Sridhar Arun, Nishijima Yoshinori, Terentyev Dmitry, Khan Mahmood, Terentyeva Radmila, Hamlin Robert L, Nakayama Tomohiro, Gyorke Sandor, Cardounel Arturo J, Carnes Cynthia A
Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA.
Cardiovasc Res. 2009 Nov 1;84(2):227-36. doi: 10.1093/cvr/cvp216. Epub 2009 Jun 30.
We sought to define the underlying mechanisms for atrial fibrillation (AF) during chronic heart failure (HF).
Preliminary studies showed that 4 months of HF resulted in irreversible systolic dysfunction (n = 9) and a substrate for sustained inducible AF (>3 months, n = 3). We used a chronic (4-month) canine model of tachypacing-induced HF (n = 10) to assess atrial electrophysiological remodelling, relative to controls (n = 5). Left ventricular fractional shortening was reduced from 37.2 +/- 0.83 to 13.44 +/- 2.63% (P < 0.05). Left atrial (LA) contractility (fractional area change) was reduced from 34.9 +/- 7.9 to 27.9 +/- 4.23% (P < 0.05). Action potential durations (APDs) at 50 and 90% repolarization were shortened by approximately 60 and 40%, respectively, during HF (P < 0.05). HF-induced atrial remodelling included increased fibrosis, increased I(to), and decreased I(K1), I(Kur), and I(Ks) (P < 0.05). HF induced increases in LA Kv channel interacting protein 2 (P < 0.05), no change in Kv4.3, Kv1.5, or Kir2.3, and reduced Kir2.1 (P < 0.05). When I(Ca-L) was elicited by action potential (AP) clamp, HF APs reduced the integral of I(Ca) in control myocytes, with a larger reduction in HF myocytes (P < 0.05). I(CaL) measured with standard voltage clamp was unchanged by HF. Incubation of myocytes with N-acetylcysteine (a glutathione precursor) attenuated HF-induced electrophysiological alterations. LA angiotensin-1 receptor expression was increased in HF.
Chronic HF causes alterations in ion channel expression and ion currents, resulting in attenuation of the APD and atrial contractility and a substrate for persistent AF.
我们试图确定慢性心力衰竭（HF）期间房颤（AF）的潜在机制。
初步研究表明，4个月的HF导致不可逆的收缩功能障碍（n = 9）以及持续性可诱导房颤的基质（>3个月，n = 3）。我们使用慢性（4个月）快速起搏诱导的HF犬模型（n = 10）来评估心房电生理重塑，与对照组（n = 5）相比。左心室缩短分数从37.2±0.83降至13.44±2.63%（P<0.05）。左心房（LA）收缩性（面积变化分数）从34.9±7.9降至27.9±4.23%（P<0.05）。HF期间，复极化50%和90%时的动作电位持续时间（APD）分别缩短约60%和40%（P<0.05）。HF诱导的心房重塑包括纤维化增加、I(to)增加以及I(K1)、I(Kur)和I(Ks)减少（P<0.05）。HF导致LA钾通道相互作用蛋白2增加（P<0.05），Kv4.3、Kv1.5或Kir2.3无变化，Kir2.1减少（P<0.05）。当通过动作电位（AP）钳制引发L型钙电流（I(Ca-L)）时，HF动作电位降低了对照心肌细胞中I(Ca)的积分，HF心肌细胞中的降低幅度更大（P<0.05）。用标准电压钳测量的I(CaL)不受HF影响。用N-乙酰半胱氨酸（一种谷胱甘肽前体）孵育心肌细胞可减轻HF诱导的电生理改变。HF时LA血管紧张素-1受体表达增加。
慢性HF导致离子通道表达和离子电流改变，导致APD和心房收缩性减弱以及持续性AF的基质。
