Anne-Marie Koop

4 161 RESULTS RV pressure load induced RV dysfunction PAB induced a pressure load of the RV that increased over time ( figure 1a ) and echocardiographic markers of relevant pressure load were present ( suppl. table 1 ). In PAB-rats, TAPSE ( figure 1b ), RV dP/dt max ( figure 1c ) and RV dP/dt min ( figure 1d ) were reduced. RV end diastolic pressure ( figure 1e ) tended to increase at 2 weeks after PAB, but gradually decreased again over time. Cardiac index was maintained over 12 weeks in rats with PAB ( figure 1f ) and in line with that, these rats did not develop clinical signs of RV failure using the ABCDE-criteria. 8 Finally, RV workload ( suppl. table 1 ) and power ( figure 1g ) increased significantly in the PAB-groups, without changes over time. Pressure load induced RV remodelling PAB induced hypertrophy after 2 weeks, expressed by RVweight normalized for tibia length ( figure 1h ). RV cardiomyocyte cross sectional area ( figure 1i,j ) and capillary myocyte ratio ( figure 1k ) increased in PAB-rats compared to control and over time (5 and 12 weeks, vs. 2 weeks after PAB). The capillary density, irrespectively of the number of cardiomyocytes, decreased at all time points compared to control (21, 20 and 23, vs. 31.05 vessels per square millimeter) ( figure 1j ). RV fibrosis increased significantly compared to control only after 5 weeks of PAB ( figure 1j,l ), whereas gene expression of the fibrotic markers collagen subunits 1A2 (COL1A2) and 3A1 (COL3A1) and transforming growth factor β 1 (TGF β 1) and β 2 (TGF β 2) were all increased already 2 weeks after PAB and gradually decreased at 5 and 12 weeks ( figure 1m ). Gene expression of both natriuretic pro-peptide A (NPPA), as marker of myocardial stress, and the ratio of myosin heavy chain isoforms β and α ( suppl. table 2 ), as marker of the switch to fetal gene programme, were increased at all time points ( figure 1m ). Finally, gene expression of regulator of calcineurin 1 (RCAN1) involved in activation of hypertrophy was increased at 5 and 12 weeks ( figure 1m ).