissue to look for abnormal immune cell infiltration into the heart itself. Finally, we will correlate these inflammatory and electrical alterations with detailed demographic and medical histories of patients. Ultimately, the project should form the basis of novel targets to reduce the incidence of post-operative AF.