70 Differential proteomic profiling and hemodynamic characterization of the pressure overloaded right ventricule in young rats: a novel approach

disease. We sought to determine the mechanisms underlying the progression from compensated RV hypertrophy to failure using an alternative approach. Therefore, we studied alterations in myocardial protein expression in relation to RV function. Here, we report the results after 6 weeks of RV pressure overload. Methods: Male Wistar rats (age 8.1=t=0.4 wk) underwent Pulmonary Artery Banding (PAB) (n=6) or sham (n=6) operation. Load(in)dependent RV and LV function was characterized in vivo by means of the end-systolic pressure-volume relation (ESPVR) using the conductance catheter technique. Myocardial cytoplasmatic protein expression was determined by proteomic analysis of individual homogenates of RV myocardium (6 gels per group ie. sham and PAB). Results: In PAB animals the ratio of RV and RA to body weight was increased (0.58±0.02 vs. 1.034-0.05 RV, p<0.001 and 0.13±0.01 vs. 0.21-4-0.03 RA rag/g, p<0.05). Hemodynmnics: Hypertrophic RV endsystolic and end-diastolic pressures were increased (31-t-1 vs. 65±5 and 4.34-0.5 vs. 10.54-1.l mmHg, p<0.001). After PAB cardiac output decreased significantly, but heart rate was unchanged. Load-dependent indices of RV systolic performance (dPdtMax and stroke work) increased significantly (p<0.001) as a result of PAB, as well as the loadindependent slope of the ESPVR (0.09±0.03 vs. 0.29±0.02 mmHg/bL, p<0.001). In contrast, indices of LV function were not affected. Proteomics: Several stress-and metabolic proteins significantly differing in intensity were identified. A general downregulation was observed in betaoxidation pathway proteins. Glycolytic pathway proteins showed an increased expression. Three spots were identified as HSP27 (+1.7-3.5 (in PAB), p<0.05), suggesting HSP27 modifications. Contusions: Our results indicate that 6 weeks of PAB leads to compensated RV hypertrophy in rats. Despite the enhanced RV contractile state, cardiac output falls, suggesting initial transition from compensated state to failure. In these conditions, specific alterations and modifications in metabolic and stress related protein expressions were present in the hypertrophic RV. We expect that alterations in myocardial protein expression (in eytoplasmatic and other subfractions) associated with the progression to RV failure will be disclosed in further studies.