Functional Magnetic Resonance Imaging For In Vivo Quantification Of Pulmonary Hypertension In The Sugen 5416/Hypoxia Mouse

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary artery pressures and right heart failure. Mouse models of PAH are instrumental in understanding the disease pathophysiology. However, few methods are available to evaluate right cardiac function in small animals. In this study, magnetic resonance imaging was used to measure in vivo cardiac dimensions in the Sugen 5416/hypoxia mouse model. Pulmonary hypertension (PH) was induced inC57BL/6 mice by 3weeks of exposure to 10% oxygen and vascular endothelial growth factor receptor inhibition (20 mg kg(-1) SU5416). Control mice were housed in room air and received vehicle(DMSO). Right ventricular pressures were recorded with apressure-conductance transducer. Short-axis contiguous 1-mm-thick slices were acquired through the heart and great vessels using a fast low-angle shot (FLASH)-cine sequence. Thirteen images were collected throughout each cardiac cycle. Right ventricular systolic pressure was elevated in PH mice (23.6 +/- 6 versus 41.0 +/- 11 mm Hg, control versus PH, respectively; P<0.001, n=5-11). Right ventricular wall thickness was greater in PH than in control mice at end diastole (0.30 +/- 0.05 versus 0.48 +/- 0.06 mm, control versus PH, respectively; P<0.01, n=6), but measurements were not different at end systole (control versus PH, 0.59 +/- 0.11 versus 0.70 +/- 0.11 mm, respectively). Right ventricular ejection fraction was decreased in PH mice (72 +/- 3 versus 58 +/- 5%, control versus PH, respectively; P<0.04, n=6). These data demonstrate that magnetic resonance imaging is a precise method to monitor right ventricular remodelling and cardiac output longitudinally in mouse models of PH.