Echocardiographic Assessment of Pulmonary Hemodynamics and Right Ventricular Performance in Neonatal Murine Hypoxia

Background: Right heart catheterization (RHC) is the gold-standard for diagnosis of pulmonary hypertension (PH) but is a terminal procedure in neonatal mice. The objective was to validate echocardiographic measures of PH to establish the diagnostic capability against pulmonary vascular histology in neonatal mice. Methods: Adult mice, exposed to hypoxia or normoxia, were assessed by echocardiography and RHC to evaluate right ventricle (RV) morphometry and function. Echocardiographic measures identified in adult mice were then used to evaluate PH characteristics in hypoxia-exposed neonatal mice. Physiological parameters were compared to histopathology in all mice. Results: Hypoxia-challenged adult mice developed PH with RHC, demonstrating confirmed elevated RV systolic pressure (RVSP), RV hypertrophy, and increased cross-sectional area and neomuscularization of pulmonary vessels. Echocardiography-derived RV free wall (RVFW) thickness correlated with RV mass. Tricuspid valve annulus tissue Doppler imaging (TV TDI), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery acceleration measures (PAAT), and TAPSE × PAAT (a measure of RV work) all correlated with RVSP determined by RHC. In neonatal mice exposed to hypoxia, PAAT, TV TDI, TAPSE, and TAPSE × PAAT were decreased and RVFW thickness was increased, correlating with the histologic phenotype of PH. Conclusions: Echocardiographic indices of RV morphology and function provide reliable estimates of invasive RV hemodynamics in hypoxia-induced PH.