延迟的反极化是心脏衰竭和保存的喷射小部分的老鼠中心室节律失常的基础
Jae Hyung Cho1, Rui Zhang1, Peter J Kilfoil1
1Cedars-Sinai Heart Institute, Los Angeles, CA (J.H.C., R.Z., P.J.K., G.d.C., J.I.G., E.M., E.C.).
Circulation
|October 5, 2017
概括
保存喷射分数 (HFpEF) 的心力衰竭增加了由于心脏反极化异常导致的突然死亡风险. 在HFpEF中电流的下调会导致延迟复极化和心室节律失常.
科学领域:
- 心脏病学 心脏病学
- 电子生理学 电子生理学
- 分子生物学分子生物学
背景情况:
- 保存喷射分数 (HFpEF) 的心力衰竭约占所有心力衰竭病例的一半,并且正在上升.
- 突然心脏病死亡是HFpEF患者的主要死亡原因,但其机制尚不清楚.
研究的目的:
- 调查心力衰竭中与保留喷射分数 (HFpEF) 增加对心室节律失常 (VA) 的敏感性背后的机制.
- 探索离子通道功能障碍在与HFpEF相关的突然心脏死亡中的作用.
主要方法:
- 达尔对盐敏感的老鼠被食高盐饮食以诱导HFpEF.
- 心声扫描评估了心脏功能;编程电刺激评估了心律失常的易感性.
- 光学映射,补丁电生理学和分子技术检查了再极化异常和离子通道表达.
主要成果:
- 在HFpEF小鼠中,VA的敏感性显著增加,QT间隔延长,并出现多重重返回回路.
- 观察到短暂的向外电流 (Ito),延迟的整流器电流 (IKr) 和向内整流器电流 (IK1) 的下调.
- 降低I到与降低Kcnd3转录和Kv4.3蛋白水平在HFpEF老鼠心脏相关.
结论:
- 高FpEF显著增加了心室节律失常和心脏突然死亡的风险.
- 由电流下调驱动的异常再极化,是HFpEF中节律失调性增加的基础.
- 这些发现支持了改变电流导致VA和HFpEF突然死亡的假设.
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