Introduction: The SU5416+Hypoxia (SuHx) rat model a commonly used model of severe pulmonary arterial hypertension (PAH). Previous studies have shown that to induce PH in rats, administration of SU5416 alone is insufficient, but when administered together with a second hit such as hypoxia or immune modification, severe angioproliferative PH will ensue. Abnormal pulmonary blood flow (PBF) has since long been known to invoke pathological changes in the pulmonary vasculature. We tested the hypothesis that a combination of SU5416 administration and a left pneumonectomy (PNx) to induce an abnormal PBF in the contralateral lung is sufficient to induce severe PAH. Methods: Sprague Dawley rats were subjected to standard SuHx protocol (SU5416 / 4 weeks of hypoxia) or SuPNx protocol (SU5416 + PNx). Comparisons between models were made at week 2 and 6. Results: Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6. Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. Conclusion: This study described the SuPNx model which features severe PAH at 6 weeks and could serve as an alternative to the SuHx model. Our study together with previous studies on experimental models of pulmonary hypertension shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover and ongoing apoptosis represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature.
- Pulmonary hypertension
- Copyright © 2016, American Journal of Physiology - Lung Cellular and Molecular Physiology