Right ventricular diastolic adaptation to pressure overload in different rat strains

Abstract

Abstract Background Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been performed to test differences in RV response to pressure overload between rat strains. Purpose We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar, Sprague Dawley, and Fischer344 rats by hemodynamic profiling focusing on diastolic function. Methods Age-matched male rat weanlings were randomized to sham operation (Wistar sham, n=5; Sprague Dawley sham, n=4; Fischer344 sham, n=4) or PTB (Wistar PTB, n=8; Sprague Dawley PTB, n=8; Fischer344 PTB, n=8). RV function was evaluated after five weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements and RV remodelling assessed by histological analyses. Results At end of study, Fischer344 rats weighed 25 % less than Wistar and Sprague Dawley rats. PTB increased RV systolic pressures four-fold, and RV failure was evident by a decrease in cardiac index (Wistar PTB: 1.8±0.2 mL/s/m2 vs. Wistar sham: 3.9±0.2 mL/s/m2, p<0.0001; Sprague Dawley PTB: 1.7±0.1 mL/s/m2 vs. Sprague Dawley sham: 3.0±0.3 mL/s/m2, p=0.0029; Fischer344 PTB: 2.1±0.2 mL/s/m2 vs. Fischer344 sham: 3.8±0.3 mL/s/m2, p<0.0001). There was a 2.4-fold increase in RV end-systolic volume index in Wistar PTB and Sprague Dawley PTB compared with sham, while Fischer344 PTB rats were less affected with only a 2.0-fold increase in RV end-systolic volume index compared with Fischer344 sham. Diastolic and right atrial impairment were evident by increased end-diastolic elastance, filling pressure, and E/e’ in PTB rats compared with sham, again Fischer344 PTB the least affected. PTB increased RV fibrosis in all groups compared with sham, though Fischer344 PTB showed a trend towards a smaller increase in RV fibrosis (Fischer344 PTB: 9.2±0.4 % vs Wistar PTB: 10.7±0.2 %, p=0.0919). Conclusions PTB caused RV failure in all rats subjected to the procedure including signs of diastolic dysfunction. Despite similar increase in RV systolic pressure, Fischer344 PTB rats showed less RV dilatation and where more able to sustain diastolic function compared with Wistar and Sprague Dawley PTB rats. All three rat strains are suitable for PTB and studies of RV failure.