Anne-Marie Koop

2 41 Figure 7. Enrichment of gene sets associated with energy metabolism. Normalized enrichment scores (NES) of PAB- and PAB+CF vs. CON. N=7/4/5 for CON/PAB-/PAB+CF. * indicates false discovery rate (FDR) <15%, nominal P value <0.05 and normalized enrichment score >1.3 for respective gene set vs. CON. DISCUSSION In this study, the rat model of chronic ‘tight’ pulmonary artery banding induced RV failure in all rats, and severe RV failure with clinical symptoms in half of the rats. Progressive RV failure was characterized hemodynamically by progressive diastolic dysfunction. Diastolic dysfunction occurred despite adaptive responses to maintain active relaxation, and was not due to increased fibrosis. RV failure with clinical symptoms is associated with a hypoxia-prone cellular environment in the RV myocardium, increased intrinsic protective response to oxidative stress and suppressed myocardial metabolism. The here described approach to the PAB model gives insight in advanced (clinical) RVF due to increased pressure load and can be used to unravel the mechanisms involved in the progression from RV adaptation to RV failure and to assess the effect of interventions on these mechanisms.