Transmural dispersion of repolarization in failing and nonfailing human ventricle.
Transmural dispersion of repolarization in failing and nonfailing human ventricle.
复制标题
DOI：
10.1161/circresaha.109.204891
复制
发表时间：
2010-03-19
影响因子：
20.1
通讯作者：
Efimov IR
中科院分区：
文献类型：
--
作者：
Glukhov AV;Fedorov VV;Lou Q;Ravikumar VK;Kalish PW;Schuessler RB;Moazami N;Efimov IR
在不同的心力衰竭（HF）动物模型中，心室复极离散度在室性心动过速和室颤的发生中起作用。心室肌中层细胞群体内复极的异质性变化被认为是HF表型的重要贡献者。然而，来自人类心脏的电生理数据有限。目的：研究衰竭和非衰竭心脏跨壁复极的电生理重构。我们光学映射动作电位时程（APD）在冠状动脉灌注无疤痕后外侧左心室游离壁楔形准备失败（n=5）和非失败（n=5）的人心脏。在缓慢起搏（S1 S1 = 2, 000 ms）时，在非衰竭心脏中，我们观察到显著的跨壁APD梯度：心外膜下、心肌中层和内膜下APD 80分别为383± 21 ms、455± 20 ms和494± 22 ms。在60%（3/5）的非衰竭心脏中，我们发现与邻近心肌相比，中层心肌细胞岛呈现明显的长APD（537± 40 ms）和陡峭的局部APD梯度（27± 7 ms/mm）。HF导致APD 80延长：内膜下、中层和内膜下分别为477± 22 ms、495± 29 ms和506± 35 ms，而跨壁APD 80差异从111± 13 ms降至29± 6 ms（p<0.005），并存在任何显著的局部APD梯度。在HF中，免疫染色显示心外膜下Cx43表达显著减少。我们提出了第一次直接的实验证据，在人类心脏的跨壁APD梯度。HF导致APD的不均匀延长，从而显著降低跨壁和局部APD梯度。
Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart. To study electrophysiological remodeling of transmural repolarization in the failing and non-failing human hearts. We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and non-failing (n=5) human hearts. During slow pacing (S1S1= 2,000ms), in the non-failing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383±21ms, 455±20ms, and 494±22ms, respectively. In 60% of non-failing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537±40ms) and a steep local APD gradient (27±7ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80: 477±22ms, 495±29ms, and 506±35ms for the subepi-, mid- and subendocardium, respectively, while reducing transmural APD80 difference from 111±13ms to 29±6ms (p<0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of Cx43 expression on the subepicardium. We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.