Obesity and Cardiac Arrhythmias - Identifying Effective Anti-Arrhythmic Therapies in Obesity.

人类的总重量正在上升，这不仅仅是因为我们的人数增加了。目前，全球近五分之一的人肥胖；在英国，大约30%的成年人肥胖，而在美国，这一比例超过了40%。肥胖直接影响心血管危险因素的发生、心血管疾病的发展和心血管疾病的死亡率。这与其他心血管危险因素无关。有强有力的证据表明，肥胖及其导致的代谢功能障碍、炎症和脂肪组织沉积会增加心房心律失常的风险。然而，目前尚不清楚标准或新型抗心律失常药物对肥胖是否有效。在这项研究中，我们将1)研究肥胖如何改变心房电特性以及这些特性是否导致心房心律失常，2)研究当前和新型心血管治疗方法在肥胖心房颤动患者以及动物和细胞模型中的有效性。实验将在小鼠全心、人类诱导的多能干细胞衍生的心肌细胞和脂肪细胞的共培养以及患者临床电解剖图谱数据集中进行。我们将采用人工智能技术来询问心脏电生理变化。这些研究将对肥胖和心房电功能产生新的见解，并确定最佳的治疗干预措施。

The total weight of humanity is rising, and not just because there are more of us. Currently, nearlyone-fifth of all humans are currently obese; in UK around 30% of adults are obese and in the UnitedStates this proportion exceeds 40%. Obesity contributes directly to incident cardiovascular riskfactors, development of cardiovascular disease and cardiovascular disease mortality. This isindependent of other cardiovascular risk factors. There is strong evidence that obesity andconsequent metabolic dysfunction, inflammation and adipose tissue deposition contributes toarrhythmic risk in atria. However, it is not known whether standard or novel anti-arrhythmic drugs areeffective in the setting of obesity. In this studentship we will 1) examine how obesity alters atrialelectrical properties and whether these lead to atrial arrhythmias, 2) investigate the effectiveness ofcurrent and novel cardiovascular therapeutics in obese patients with atrial fibrillation and animal andcellular models. Experiments will be carried out in mouse whole hearts, co-cultures of humaninduced pluripotent stem cell-derived cardiomyocytes and adipocytes and patient clinicalelectroanatomical mapping datasets. We will employ artificial intelligence techniques to interrogatecardiac electrophysiological alterations. These studies will generate new insights into obesity andatrial electrical function and identify optimal therapeutic interventions.