Anne-Marie Koop

2 33 significantly regulated genes) was performed, allowing detection of significant regulation of gene sets, even if the expression of individual genes is not significantly different between groups. Statistical analysis Quantitative data are expressed as mean±standard error of the mean (SEM). Testing of differences between CON, PAB- and PAB+CF was performed using ANOVA with Bonferroni post hoc correction for multiple testing. The rats that survived 11 weeks of PAB (n=3) were not included in the PAB- group so that the time exposed to PAB was equal in the PAB- and PAB+CF groups and potential confounding of the results by time-differences was avoided. 22 Retrospective PAB- vs. PAB+CF comparisons at the 5 week time point were evaluated using t-tests. P<0.05 was considered significant (PASW Statistics 20 for Windows, SPSS, Chicago, Illinois). Statistical analysis of the transcriptome array is described separately in the online-only Data Supplement. RESULTS After a mean period of 52±5 days, 42% of the rats developed clinical RVF (5/12, figure 1b ). Tightness of PABwas similar in rats with or without signs of clinical RVF, assessed by peak RV pressure that was equally increased in both groups at 5 weeks (echo- measured PAB gradient ( figure 1c ) as well as at termination (invasively measured RV pressure, figure 1d ). Figure 1. A Schematic overview of experimental set-up. B Clinical symptoms of RV failure. Solid box = symptoms present. Open box = symptoms absent. Each row represents 1 rat. ABCDE refer to: A activity and appearance, B bodyweight, C cyanosis and/or hampered peripheral circulation, D dyspnea and/ or tachypnea, E effusions: pleural or ascites (see supplement for details). C PAB gradient measured by echocardiography at 5 weeks after surgery. D Invasively measured RV peak pressure measured before termination. Mean±SEM. Arrows indicate p<0.05 between respective groups.