Published Online
on September 24, 2009

A more recent version of this article appeared on November 1, 2009

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Original Article

Development of Left Ventricular Diastolic Dysfunction with Preservation of Ejection Fraction during Progression of Infant Right Ventricular Hypertrophy

Kazuo Kitahori; Huamei He; Mitsuhiro Kawata; Douglas B. Cowan; Ingeborg Friehs; Pedro J. del Nido and Francis X. McGowan, Jr.¹

Children's Hospital Boston, Harvard Medical School, Boston, MA

^* Corresponding author; email: francis.mcgowan{at}childrens.harvard.edu

Background—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).

Methods and Results—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).

Conclusion—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.

Key Words: apoptosis • diastole • heart failure • hypertrophy • right ventricle