Introduction: Pulmonary arterial hypertension (PAH) is defined as group 1 of pulmonary hypertension and is expressed by elevated mean pulmonary artery pressure ≥ 20 mmHg, end-expiratory pulmonary artery wedge pressure ≤ 15mmHg, and pulmonary vascular resistance > 2 Wood units[1]. PAH is accompanied by increased right ventricular (RV) afterloads resulting in adaptive or maladaptive right ventricular remodeling. Thus, sensitive biomarkers for the early diagnosis of PAH are important to control disease progression by appropriate treatment. The purpose of the current study was to investigate whether indices of RV function and global longitudinal strain (GLS) derived by MRI can detect early onset of PAH in RV.

Method: The study contained two groups of male Sprague Dawley rats (n = 20; weight = 365 ± 50 grams): healthy controls (n=6); PAH diseased animals (n = 14, disease induction by a subcutaneous injection of 60 mg/kg Monocrotaline dissolved in 300 µl NaCl 0.9% and an additional, continuous oral application of Enrofloxacin 5 mg/kg). Cardiac and respiratory gated Cine-FLASH was performed at 11.7T (Bruker MR system BioSpec USR  117/16) using a surface loop coil with the following parameters: TR = 5 ms; TE = 2.5 ms; Flip-Angle = 8⁰; averages = 1; Matrix size = 234*234, slice-thickness = 1mm. All MR data were analyzed by using Segment Medviso AB (version 3.3 R10187c). As reference, tricuspid annular plane systolic excursion (TAPSE) by echocardiography and RV myocardial histopathology were conducted.

Results: To characterize our animal model of PAH in regard to associated RV load and function, TAPSE was measured over the course of time as well as the development of fibrosis in RV. TAPSE values were already reduced on day 7 compared to healthy controls, remained unchanged from day 7 to day 14 and further decreased afterwards. Along with these results, histopathological findings revealed significant fibrosis at day 7 in comparison to healthy controls but remained also unchanged until day 14 before they dramatically worsened at later stages. The right ventricular functional indices such as right ventricular-arterial coupling (VAC), ejection fraction (EF), stroke volume (SV) and GLS obtained by MRI altered significantly from day 0 to 6 post-induction (p<0.05). In addition, substantial changes were observed in the GLS values between day 6 and day 9. After day 9, the right heart function and strain reached to a plateau with no further changes until day 17.

Conclusion: Taken together our results showed that GLS was more sensitive to the disease progression of PAH at early stages of RV dysfunction, and thus could distinguish between day 6 to day 9, while other functional indices such as EF, SV, and VAC could not.