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Original Articles

Development of Left Ventricular Diastolic Dysfunction With Preservation of Ejection Fraction During Progression of Infant Right Ventricular Hypertrophy

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

From the Departments of Cardiovascular Surgery (I.F., P.J.N., K.K., M.K.) and Anesthesiology, Perioperative and Pain Medicine (H.H., D.B.C., F.X.M.), Children’s Hospital Boston, Harvard Medical School, Boston, Mass.

Correspondence to Francis X. McGowan, Jr, MD, Department of Anesthesiology, Perioperative and Pain Medicine, Children’s Hospital Boston, 300 Longwood Ave, Enders 1210, Boston, MA 02115. E-mail francis.mcgowan{at}childrens.harvard.edu

Received March 5, 2009; accepted July 2, 2009.

Background— Progressive left ventricular (LV) dysfunction can be a major late complication in patients with chronic right ventricular pressure overload (eg, tetralogy of Fallot). Therefore, we examined LV function (serial echocardiography and ex vivo Langendorff) and histology in a model of infant pressure-load right ventricular hypertrophy (RVH).

Methods and Results— Ten-day-old rabbits (n=6 per time point, total n=48) that underwent pulmonary artery banding were euthanized at 2 to 8 weeks after pulmonary artery banding, and comparisons were made with age-matched sham controls. LV performance (myocardial performance index) decreased during the progression of RVH, although the LV ejection fraction was maintained. In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic and end-diastolic dimensions, resulting in LV diastolic dysfunction with the appearance of preserved ejection fraction. Significant septal and LV free-wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson trichrome stain), and reduced capillary density (CD31 immunostaining) occurred in the pulmonary artery banding group after 6 to 8 weeks (all P<0.05).

Conclusion— This is the first study showing that pressure overload of the right ventricular resulting in RVH causes LV diastolic dysfunction while preserving ejection fraction through mechanical and molecular effects on 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: right ventricular hypertrophy • heart failure with preserved ejection fraction • diastolic dysfunction • apoptosis • hypertrophy • right ventricle

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