Early versus late cardiac remodelling during right ventricular pressure load and impact of preventive versus rescue therapy with endothelin-1 receptor blockers

Background: Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis and apoptosis which are attenuated by endothelin-1 (ET1) receptor blockade (ERB). Little is known about the time-course of remodelling and whether early versus late ERB confers improved outcome. Materials and methods: PAB was performed in 5-groups of rabbits: Shams, 3W (3-weeksPAB), 6W (6-weeksPAB), 6WERB1 (6-weeksPAB+ERB from day-1) and 6WERB21 (6-weeksPAB+ERB from day-21). Biventricular development of pro-fibrotic molecular signaling, fibrosis, apoptosis and conductance catheter and echocardiography function were studied. Results: Thirty-three rabbits (n=6-7/group; 3.00{plus minus}0.23kg) developed half to full-systemic RV pressures. Biventricular pro-fibrotic signaling and collagen deposition (RV-collagen: Shams 3.8{plus minus}0.58 vs. 3W 8.69{plus minus}2.52 vs. 6W 8.83{plus minus}4.02%, p<0.005) and apoptosis (RV- Shams 8.32{plus minus}3.2 vs. 3W 55.95{plus minus}47.55 vs. 6W 38.85{plus minus}...