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Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats.
Happé, C M; de Raaf, M A; Rol, N; Schalij, I; Vonk-Noordegraaf, A; Westerhof, N; Voelkel, N F; de Man, F S; Bogaard, H J.
Afiliación
  • Happé CM; Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • de Raaf MA; Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • Rol N; Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • Schalij I; Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • Vonk-Noordegraaf A; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • Westerhof N; Department of Physiology, VU University Medical Center, Amsterdam, the Netherlands;
  • Voelkel NF; School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia.
  • de Man FS; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and.
  • Bogaard HJ; Department of Pulmonology, VU University Medical Center, Amsterdam, the Netherlands; and hj.bogaard@vumc.nl.
Am J Physiol Lung Cell Mol Physiol ; 310(11): L1088-97, 2016 06 01.
Article en En | MEDLINE | ID: mdl-27036867
ABSTRACT
The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. 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. This study describes the SuPNx model, which features severe PAH at 6 wk 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertensión Pulmonar Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2016 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hipertensión Pulmonar Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2016 Tipo del documento: Article