Progression of pulmonary arterial hypertension: A study in model

The pathophysiology of pulmonary arterial hypertension (PAH) is complex. Pathology and molecular biology signatures during its progression are interesting to study.

This study will describe PAH progression from the first until the fourth week in a model focussing on endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), extracellular signal-regulated kinase 1/2 (ERK1/2), intima media thickness (IMT), and proliferation of pulmonary arterial smooth muscle cells (PASMCs) and fibroblast.

Six male Wistar rats aged 4 months old with a range bodyweight (BW) of 180-230 g were used in this experiment. Rats were injected with Monocrotaline (MCT) 60 mg/kg of BW subcutaneously to induce PAH. Rats were anesthetized with Ketamin 50 mg/kg BW and Xylazin 5 mg/kg BW intramuscularly before cathetherization. Right heart cathetherization was performed at days 1st, 2nd, 4th, 9th, 16th, and 23rd after MCT injection. After completion of cathetherization, intracardiac exsanguination was performed and blood serum was analyzed by ELISA for ET-1, TNF-α, and ERK1/2. Lungs were harvested and parafinated blocked before being analyzed for IMT and proliferation of PASMCs and fibroblast.

At first until the second week after MCT injection, mean pulmonary arterial pressure fluctuated. However, after 3rd until 4th week after MCT injection, its value becomes established over 40 mmHg. This is also followed by the level of ET-1 over 78 pg/ml, level of TNF-α over 223 ng/l, level of ERK1/2 over 47 ng/ml, IMT over 42 µm, ratio of PASMCs over 65%, and ratio of fibroblast 30%-35%.

Pulmonary hypertension was established at week 3rd-4th after MCT injection in a model.