title: Chronic Thromboembolic Pulmonary Hypertension and Assessment of Right Ventricular Function in the Piglet.
abstract: An original piglet model of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) associated with chronic Right Ventricular (RV) dysfunction is described. Pulmonary Hypertension (PH) was induced in 3-week-old piglets by a progressive obstruction of the pulmonary vascular bed. A ligation of the left Pulmonary Artery (PA) was performed first through a mini-thoracotomy. Second, weekly embolizations of the right lower pulmonary lobe were done under fluoroscopic guidance with n-butyl-2-cyanoacrylate during 5 weeks. Mean Pulmonary Arterial Pressure (mPAP) measured by ritght heart catheterism, increased progressively, as well as Right Atrial pressure and Pulmonary Vascular Resistances (PVR) after 5 weeks compared to sham animals. Right Ventricular (RV) structural and functional remodeling were assessed by transthoracic echocardiography (RV diameters, RV wall thickness, RV systolic function). RV elastance and RV-pulmonary coupling were assessed by Pressure-Volume Loops (PVL) analysis with conductance method. Histologic study of the lung and the right ventricle were also performed. Molecular analyses on RV fresh tissues could be performed through repeated transcutaneous endomyocardial biopsies. Pulmonary microvascular disease in obstructed and unobstructed territories was studied from lung biopsies using molecular analyses and pathology. Furthermore, the reliability and the reproducibility was associated with a range of PH severity in animals. Most aspects of the human CTEPH disease were reproduced in this model, which allows new perspectives for the understanding of the underlying mechanisms (mitochondria, inflammation) and new therapeutic approaches (targeted, cellular or gene therapies) of the overloaded right ventricle but also pulmonary microvascular disease.
authors.affiliation: Surgical Research Lab, Marie Lannelongue Hospital.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Noly
authors.affiliation: Surgical Research Lab, Marie Lannelongue Hospital; Thoracic and Cardiovascular Surgery, University Hospital of Rennes; julienguihaire@gmail.com.
authors.forename: Julien
authors.initials: J
authors.lastname: Guihaire
authors.affiliation: Surgical Research Lab, Marie Lannelongue Hospital.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Coblence
authors.affiliation: Department of Pathology, Marie Lannelongue Hospital; INSERM U999 Paris-Sud University.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.affiliation: Surgical Research Lab, Marie Lannelongue Hospital; Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital.
authors.forename: Elie
authors.initials: E
authors.lastname: Fadel
authors.affiliation: Surgical Research Lab, Marie Lannelongue Hospital; Department of Thoracic and Vascular Surgery, Marie Lannelongue Hospital.
authors.forename: Olaf
authors.initials: O
authors.lastname: Mercier
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004452:Echocardiography; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D011651:Pulmonary Artery / Q000503:physiopathology; D015203:Reproducibility of Results; D013552:Swine; D014655:Vascular Resistance; D018497:Ventricular Dysfunction, Right / Q000000981:diagnostic imaging / Q000503:physiopathology*