Key result
Progressive pulmonary vascular obstruction induces CTEPH and RV dysfunction in a 5-week porcine model.
Why the study?
An original piglet model of CTEPH associated with chronic right ventricular dysfunction was needed to reproduce human disease aspects and enable mechanistic and therapeutic studies.
The development of a novel piglet model of CTEPH successfully replicates human disease characteristics, offering a valuable tool for future therapeutic and mechanistic studies.
May advance preclinical CTEPH research in piglets; leaves open translation to human RV dysfunction without validation.
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.
No takes yet. Share an insight, caveat, or question.
Noly et al. (2015) studied Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Progressive obstruction of the pulmonary vascular bed vs. Sham animals was evaluated on Mean Pulmonary Arterial Pressure (mPAP), Right Atrial pressure, and Pulmonary Vascular Resistances (PVR). Progressive obstruction of the pulmonary vascular bed in piglets over 5 weeks successfully induced chronic thromboembolic pulmonary hypertension with right ventricular dysfunction.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: