Right Ventricular Pressure Overload Can Rescue Left Ventricular Dysfunction By Promoting Biventricular Adaptive Hypertrophy
Matteo Ponzoni, MD, Azadeh Yeganeh, Jennifer Zhang, Ramesh B. Vanama, Libo Zhang, Jing Li, Jason T. Maynes, John G. Coles.
The Hospital for Sick Children, Toronto, ON, Canada.
Objective(s): Pulmonary artery banding (PAB) has been reinvented as a therapy for left ventricular (LV) failure in pediatric dilated cardiomyopathy (DCM), however, the underlying mechanisms of action of PAB-induced LV rehabilitation are still mainly unknown. We established a translational small animal model of LV dysfunction rescued by PAB to document the macroscopic and tissue-level modifications in biventricular function and structure promoted by PAB.
Methods: Sprague-Dawley rats underwent left anterior descending (LAD) artery ligation (LV dysfunction model) followed by PAB 1 week later (LAD+PAB, n=15). Controls consisted of sham-operated (n=16), PAB-only (n=16), and LAD-only rats (n=16). The animals underwent weekly echocardiography and terminal histopathology 4 weeks after surgery. Data are presented as mean (standard deviation) and compared using ANOVA.
Results: Despite similar LV systo-diastolic dysfunction early after LAD ligation, LAD+PAB rats exhibited LV remodeling (LV end-diastolic area: 0.49(0.06)cm2 vs 0.59(0.1)cm2, p=0.040), improvement of LV ejection fraction (48(4.4)% vs 35.3(4.1)%, p<0.001), and amelioration of mitral valve inflow Doppler E/A (1.50(0.28) vs 1.90(0.21), p=0.048), compared to LAD-only animals. The histological analysis documented LV hypertrophy (LV thickness/body weight: 9.1(1.2)um/g vs 7.6(0.5)um/g, p=0.047), increased cardiomyocyte diameter (14.8(0.9)um vs 11.9(1)um, p=0.002), and reduced LV fibrosis (17.2(7.5)% vs 32.3(8.9)%, p<0.001) in LAD+PAB vs LAD-only animals.
Conclusions: In our novel translational model of LV dysfunction treated with PAB, PAB induced positive LV remodeling and improved LV systo-diastolic function. Right ventricular pressure overload stimulated a biventricular hypertrophic response that may constitute a potential compensatory mechanism able to rescue residual LV function and limit LV injury.
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