Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure
Structural and electrical ventricular remodeling in rat acute myocarditis and subsequent heart failure
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DOI：
10.1016/j.cardiores.2004.04.020
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发表时间：
2004-09-01
影响因子：
10.8
通讯作者：
Izumi, T
中科院分区：
文献类型：
--
作者：
Wakisaka, Y;Niwano, S;Izumi, T
目的：我们报道了实验性自身免疫性心肌炎（EAM）大鼠在急性期表现出心室肌动作电位的显著变化和心肌致炎性增强，但其机制尚不清楚。为了探讨急性心肌炎和随后的心力衰竭的心脏重构的机制，生理和分子变化进行了评价沿着EAM的时间过程。方法：用猪心肌肌球蛋白免疫6周龄刘易斯大鼠。在免疫后第14、21、35和60天，组织学、血流动力学和电生理参数（即，观察有效不应期（ERP）、单相动作电位时程（MAPD）和PVC诱导率，并与对照组比较。采用真实的时间定量RT-PCR和Western blot方法检测左心室Kv（+）和L-Ca 2+通道、离子转运蛋白和BNP的表达水平。结果：EAM大鼠在第14天和第21天出现急性心肌炎，伴有大量单个核细胞浸润。随后，在第60天观察到慢性扩张型心肌病（DCM）样结构变化。EAM组的血流动力学参数比对照组差。EAM组ERP和MAPD均较对照组延长，高峰出现在第21天，与PVC诱导时间相平行。Kv4.2、Kv1.5、KChIP 2、frequenin和SERCA 2a的mRNA水平以及Kv4.2和Kv1.5的蛋白水平均降低，尤其是在急性期。结论：Ito相关分子如Kv4.2、1.5、frequenin和KChIP 2表达水平的降低以及MAPD的延长被认为是心室重构的关键机制，并导致EAM在急性炎症期和慢性DCM期的特征性临床表现。(C)2004年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: We reported that experimental autoimmune myocarditis (EAM) rats showed dramatic changes in ventricular action potential and enhanced arrhythmogenicity in the acute phase, but mechanisms for this are still unclear. To investigate the mechanisms of cardiac remodeling in acute myocarditis and subsequent heart failure, physiological and molecular changes were evaluated along the time course of EAM. Methods: Six-week-old Lewis rats were immunized with porcine cardiac myosin. On days 14, 21, 35 and 60 after immunization, histology, hemodynamics and electrophysiological parameters (i.e., effective refractory period (ERP), monophasic action potential duration (MAPD) and PVC inducibility) were evaluated and compared with control rats. After these studies, the expression levels of Kv(+) and L-Ca2+ channels, ion transporters and BNP expressions in the left ventricle were examined by quantitative real time RT-PCR and Western blot analysis. Results: EAM rats showed acute myocarditis with massive infiltration of the mononuclear cells on days 14 and 21. Subsequently, a chronic dilated cardiomyopathy (DCM)-like structural change was observed on day 60. Hemodynamic parameters were worse in EAM than controls. ERP and MAPD were longer in EAM than controls, with a peak on day 21, which was parallel to PVC inducibility. mRNA levels of Kv4.2, Kv1.5, KChIP2, frequenin and SERCA2a, and the protein levels of Kv4.2 and Kv1.5, were reduced, especially in the acute phase. Conclusions: The initial reduction of Ito-related molecules, such as the expression levels of Kv4.2, 1.5, frequenin and KChIP2, and the prolongation of MAPD are considered to be a key mechanism of ventricular remodeling and cause the characteristic clinical findings in EAM in the acute inflammatory phase and chronic DCM phase. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.