Background: Inoperable chronic thromboemboli pulmonary hypertension (CTEPH) is one of the significant causes of severe PH. In this patient group possible treatment options are limited to chronic anticoagulation and lung transplantation with advanced medical therapy and percutaneous intervention offering uproven potential therapeutic avenues. A comprehensive animal model would allow for improved exploration of potential therapies. The few animal models developed to date have focused on very specific aspects of this multifaceted condition each with specific limitations.
Our aim was to generate a closed chest, stable, long-term animal model that will reproduce the central aspects of CTEPH.
Methods: Sexually mature female Sinclair minipgs were used. They underwent surgical splenectomy, after an interval of 2-4 weeks they commenced stepwise interventions where the pulmonary vasculature was plugged with vascular coils and/or Amplatzer plugs over a period of up to 6 months. Baseline and follow-up assessments were perfomed with biomarkers, echocardiography and invasive hemodynamics.
Results: Uncomplicated splenectomy was performed in 8 animals. All animals underwent implantation of a large occluder in the right main pulmonary artery. In a single case the device was deployed too proximal reslting in decompensation and death. During follow-upnormal animal weight gain was mild. Animals with rapid reduction of perfusion to larger pulmonary vascular beds did not increase in weight. All measured pressures were depressed due to anesthetic, An acute increase of ≥20 mmHg in mPAP resulted in hemodynamic embarrassment In most instances (post plugging), pulmonary angiography resulted in significant increase of mPAP to at least 50% of mSAP. In the presence of tricuspid incompetence, additional plugging resulted in hemodynamic instability.
Pathological assessment of the lungs is pending.
Conclusion: The creation of a long-term animal model of CTEPH using a combination of minipigs, splenectomy and stepwise selective plugging of the pulmonary vasculature appears promising.
