Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias.The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node.We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats.We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats.

近十年来，代谢综合征（metabolic syndrome）与室上性心律失常的发病率显著升高。代谢综合征是一组以肥胖、高血压、高甘油三酯血症、糖耐量异常及胰岛素抵抗为核心的病理综合征，可增加心房及结性心律失常等多种疾病的发病风险。本研究旨在验证代谢综合征可诱导窦房结（sinoatrial node）电重构并诱发心律失常。我们通过向2月龄雄性Wistar大鼠的饮用水中添加20%蔗糖，成功构建代谢综合征模型。造模8周后，对大鼠进行麻醉并记录心电图（electrocardiogram），结果显示仅模型组大鼠出现心律失常。采用传统微电极及电压钳技术，我们对窦房结的电活动开展了分析。与对照组相比，代谢综合征模型大鼠窦房结内所有细胞的自发放电频率均降低，而仅潜在起搏细胞的舒张期去极化斜率显著升高。相应地，起搏电流If与Ist均出现增强。此外，组织学分析显示，结区心肌细胞周围存在大量脂肪沉积，且交感神经支配水平上升。最后，庞加莱图（Poincaré plot）显示R-R间期与P-P间期存在不规则性，这与代谢综合征模型大鼠窦房结放电电位的变异性记录结果一致。本研究证实，代谢综合征可通过破坏窦房结（SA node）的正常结构与电活动，导致其功能异常，该机制或可解释大鼠心律失常的发生。