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有更多的人。目前，近五分之一的人目前患有肥胖症；在英国，大约30%的成年人患有肥胖症，在美国，这一比例超过40%。肥胖直接导致心血管危险因素、心血管疾病的发展和心血管疾病死亡。这与其他心血管危险因素无关。有强有力的证据表明，肥胖和随之而来的代谢功能障碍、炎症和脂肪组织沉积导致了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在肥胖环境中是否有效。在本课程中，我们将1)研究肥胖如何改变房电特性，以及这些变化是否会导致房性心律失常；2)研究当前和新的心血管疗法对肥胖房颤患者以及动物和细胞模型的有效性。实验将在小鼠全心、人类诱导多能干细胞来源的心肌细胞和脂肪细胞的共同培养以及患者临床解剖标测数据集上进行。我们将使用人工智能技术来询问心脏电生理改变。这些研究将对肥胖和心脏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.