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

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• 作者：Maxim Hardziyenka ; MD ; PhD^?/sup> ; ^&dagger ; ; Maria E. Campian ; MD^?/sup> ; Arie O. Verkerk ; PhD^?/sup> ; Sulaiman Surie ; MD^&Dagger ; ; Antoni C.G. van Ginneken ; PhD^?/sup> ; Sara Hakim ; BSc^&sect ; ; Andr&eacute ; C. Linnenbank ; PhD^?/sup> ; H.A.C.M. Rianne de Bruin-Bon ; BSc^?/sup> ; Leander Beekman ; BSc^?/sup> ; Mart N. van der Plas ; MSc^&Dagger ; ; Carol A. Remme ; MD ; PhD^?/sup> ; Toon A.B. van Veen ; PhD^&sect ; ; Paul Bresser ; MD ; PhD^?/sup> ; ^&Dagger ; ; Jacques M.T. de Bakker ; PhD^?/sup> ; ^&dagger ; ; ^&sect ; ; Hanno L. Tan ; MD ; PhD^?/sup> ; ^?/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
• 出版时间：12 June, 2012
• 年：2012
• 卷：59
• 期：24
• 页码：2193-2202
• 全文大小：1904 K

文摘

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class=""h4"">Objectives

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.

class=""h4"">Background

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.

class=""h4"">Methods

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).

class=""h4"">Results

The LV of rats with MCT-induced RVF exhibited electrophysiologic remodeling: longer action potentials (APs) at 90 % repolarization and effective refractory periods (ERPs) (60 ¡À 1 ms vs. 44 ¡À 1 ms; p < 0.001), and slower longitudinal conduction velocity (62 ¡À 2 cm/s vs. 70 ¡À 1 cm/s; p = 0.003). AP/ERP prolongation agreed with reduced Kcnip2 expression, which encodes the repolarizing potassium channel subunit KChIP2 (0.07 ¡À 0.01 vs. 0.11 ¡À 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 ¡À 0.7 ¦Ìm vs. 122.0 ¡À 0.4 ¦Ìm; p = 0.02) and width (21.9 ¡À 0.2 ¦Ìm vs. 25.3 ¡À 0.3 ¦Ìm; 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 ¡À 8 ms vs. 268 ¡À 5 ms; p = 0.001) and conduction slowing (53 ¡À 3 cm/s vs. 64 ¡À 3 cm/s; p = 0.005).

class=""h4"">Conclusions

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