Eble D M, Spinale F G
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Am J Physiol. 1995 Jun;268(6 Pt 2):H2426-39. doi: 10.1152/ajpheart.1995.268.6.H2426.
Chronic supraventricular tachycardia (SVT)-induced cardiomyopathy is associated with left ventricular (LV) dilatation, increased wall stress, neurohormonal activation, and no change in LV mass. To determine mechanisms for changes in LV geometry and function with SVT cardiomyopathy, LV and myocyte function, contractile protein content and mRNA levels, and cytoskeletal protein structure and mRNA levels were examined in 12 pigs with SVT cardiomyopathy (paced at 240 beats/min for 3 wk) and in 12 controls. With SVT cardiomyopathy, LV fractional shortening fell by 61%, and end-diastolic dimension increased by 42%, with no change in LV mass-to-body weight ratio (3.36 +/- 0.15 vs. 3.14 +/- 0.13 g/kg). Myocyte contractile function was reduced by 33%, myocyte length was increased by 28%, and cross-sectional area was decreased by 19% with SVT cardiomyopathy. Total protein, myosin heavy chain (MHC), and actin appeared unchanged with SVT cardiomyopathy at the LV or myocyte level. Moreover, there was no change in mRNA levels for MHC (0.57 +/- 0.05 vs. 0.59 +/- 0.09 mRNAOD/rRNAOD) or cardiac alpha-actin (0.58 +/- 0.08 vs. 0.58 +/- 0.04 mRNAOD/rRNAOD) with SVT cardiomyopathy. In contrast, mRNA levels for specific cytoskeletal proteins were significantly increased with SVT cardiomyopathy, and immunofluorescent localization of contractile and cytoskeletal proteins in isolated myocytes revealed alterations in cytoskeletal architecture. Thus changes in LV and myocyte geometry with SVT cardiomyopathy were associated with no change in contractile protein content or mRNA at the chamber or myocyte level. Furthermore, increased cytoskeletal protein abundance and mRNA and reorientation of cardiocyte cytoarchitecture may have contributed to the LV and myocyte remodeling with SVT cardiomyopathy.
慢性室上性心动过速（SVT）诱发的心肌病与左心室（LV）扩张、壁应力增加、神经激素激活以及左心室质量无变化有关。为了确定SVT心肌病时左心室几何形状和功能改变的机制，对12只患有SVT心肌病（以240次/分钟的频率起搏3周）的猪和12只对照猪进行了左心室和心肌细胞功能、收缩蛋白含量和mRNA水平以及细胞骨架蛋白结构和mRNA水平的检测。患有SVT心肌病时，左心室缩短分数下降了61%，舒张末期内径增加了42%，而左心室质量与体重比无变化（3.36±0.15 vs. 3.14±0.13 g/kg）。SVT心肌病时，心肌细胞收缩功能降低了33%，心肌细胞长度增加了28%，横截面积减少了19%。在左心室或心肌细胞水平，总蛋白、肌球蛋白重链（MHC）和肌动蛋白在SVT心肌病时似乎没有变化。此外，SVT心肌病时MHC的mRNA水平（0.57±0.05 vs. 0.59±0.09 mRNAOD/rRNAOD）或心脏α-肌动蛋白的mRNA水平（0.58±0.08 vs. 0.58±0.04 mRNAOD/rRNAOD）没有变化。相比之下，SVT心肌病时特定细胞骨架蛋白的mRNA水平显著增加，分离的心肌细胞中收缩蛋白和细胞骨架蛋白的免疫荧光定位显示细胞骨架结构发生了改变。因此，SVT心肌病时左心室和心肌细胞几何形状的改变与心室或心肌细胞水平收缩蛋白含量或mRNA的变化无关。此外，细胞骨架蛋白丰度和mRNA的增加以及心肌细胞细胞结构的重新定向可能促成了SVT心肌病时左心室和心肌细胞的重塑。
