251 Non-invasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension

Abstract

Genetically modified mice offer the unique opportunity to gain insights into the pathophysiology of pulmonary arterial hypertension (PAH). In mice, right heart catheterization is the only available technique to measure right ventricular systolic pressure (RVSP). However, it is a terminal procedure and does not allow serial follow-up. Our objective was to validate a non-invasive technique to assess RVSP in mice. Right ventricle catheterization and echocardiography were simultaneously performed in mice with pulmonary hypertension induced acutely by infusion of a thromboxane analogue, U-46619 or chronically by lung-specific over-expression of interleukin 6 (IL-6). In a subgroup of mice, echocardiography was performed using light anesthesia before catheterization. Pulsed-Doppler of pulmonary artery flow was recorded in the parasternal short axis view. Pulmonary acceleration time (PAT), and ejection time (ET) were measured. Infusion of U-46619 acutely increased RVSP, shortened PAT and decreased PAT/ET. The pulmonary flow pattern changed from symmetric at baseline to asymmetric at higher RVSPs. Transgenic IL-6 mice had high RVSP measured by catheter (39±7 mmHg), short PAT (17±4 ms) and low PAT/ET ratio (31±8%). The PAT correlated linearly with RVSP (r2=–0.67; p<0.0001), as did PAT/ET (r2=–0.76, p<0.0001). Sensitivity and specificity for detecting high RVSP (>32 mmHg) were 100% (7/7) and 86% (6/7), respectively, for both indexes (cutoff values: PAT <21 ms and PAT/ET <39%). PAT/ET measured during light anesthesia correlated with PAT/ET obtained during invasive catheterization (r2=0.87, p<0.0001). Intra-observer and inter-observer variability of PAT and PAT/ET were less than 6%. Pulmonary artery systolic pressure can be estimated noninvasively in mice. Echocardiography allows to monitor acute changes of RVSP and to detect pulmonary hypertension. This technique enables to follow PAH evolution easily and repeatedly in mice.Download : Download full-size image