Hemodynamic and histological progression in the Sugen-Hypoxia Rat Model

Introduction: The sugen/hypoxia (SuHx) rat model of pulmonary arterial hypertension (PAH) replicates much of the pathology seen in the clinical disease. Aim: To determine the severity of the pulmonary vascular hemodynamics, vascular remodeling and increase in right heart size over a 13-week period in the Su/Hx model. Methods: Male Sprague Dawley rats received subcutaneous Su5416 (20 mg/kg) and inhaled Hx for 3-weeks (10% O2) followed by normoxic (Nx) air (21 % O2) for 5-, 8- or 10-weeks for a total duration of 8-, 11- or 13-weeks. At 8-, 11- and 13-weeks, pulmonary arterial blood pressure (PAP), right ventricular systemic pressure (RVSP), Fulton index (FI) and pulmonary vascular histology (vascular wall thickness, percent muscularization and obstruction of blood vessels) were measured. Results: PAP in the 8-week SuHx rats (30.4 mmHg) was higher than in the 11-week (26.6 mmHg) and 13-week (23.7 mmHg) rats. A similar trend was found for the wall thickness and percentage of muscularization of pulmonary arteries with highest values in the 8-week SuHx rats. The percentage of fully-occluded pulmonary blood vessels was, however, greater in the 13-week animals. There were no differences in the FI between the 8-, 11- and 13-week Su/Hx challenged rats. Conclusions: Values for PAP, wall thickness and muscularization of pulmonary arteries were highest at 8-weeks post Su-injection and regressed to lower values over 13-weeks. Conversely, the percentage of obliterated pulmonary vessels worsened over 13-weeks. These changes in pulmonary vascular hemodynamics, wall thickness and muscularization of pulmonary arteries over time did not correlate to the Fulton index that was unchanged over time.