Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.
J Am Coll Cardiol. 2012 Jun 12;59(24):2193-202. doi: 10.1016/j.jacc.2012.01.063.
The purpose of this study was to analyze the electrophysiologic remodeling of the atrophic left ventricle (LV) in right ventricular (RV) failure (RVF) after RV pressure overload.
The LV in pressure-induced RVF develops dysfunction, reduction in mass, and altered gene expression, due to atrophic remodeling. LV atrophy is associated with electrophysiologic remodeling.
We conducted epicardial mapping in Langendorff-perfused hearts, patch-clamp studies, gene expression studies, and protein level studies of the LV in rats with pressure-induced RVF (monocrotaline [MCT] injection, n = 25; controls with saline injection, n = 18). We also performed epicardial mapping of the LV in patients with RVF after chronic thromboembolic pulmonary hypertension (CTEPH) (RVF, n = 10; no RVF, n = 16).
The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90% repolarization and effective refractory periods (ERPs) (60 ± 1 ms vs. 44 ± 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 ± 2 cm/s vs. 70 ± 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 ± 0.01 vs. 0.11 ± 0.02; p < 0.05). Conduction slowing was not explained by impaired impulse formation, as AP maximum upstroke velocity, whole-cell sodium current magnitude/properties, and mRNA levels of Scn5a were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 ± 0.7 μm vs. 122.0 ± 0.4 μm; p = 0.02) and width (21.9 ± 0.2 μm vs. 25.3 ± 0.3 μm; p = 0.002), and impaired cell-to-cell impulse transmission (24% reduction in Connexin-43 levels). The LV of patients with CTEPH with RVF also exhibited ERP prolongation (306 ± 8 ms vs. 268 ± 5 ms; p = 0.001) and conduction slowing (53 ± 3 cm/s vs. 64 ± 3 cm/s; p = 0.005).
Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.
本研究旨在分析右心室（RV）压力超负荷后萎缩左心室（LV）的电生理重构。
压力诱导的 RVF 中的 LV 由于萎缩性重塑而出现功能障碍、质量减少和基因表达改变。LV 萎缩与电生理重构有关。
我们在 Langendorff 灌注心脏中进行心外膜映射、膜片钳研究、LV 基因表达研究和蛋白水平研究，研究对象为接受单克隆抗体（MCT）注射的压力诱导 RVF 大鼠（n = 25；接受生理盐水注射的对照大鼠，n = 18）。我们还对慢性血栓栓塞性肺动脉高压（CTEPH）后 RVF 患者的 LV 进行心外膜映射（RVF，n = 10；无 RVF，n = 16）。
MCT 诱导的 RVF 大鼠的 LV 表现出电生理重构：90%复极时动作电位（APs）和有效不应期（ERPs）更长（60 ± 1 ms 比 44 ± 1 ms；p < 0.001），纵向传导速度更慢（62 ± 2 cm/s 比 70 ± 1 cm/s；p = 0.003）。AP/ERP 延长与 Kcnip2 表达减少一致，Kcnip2 编码复极化钾通道亚基 KChIP2（0.07 ± 0.01 比 0.11 ± 0.02；p < 0.05）。AP 最大上升速度、全细胞钠电流幅度/特性和 Scn5a 的 mRNA 水平未改变，表明冲动形成不受损害，因此，AP/ERP 延长不能用冲动形成受损来解释。相反，RVF 中的冲动传递受到细胞长度减小（111.6 ± 0.7 μm 比 122.0 ± 0.4 μm；p = 0.02）和宽度减小（21.9 ± 0.2 μm 比 25.3 ± 0.3 μm；p = 0.002）以及冲动细胞间传递受损（Connexin-43 水平降低 24%）的阻碍。CTEPH 合并 RVF 患者的 LV 也表现出 ERP 延长（306 ± 8 ms 比 268 ± 5 ms；p = 0.001）和传导减慢（53 ± 3 cm/s 比 64 ± 3 cm/s；p = 0.005）。
压力诱导的 RVF 与萎缩 LV 的电生理重构有关。
