Development of left ventricular diastolic dysfunction with preservation of ejection fraction during progression of infant right ventricular hypertrophy.
Development of left ventricular diastolic dysfunction with preservation of ejection fraction during progression of infant right ventricular hypertrophy.
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DOI：
10.1161/circheartfailure.109.862664
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
McGowan FX Jr
中科院分区：
文献类型：
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作者：
Kitahori K;He H;Kawata M;Cowan DB;Friehs I;Del Nido PJ;McGowan FX Jr
进行性左室（LV）功能障碍可能是慢性右心室（RV）压力过载（如法洛四联症）患者的主要晚期并发症。因此，我们在婴儿压力负荷型左室肥厚（RVH）模型中检查左室功能（连续超声心动图和离体Langendorff）和组织学。在PAB术后2-8周处死接受肺动脉绑扎术（PAB）的10日龄家兔（每个时间点N=6只，总数= 48只），并与年龄匹配的假对照组进行比较。尽管左室射血分数（EF）保持不变，但左室性能（心肌性能指数，MPI）随着RVH的进展而下降。此外，RVH引起明显的室间隔位移，室间隔收缩性降低，左室收缩期末（LVDs）和舒张期（LVDd）尺寸降低，导致左室舒张功能障碍，表现为EF保留。PAB组在6-8周后出现了明显的室间隔和左室游离壁凋亡（肌细胞特异性TUNEL和活化的caspase-3）、纤维化（马松三色染色）和毛细血管密度降低（CD31免疫染色）（均p<0.05）。这是第一个表明右室压力过载导致RVH导致左室舒张功能障碍的研究，同时通过对隔膜和左室心肌的机械和分子作用保持EF。特别是，RVH的发展与室间隔和左室细胞凋亡以及左室毛细血管密度降低有关。
Progressive left ventricular (LV) dysfunction can be a major late complication in patients with chronic right ventricular (RV) pressure overload (e.g., tetralogy of Fallot). We therefore examined LV function (serial echocardiography and ex vivo Langendorff) and histology in a model of infant pressure-load RV hypertrophy (RVH). Ten-day-old rabbits (N=6 per time point, total = 48) that underwent pulmonary artery banding (PAB) were sacrificed at 2–8 weeks after PAB, and comparisons were made with age-matched sham controls. LV performance (myocardial performance index, MPI) decreased during the progression of RVH although the LV ejection fraction (EF) was maintained. In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic (LVDs) and diastolic (LVDd) dimensions, resulting in LV diastolic dysfunction with the appearance of preserved EF. Significant septal and LV free wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson’s trichrome stain), and reduced capillary density (CD31 immunostaining) occurred in the PAB group after 6–8 wks (all p<0.05). This is the first study showing that pressure overload of the RV resulting in RVH causes LV diastolic dysfunction while preserving EF through mechanical and molecular effects upon the septum and LV myocardium. In particular, the development of RVH is associated with septal and LV apoptosis and reduced LV capillary density.