Abstract 17280: A New in vivo Imaging Protocol for Non-Invasive Detection of Right Ventricular Dysfunction in a Pulmonary Hypertension Mouse Model

Abstract

Introduction: Accurate measurements of right ventricular (RV) function are critical for studying novel therapies impacting the heart and pulmonary circulation. Until now, assessment in mouse models has relied on invasive measures. Improvements in mouse echocardiography may facilitate application of measures recently validated in humans, including tricuspid annular plane systolic excursion (TAPSE) and RV-S’ (systolic excursion velocity), to allow non-invasive assessment of RV function. Aims: To apply and validate TAPSE and RV-S’ using high-resolution echocardiography for the measurement of RV function in a mouse model of pulmonary hypertension (PH). Methods: Echocardiography was performed on mice 3 weeks after induction of PH using inhaled bleomycin or saline control. PAT, TAPSE and RV-S’ were recorded in mice using a 55-mHz transducer (Visualsonics, Vevo3100). Invasive measurements of right ventricular systolic pressure (RVSP) were obtained via catheterisation of the internal jugular vein, prior to culling. Results: RVSP was significantly elevated in bleomycin-treated mice ( 33.41±0.8mmHg n=10) compared to controls ( 25.66±0.9mmHg n=11; p<0.0001). Similarly, RV hypertrophy was observed in bleomycin mice [RV:body weight 1.156±0.03g/kg n=11] compared with control ( 0.968±0.02g/kg n=12; p=0.0002). TAPSE was sensitive to these differences, being significantly reduced in bleomycin mice ( 0.5739±0.020mm n=8) compared with control ( 0.7387±0.033mm n=10; p=0.0012), and correlated significantly with invasive RVSP (r 2 =0.7218; p<0.0001). RV-S’ was also reduced in bleomycin mice (18.14±0.98mm/s n=7) compared with control (25.38±1.24mm/s n=8; p=0.0006) and correlated strongly with RVSP (r 2 =0.6378; p=0.0011). The correlation of both TAPSE and RV-S’ with RVSP compared favourably to the previously used surrogate measure of RVSP in mice, PAT (r 2 =0.5278; p=0.0002). Conclusions: TAPSE and RV-S’ can be applied in mouse echocardiography, and are sensitive, non-invasive measures of PH and RV dysfunction, comparing well with gold-standard invasive right ventricular systolic pressures. This may benefit the power of future preclinical studies of novel therapies in pulmonary hypertension and RV dysfunction.