Abstract 5907: Development of Left Ventricular Dysfunction During Progression of Infant Right Ventricular Hypertrophy
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). The mechanisms remains unclear. 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) underwent pulmonary artery banding (PAB), were sacrificed at 2–8 weeks after PAB, and compared to age-matched sham controls. Both RV and LV performance (myocardial performance index, MPI; fractional area change, FAC), measured by echocardiography, decreased during the progression of RVH (Table⇓). In addition, RVH caused significant septal displacement, reduced septal contractility, and decreased LV end-systolic (LVDs) and diastolic (LVDd) dimensions. Significant septal and LV free wall apoptosis (myocyte-specific TUNEL and activated caspase-3), fibrosis (Masson’s Trichrome), and reduced capillary density (CD31 immunostaining) occurred in the left ventricles of the PAB group after 6 – 8 wks (all p<0.05).
Conclusion: This study for the first time shows that pressure overload resulting in RVH causes LV dysfunction by both mechanical and molecular effects upon the septum and LV myocardium. In particular, the development of RVH is associated with septal and LV apoptosis, pathologic LV remodeling, and reduced LV capillary density. Potential mediators and mechanisms (e.g. paracrine vs. circulating stimuli) merit further investigation