Evaluation of an endovascular aneurysm model in pigs for chronic experiments

Abstract

Background and aims: Cerebral aneurysms are a potentially life-threatening condition for humans. Due to the anatomical variability of different aneurysm types in human patients, animal models are indispensable for endovascular research. The aim of our study was to evaluate an endovascular aneurysm model in chronical experiments using 12 female Aachen minipigs.

Materials and methods: For aneurysm creation in external carotid and subclavian arteries, Amplatzer vascular plugs were used as occlusion devices, leaving simple stumps that serve as surrogate aneurysms. If necessary and anatomically possible, additional embolic materials, such as coils and liquid embolic agents were used.

Results: We created 42 aneurysms. Aneurysm creation was possible without complications in all cases. There was no spontaneous thrombosis of fabricated aneurysms. Complete perfusion arrest behind the fabricated aneurysm was challenging but achieved in 45% of cases. We were not able to identify significant factors that have an impact on the persisting perfusion of fabricated aneurysms on final imaging, particularly not the presence of side branches in the aneurysm lumen (P = 0.734) or volumes of the fabricated aneurysms (P = 0.620). Albeit not significant, the use of additional occlusive measures (coils, liquid embolic agents) and antithrombotic drugs (ASA, heparin and tirofiban) may be factors for persisting perfusion: Perfusion arrest behind the fabricated aneurysm was twice as high in animals treated with ASA and heparin compared to animals treated with ASA, heparin, and tirofiban (48% vs. 22%; P = 0.149).

Conclusion: Despite its limitations, including persistent perfusion and impaired predictability for long-term experiments, the endovascular aneurysm model shows potential to replace certain surgical models and offers broad applications in biomedical research and aneurysm therapy.

Keywords: Aachen minipig; endovascular animal model; external carotic artery; intracranial in vivo model; neuroradiology; subclavian artery.

Figure 1

Endovascular creation of artificial aneurysms: Schematic drawings of the fabricated aneurysms on the left (a and c) and corresponding digital subtraction angiography images during initial experimental setup on the right (b and d). For aneurysm creation, Amplatzer vascular plugs (black arrow) were inserted into target vessels to create a vessel stump that serves as an artificial aneurysm. Porcine external carotid (a and b) and subclavian (c and d) arteries were used as target vessels. Additional coils were used in the first case (a and b) to ensure full target vessel occlusion (white arrow)

Figure 2

Schematic drawing of the evolution of aneurysms during the chronic course: The six chronic aneurysms showed different initial and final outcomes. (a) Depicts a full perfusion arrest behind the aneurysm on initial experimental imaging, which yielded three different outcomes at angiography after 6 months: (b) Re-perfusion, (c) complete perfusion arrest, and (d) incomplete perfusion arrest. (e) Depicts persisting perfusion after the aneurysm on initial experimental imaging, which yielded two different outcomes at angiography after 6 months: (f) Re-perfusion and (g) complete perfusion arrest

Figure 3

Angiographic outcomes of chronic aneurysms during initial and final angiographies: a-d: Schematic drawing of a fabricated aneurysm in the left subclavian artery with complete perfusion arrest on initial imaging (a and b) and 6-month follow-up (c and d). (a and c) represent schematic drawings of the corresponding angiography images (b and d). e-h: Schematic drawing of a fabricated aneurysm in the left subclavian artery with perfusion on initial imaging (e and f) and 6-month follow-up (c and d). (e and g) represent schematic drawings of the corresponding angiography images (f and h)