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Electrophysiologic remodeling of the left ventricle in pressure overload-induced right ventricular failure.

Abstract：

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. 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. 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). 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 ± 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). CONCLUSIONS:Pressure-induced RVF is associated with electrophysiologic remodeling of the atrophic LV.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Hardziyenka M,Campian ME,Verkerk AO,Surie S,van Ginneken AC,Hakim S,Linnenbank AC,de Bruin-Bon HA,Beekman L,van der Plas MN,Remme CA,van Veen TA,Bresser P,de Bakker JM,Tan HL

doi

10.1016/j.jacc.2012.01.063

subject

Has Abstract

pub_date

2012-06-12 00:00:00

pages

2193-202

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(12)01191-6

journal_volume

pub_type

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Electrophysiologic remodeling of the left ventricle in pressure overload-induced right ventricular failure.