Martinez-Mateu Laura, Saiz Javier, Aromolaran Ademuyiwa S
Centro de Investigación e Innovación en Bioingeniería, Universitat Politècnica de València, Valencia, Spain.
Cardiac Electrophysiology and Metabolism Research Group, VA New York Harbor Healthcare System, Brooklyn, NY, United States.
Front Physiol. 2019 Sep 25;10:1212. doi: 10.3389/fphys.2019.01212. eCollection 2019.
Obesity mechanisms that make atrial tissue vulnerable to arrhythmia are poorly understood. Voltage-dependent potassium ( , , and ) and L-type calcium currents ( ) are electrically relevant and represent key substrates for modulation in obesity. We investigated whether electrical remodeling produced by high-fat diet (HFD) alone or in concert with acute atrial stimulation were different. Electrophysiology was used to assess atrial electrical function after short-term HFD-feeding in guinea pigs. HFD atria displayed spontaneous beats, increased ( ) and decreased densities. Only with pacing did a reduction in and increased phenotype emerge, leading to a further shortening of action potential duration. Computer modeling studies further indicate that the measured changes in potassium and calcium current densities contribute prominently to shortened atrial action potential duration in human heart. Our data are the first to show that multiple mechanisms (shortened action potential duration, early afterdepolarizations and increased incidence of spontaneous beats) may underlie initiation of supraventricular arrhythmias in obese guinea pig hearts. These results offer different mechanistic insights with implications for obese patients harboring supraventricular arrhythmias.
导致心房组织易发生心律失常的肥胖机制目前仍知之甚少。电压依赖性钾离子通道（ 、 及 ）和L型钙离子通道电流（ ）与电活动密切相关，并且是肥胖状态下调节的关键靶点。我们研究了单纯高脂饮食（HFD）或与急性心房刺激协同作用所引起的电重构是否存在差异。通过电生理学方法评估了豚鼠短期高脂饮食喂养后的心房电功能。高脂饮食组心房出现自发搏动， （ ）密度增加而 密度降低。仅在起搏时才出现 降低及 增加的表型，导致动作电位时程进一步缩短。计算机建模研究进一步表明，所测得的钾离子和钙离子电流密度变化显著促成了人类心脏中心房动作电位时程的缩短。我们的数据首次表明，多种机制（动作电位时程缩短、早期后去极化及自发搏动发生率增加）可能是肥胖豚鼠心脏室上性心律失常发生的基础。这些结果提供了不同的机制见解，对患有室上性心律失常的肥胖患者具有启示意义。
