title: Piglet model of chronic pulmonary hypertension.
abstract: None of the animal models have been able to reproduce all aspects of CTEPH because of the rapid resolution of the thrombi in the pulmonary vasculature. The aim of this study was to develop an easily reproducible large-animal model of chronic pulmonary hypertension (PH) related to the development of a postobstructive and overflow vasculopathy. Chronic PH was induced in 5 piglets by ligation of the left pulmonary artery (PA) through a midline sternotomy followed by weekly transcatheter embolization of the right lower-lobe arteries. Sham-operated piglets (n = 5) served as controls. Hemodynamics, RV function, lung morphometry, and endothelin-1 (ET-1) pathway gene expression (ET-1 and its receptors ETA and ETB) were assessed after 5 weeks in the obstructed (left lung and right lower lobe) and unobstructed (right upper lobe) territories. All animals developed chronic PH within 5 weeks. Compared to controls, chronic-PH animals had higher mean PA pressure (28.5 ± 1.7 vs. 11.6 ± 1.8 mmHg, P = 0.0001) and total pulmonary resistance (784 ± 160 vs. 378 ± 51 dyn s(-1) cm(-5), P = 0.05). Echocardiography showed RV enlargement, RV wall thickening (56 ± 5 vs. 30 ± 4 mm, P = 0.0003), decreased tricuspid annular plane systolic excursion (11.3 ± 0.9 vs. 14.4 ± 0.4 mm, P = 0.01), and paradoxical septal motion. In obstructed territories, morphometry demonstrated increases in the number of bronchial arteries per bronchus (8.7 ± 0.9 vs. 2 ± 0.17, P < 0.0001) and in distal PA media thickness (60% ± 2.8% vs. 29% ± 0.9%, P < 0.0001), consistent with postobstructive vasculopathy. Distal PA media thickness was increased in unobstructed territories (70% ± 2.4% vs. 29% ± 0.9%, P < 0.0001). ET-1 was overexpressed in unobstructed territories, compared to controls and obstructed territories. In conclusion, the large-animal model described here is reproducible and led to the development of PH in a relatively short time frame.
authors.affiliation: Centre Chirurgical Marie Lannelongue, Paris-Sud University, Service de Chirurgie Thoracique, Vasculaire et de Transplantation cardio-pulmonaire, Le Plessis-Robinson, France ; Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
authors.affiliation: Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Adriano
authors.initials: A
authors.lastname: Tivane
authors.affiliation: Centre Chirurgical Marie Lannelongue, Paris-Sud University, Service de Chirurgie Thoracique, Vasculaire et de Transplantation cardio-pulmonaire, Le Plessis-Robinson, France ; Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Marc
authors.initials: M
authors.lastname: de Perrot
authors.affiliation: Centre Chirurgical Marie Lannelongue, Paris-Sud University, Service de Chirurgie Thoracique, Vasculaire et de Transplantation cardio-pulmonaire, Le Plessis-Robinson, France.
authors.forename: François
authors.initials: F
authors.lastname: Raoux
authors.affiliation: Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Decante
authors.affiliation: Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.affiliation: Centre Chirurgical Marie Lannelongue, Paris-Sud University, Service de Chirurgie Thoracique, Vasculaire et de Transplantation cardio-pulmonaire, Le Plessis-Robinson, France ; Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dartevelle
authors.affiliation: Centre Chirurgical Marie Lannelongue, Paris-Sud University, Service de Chirurgie Thoracique, Vasculaire et de Transplantation cardio-pulmonaire, Le Plessis-Robinson, France ; Laboratoire de recherche chirurgicale and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 999, Le Plessis-Robinson, France.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
keywords: animal model; chronic thromboembolic pulmonary hypertension; pulmonary hypertension