TY - JOUR T1 - In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling JF - Journal of NeuroInterventional Surgery JO - J NeuroIntervent Surg DO - 10.1136/neurintsurg-2020-016589 SP - neurintsurg-2020-016589 AU - Robert M King AU - Jildaz Caroff AU - Erin T Langan AU - Anita Leporati AU - Aurora Rodriguez-Rodriguez AU - Christopher M Raskett AU - Suresh Gupta AU - Ajit S Puri AU - Peter Caravan AU - Matthew J Gounis AU - Alexei A Bogdanov, Jr. Y1 - 2020/10/05 UR - http://jnis.bmj.com/content/early/2020/10/05/neurintsurg-2020-016589.abstract N2 - Objective To investigate in situ decellularization of a large animal model of saccular aneurysm as a strategy for achieving aneurysmal growth and lasting inflammation.Methods 18 New Zealand White rabbits were randomized 2:1 to receive endoluminal sodium dodecyl sulfate infusion (SDS, 1% solution, 45 min) following elastase or elastase-only treatment (control). All aneurysms were measured by digital subtraction angiography every 2 weeks. Every 2 weeks, three of the rabbits (two elastase + SDS, one control) underwent MRI, followed by contrast injection with myeloperoxidase (MPO)-sensing contrast agent. MRI was repeated 3 hours after contrast injection and the enhancement ratio (ER) was calculated. Following MRI, aneurysms were explanted and subjected to immunohistopathology.Results During follow-up MRI, the average ER for SDS-treated animals was 1.63±0.20, compared with 1.01±0.06 for controls (p<0.001). The width of SDS-treated aneurysms increased significantly in comparison with the elastase aneurysms (47% vs 20%, p<0.001). Image analysis of thin sections showed infiltration of MPO-positive cells in decellularized aneurysms and surroundings through the 12-week observation period while control tissue had 5–6 times fewer cells present 2 weeks after aneurysm creation. Immunohistochemistry demonstrated the presence of MPO-positive cells surrounding decellularized lesions at early time points. MPO-positive cells were found in the adventitia and in the thrombi adherent to the aneurysm wall at later time points.Conclusions In situ decellularization of a large animal model of saccular aneurysms reproduces features of unstable aneurysms, such as chronic inflammation (up to 12 weeks) and active aneurysm wall remodeling, leading to continued growth over 8 weeks. ER -