Abstract 15228: Chronic Thromboembolic Pulmonary Hypertension (CTEPH): A Pig Model
Background: Repeated thromboembolic events of pulmonary arteries represent a critical factor for the development of severe CTEPH, which develops in about 5% of all cases of acute pulmonary embolism. The aim of our study was to develop a suitable large animal model mimicking the pathophysiology of CTEPH giving the opportunity to investigate new therapeutical options.
Methods: CTEPH was induced in 10 pigs (20±1 kg, 6-8 weeks) using a novel copper/scaffold system which was placed in the pulmonary artery under fluoroscopic guidance via a percutaneous approach followed by embolization with autologous thrombi. 500mg of tranexamic acid was administered twice daily. Hemodynamic parameters were assessed at baseline and after 4, 12 and 24 weeks, accompanied by magnetic resonance imaging (MRI) and computer tomography (CT) follow-up. After 24 weeks, histomorphometric analysis of pulmonary vessels was performed. 4 sham-operated pigs served as controls.
Results: A right ventricular hypertrophy was evident after 24 weeks. Lung regions without embolization were hyperperfused as assessed by CT angiography. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were increased after 4 weeks, peaking after 24 weeks (mPAP: control 18±0.6 vs. CTEPH 24 weeks 31±2.8 mmHg; PVRI: control 165±10 vs. CTEPH 24 weeks 462±93 dyn.sec.m2/cm5, p<0.05). Pulmonary capillary wedge pressure remained at baseline level, whereas cardiac index decreased over time in the CTEPH group. Small arteries in the hyperperfused lung regions demonstrated a significant wall thickening of the media in comparison to control tissue (percent wall thickness, CTEPH: 40±0.7% vs. control: 26±0.9%). Additionally, the inner diameter of these vessels was significantly decreased whereas the outer diameter did not change, compared to controls. Proliferation of vascular smooth muscle cells was increased in lung tissue of the CTEPH group.
Conclusion: The implantation of novel copper-based foreign bodies in the pulmonary arteries of pigs induces a chronic and progressive arterial obstruction and results in CTEPH with typical hemodynamic and morphologic alterations. This new animal model is suitable to investigate new therapeutic options for the treatment of CTEPH.
- © 2012 by American Heart Association, Inc.