Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension.
BACKGROUND
Genetically modified mice offer the unique opportunity to gain insight into the pathophysiology of pulmonary arterial hypertension. 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 for serial measurements. Our objective was to validate a noninvasive technique to assess RVSP in mice.


RESULTS
Right ventricle catheterization and echocardiography (30-MHz transducer) were simultaneously performed in mice with pulmonary hypertension induced acutely by infusion of a thromboxane analogue, U-46619, or chronically by lung-specific overexpression of interleukin-6. Pulmonary acceleration time (PAT) and ejection time (ET) were measured in the parasternal short-axis view by pulsed-wave Doppler of pulmonary artery flow. Infusion of U-46619 acutely increased RVSP, shortened PAT, and decreased PAT/ET. The pulmonary flow pattern changed from symmetrical at baseline to asymmetrical at higher RVSPs. In wild-type and interleukin-6-overexpressing mice, the PAT correlated linearly with RVSP (r(2)=-0.67, P<0.0001), as did PAT/ET (r(2)=-0.76, P<0.0001). Sensitivity and specificity for detecting high RVSP (>32 mm Hg) were 100% (7/7) and 86% (6/7), respectively, for both indices (cutoff values: PAT, <21 ms; PAT/ET, <39%). Intraobserver and interobserver variability of PAT and PAT/ET were <6%.


CONCLUSIONS
Right ventricular systolic pressure can be estimated noninvasively in mice. Echocardiography is able to detect acute and chronic increases in RVSP with high sensitivity and specificity as well as to assess the effects of treatment on RVSP. This noninvasive technique may permit the characterization of the evolution of pulmonary arterial hypertension in genetically modified mice.
Thibault
Hélène B
HB
Cardiac Ultrasound Laboratory, Cardiology Division of Department of Medicine, Cardiovascular Research Center, Anesthesia Center for Critical Care Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Kurtz
Baptiste
B
Raher
Michael J
MJ
Shaik
Rahamthulla S
RS
Waxman
Aaron
A
Derumeaux
Geneviève
G
Halpern
Elkan F
EF
Bloch
Kenneth D
KD
Scherrer-Crosbie
Marielle
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D006328:Cardiac Catheterization; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler / Q000379:methods*; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011651:Pulmonary Artery / Q000503:physiopathology*; D012044:Regression Analysis; D012680:Sensitivity and Specificity
D015850:Interleukin-6; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid