Right ventricular diastolic adaptation to pressure overload in different rat strains.

Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been made to test differences in RV response to pressure overload between rat strains. We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar (W), Sprague Dawley (SD), and Fischer344 (F) rats by hemodynamic profiling focusing on diastolic function. Age-matched male rat weanlings were randomized to sham surgery (W-sham, n = 5; SD-sham, n = 4; F-sham, n = 4) or PTB (W-PTB, n = 8; SD-PTB, n = 8; F-PTB, n = 8). RV function was evaluated after 5 weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure and increased RV systolic pressures four-fold in all three PTB groups compared with sham. W- and SD-PTB had a 2.4-fold increase in RV end-systolic volume index compared with sham, while F-PTB rats were less affected. Diastolic and right atrial impairment were evident by increased RV end-diastolic elastance, filling pressure, and E/e' in PTB rats compared with sham, again F-PTB the least affected. In conclusions, PTB caused RV failure with signs of diastolic dysfunction. Despite a similar increase in RV systolic pressure, F-PTB rats showed less RV dilatation and a more preserved diastolic function compared with W- and SD-PTB.

Right Atrial Adaptation to Precapillary Pulmonary Hypertension: Pressure-Volume, Cardiomyocyte, and Histological Analysis.

BACKGROUND: Precapillary pulmonary hypertension (precPH) patients have altered right atrial (RA) function and right ventricular (RV) diastolic stiffness. OBJECTIVES: This study aimed to investigate RA function using pressure-volume (PV) loops, isolated cardiomyocyte, and histological analyses. METHODS: RA PV loops were constructed in control subjects (n = 9) and precPH patients (n = 27) using magnetic resonance and catheterization data. RA stiffness (pressure rise during atrial filling) and right atrioventricular coupling index (RA minimal volume / RV end-diastolic volume) were compared in a larger cohort of patients with moderate (n = 39) or severe (n = 41) RV diastolic stiffness. Cardiomyocytes were isolated from RA tissue collected from control subjects (n = 6) and precPH patients (n = 9) undergoing surgery. Autopsy material was collected from control subjects (n = 6) and precPH patients (n = 4) to study RA hypertrophy, capillarization, and fibrosis. RESULTS: RA PV loops showed 3 RA cardiac phases (reservoir, passive emptying, and contraction) with dilatation and elevated pressure in precPH. PrecPH patients with severe RV diastolic stiffness had increased RA stiffness and worse right atrioventricular coupling index. Cardiomyocyte cross-sectional area was increased 2- to 3-fold in precPH, but active tension generated by the sarcomeres was unaltered. There was no increase in passive tension of the cardiomyocytes, but end-stage precPH showed reduced number of capillaries per mm2 accompanied by interstitial and perivascular fibrosis. CONCLUSIONS: RA PV loops show increased RA stiffness and suggest atrioventricular uncoupling in patients with severe RV diastolic stiffness. Isolated RA cardiomyocytes of precPH patients are hypertrophied, without intrinsic sarcomeric changes. In end-stage precPH, reduced capillary density is accompanied by interstitial and perivascular fibrosis.