Electrophysiologic Remodeling of the Left Ventricle in Pressure Overload-Induced Right Ventricular Failure

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• 作者：Maxim Hardziyenka ; MD ; PhD^鈦?/sup> ; ^&dagger ; ; Maria E. Campian ; MD^鈦?/sup> ; Arie O. Verkerk ; PhD^鈦?/sup> ; Sulaiman Surie ; MD^&Dagger ; ; Antoni C.G. van Ginneken ; PhD^鈦?/sup> ; Sara Hakim ; BSc^&sect ; ; Andr&eacute ; C. Linnenbank ; PhD^鈦?/sup> ; H.A.C.M. Rianne de Bruin-Bon ; BSc^鈭?/sup> ; Leander Beekman ; BSc^鈦?/sup> ; Mart N. van der Plas ; MSc^&Dagger ; ; Carol A. Remme ; MD ; PhD^鈦?/sup> ; Toon A.B. van Veen ; PhD^&sect ; ; Paul Bresser ; MD ; PhD^鈦?/sup> ; ^&Dagger ; ; Jacques M.T. de Bakker ; PhD^鈦?/sup> ; ^&dagger ; ; ^&sect ; ; Hanno L. Tan ; MD ; PhD^鈦?/sup> ; ^鈭?/sup> ; ^{h.l.tan@amc.uva.nl}
• 关键词：electrophysiologic remodeling ; pulmonary hypertension ; right ventricular failure
• 刊名：Journal of the American College of Cardiology
• 出版年：2012
• 期刊代码：201_07351097
• 类别：med
• 出版时间：12 June, 2012
• 卷：59
• 期：24
• 页码：2193-2202
• 文件大小：1904 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferencesml version="1.0" encoding="UTF-8"?><h4 class="h4">Objectivesh4>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.<h4 class="h4">Backgroundh4>

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.<h4 class="h4">Methodsh4>

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).<h4 class="h4">Resultsh4>

The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90%repolarization and effective refractory periods (ERPs) (60 卤 1 ms vs. 44 卤 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 卤 2 cm/s vs. 70 卤 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced m>Kcnip2m> expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 卤 0.01 vs. 0.11 卤 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 m>Scn5am> were unaltered. Instead, impulse transmission in RVF was hampered by reduction in cell length (111.6 卤 0.7 渭m vs. 122.0 卤 0.4 渭m; p = 0.02) and width (21.9 卤 0.2 渭m vs. 25.3 卤 0.3 渭m; 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 卤 8 ms vs. 268 卤 5 ms; p = 0.001) and conduction slowing (53 卤 3 cm/s vs. 64 卤 3 cm/s; p = 0.005).<h4 class="h4">Conclusionsh4>

Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.