Concurrent left ventricular pressure-loading improves right ventricular function, remodeling, and molecular signaling in response to pulmonary artery banding

Abstract Background Studies have established the significance of right ventricle (RV) function in individuals with many congenital heart diseases, however the impact of pressure overload (PO) on the RV, concomitant with changes in LV pressure, has yet to be fully understood. We have previously demonstrated that pulmonary artery banding (PAB) with simultaneous LVPO improved systolic function in both ventricles and reduced myocyte hypertrophy and collagen content compared to PAB alone1. These findings suggested that increasing LV afterload attenuated maladaptive RV remodeling and molecular signaling. Purpose We investigated whether the degree of LV afterload beneficially impacts RV function, remodeling, and molecular signaling pathways. Methods We established a model of double-banding (DB) in male Sprague-Dawley rats (n = 17) where the PA and transverse aorta were constricted with 16-gauge and 14-gauge needles, respectively. At 6-weeks post-surgery, Doppler-echocardiography was used to measure the flow velocity across the aortic constriction to divide the DB rats into moderate (DBMOD) and mild (DBMILD) groups. PAB-only (n=9) and Sham (n=9) groups were used as controls. All animals underwent echocardiography and cardiac catheterization 6-weeks post-surgery to assess RV/LV structure and hemodynamic function. Heart tissue was collected for Picrosirius red (PSR) staining to assess RV collagen content. Immunoblotting and RT-qPCR were used to quantify protein and transcripts of fibrosis and mechanotransduction pathways. Results Echocardiography identified increases in RV end-diastolic and end-systolic areas alongside a decrease in tricuspid annular plane systolic excursion (TAPSE) in PAB rats compared to shams. These changes were abrogated in DBMOD rats and to a lesser extent in DBMILD rats (p