Understanding longitudinal bi-ventricular structural and functional changes in a Pulmonary Hypertension Sugen-Hypoxia rat model by Cardiac Magnetic Resonance Imaging

Cardiac MR (CMR) derived ventricular variables are predictive of mortality in pulmonary arterial hypertension (PAH). Rodent models which emphasize ventricular function, allowing serial monitoring are needed to identify pathophysiological features and novel therapies for PAH. We investigated longitudinal changes in the Sugen-hypoxia (SuHx) model during disease progression. Sprague Dawley rats (n=32) were divided into 2 groups. 1)Sugen-hypoxia; a dose of subcutaneous Sugen-5416 and placed in hypobaric hypoxia for 2 weeks followed by normoxia for 3 weeks. 2)Normoxia; maintained at normal pressure for 5 weeks. Rats were examined at 5 or 8 weeks with right-heart catheter, CMR and autopsy. Compared to normoxic controls (23.9±4.1 mmHg) RV systolic pressure was elevated in SuHx rats at 5 and 8 weeks (40.9±15.5 mmHg p=0.026, 48.9±9.6 mmHg p=0.002). RV end-systolic volume index was increased in 8 weeks SuHx (0.28±0.04 mlcm-2 p=0.003) compared to normoxic controls (0.18±0.03 mlcm-2). There was progressive dilatation of the RV at 8 weeks SuHx compared to normoxic controls (0.75±0.13 mlcm-2 vs 0.56±0.1 mlcm-2 p=0.02). Ventricular mass index by CMR at 5 weeks (0.34±0.06 vs p=0.003) and 8 weeks SuHx (0.34±0.06 p=0.002) were higher than normoxic controls (0.21 ± 0.04). Stroke volume, RV ejection fraction and LV variables were preserved in SuHx. Ventricular changes during the course of illness in a PAH rodent model can be examined by CMR. These changes including RV hypertrophy and subsequent dilatation are similar to those seen in PAH patients. Despite the persisting PH, there are features of adaptive cardiac remodelling through the study duration.