The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Acta Physiol (Oxf). 2013 May;208(1):95-110. doi: 10.1111/apha.12071. Epub 2013 Mar 11.
The remodelling of transmural dispersion of repolarization (TDR) in human heart failure (HF) and in different animal models of cardiac hypertrophy or HF remains a controversial topic. We hypothesize that TDR may exhibit temporal alterations, depending on the stage of the disease.
We systematically investigated the temporal alterations of TDR during the development of cardiac hypertrophy and HF in the mouse pressure-overload model using electrophysiological and molecular biology techniques.
A progressive prolongation of QT interval and changes in the amplitude of the J wave at 2, 5, 9 and 13 weeks were found in anesthetized aorta-banded mice. Action potential duration (APD) at 90% repolarization (APD90) in subendocardial myocytes of the left ventricular free wall remained unchanged at the hypertrophic stage (2 and 5 weeks), but was significantly prolonged in HF mice at 9 and 13 weeks. However, APD90 in subepicardial myocytes exhibited a significant prolongation at 2 weeks and did not progressively extend from 2 weeks to 13 weeks in banded mice. Thus, non-parallel prolongation of APD in subendocardial and subepicardial myocytes led to a reduction in TDR at hypertrophic stage and an amplification of TDR at HF stage. Further experiments revealed that asynchronous down-regulation of voltage-dependent potassium currents (I(to,f), I(K,slow) and I(ss)) and L-type calcium currents (I(Ca-L)) in subendocardial and subepicardial myocytes may contribute to the dynamic remodelling of transmural APD.
The two distinct TDR modes were revealed during the progression of mouse cardiac hypertrophy and failure, indicating that the remodelling of TDR depends on the stage of the disease.
人类心力衰竭（HF）以及不同的心肌肥厚或 HF 动物模型中心肌复极跨壁离散度（TDR）的重塑仍是一个有争议的话题。我们假设 TDR 可能会随着疾病阶段的不同而发生时间上的改变。
我们使用电生理学和分子生物学技术系统地研究了在小鼠压力超负荷模型中心肌肥厚和 HF 发展过程中 TDR 的时间变化。
在麻醉的主动脉结扎小鼠中发现 QT 间期逐渐延长，J 波幅度在 2、5、9 和 13 周时发生变化。左心室游离壁心内膜下心肌的动作电位时程（APD90）在肥厚阶段（2 周和 5 周）保持不变，但在 HF 小鼠中在 9 周和 13 周时明显延长。然而，心外膜下心肌的 APD90 在 2 周时明显延长，并且在结扎小鼠中从 2 周到 13 周没有逐渐延长。因此，心内膜下和心外膜下心肌 APD 的非平行延长导致肥厚阶段 TDR 减少，HF 阶段 TDR 放大。进一步的实验表明，心内膜下和心外膜下心肌中电压依赖性钾电流（I(to,f)、I(K,slow)和 I(ss)）和 L 型钙电流（I(Ca-L)）的异步下调可能导致跨壁 APD 的动态重塑。
在小鼠心肌肥厚和衰竭的进展过程中揭示了两种不同的 TDR 模式，表明 TDR 的重塑取决于疾病的阶段。
