Comparison of Aneurysm Patency and Mural Inflammation in an Arterial Rabbit Sidewall and Bifurcation Aneurysm Model under Consideration of Different Wall Conditions

Abstract

Background: Biological processes that lead to aneurysm formation, growth and rupture are insufficiently understood. Vessel wall inflammation and degeneration are suggested to be the driving factors. In this study, we aimed to investigate the natural course of vital (non-decellularized) and decellularized aneurysms in a rabbit sidewall and bifurcation model. Methods: Arterial pouches were sutured end-to-side on the carotid artery of New Zealand White rabbits (vital [n = 6] or decellularized [n = 6]), and into an end-to-side common carotid artery bifurcation (vital [n = 6] and decellularized [n = 6]). Patency was confirmed by fluorescence angiography. After 28 days, all animals underwent magnetic resonance and fluorescence angiography followed by aneurysm harvesting for macroscopic and histological evaluation. Results: None of the aneurysms ruptured during follow-up. All sidewall aneurysms thrombosed with histological inferior thrombus organization observed in decellularized compared to vital aneurysms. In the bifurcation model, half of all decellularized aneurysms thrombosed whereas the non-decellularized aneurysms remained patent with relevant increase in size compared to baseline. Conclusions: Poor thrombus organization in decellularized sidewall aneurysms confirmed the important role of mural cells in aneurysm healing after thrombus formation. Several factors such as restriction by neck tissue, small dimensions and hemodynamics may have prevented aneurysm growth despite pronounced inflammation in decellularized aneurysms. In the bifurcation model, rarefication of mural cells did not increase the risk of aneurysm growth but tendency to spontaneous thrombosis.

In situ decellularization of a large animal saccular aneurysm model: sustained inflammation and active aneurysm wall remodeling

“…Inflammation was observed only at 2 weeks after elastase incubation. The use of decellularization in surgical graft aneurysms has been recently reported in rabbits, 7 with similar finding of increased inflammation in the decellularized aneurysms. However, unlike the surgical model, this endovascular model does not involve vascular response to suturing at the neck.…”

“…However, a short time after aneurysm creation, 3 these models develop into stable aneurysms that do not demonstrate characteristics of vulnerable aneurysms in humans-namely, inflammation, intramural hemorrhage, and ultimately, rupture (reviewed in Tulamo et al 4 ), showing only some areas of thin, acellular aneurysm wall. 5 To deal with these model limitations, an innovative strategy has been developed to implant decellularized arterial grafts in rodents 6 and rabbits, 7 the former model showing both growth and rupture of these aneurysms. The objective of our study is to explore the feasibility of inducing in situ decellularization in a common rabbit model of saccular aneurysms 8 to recapitulate pathological features of unstable aneurysms and to perform comparative longitudinal non-invasive MRI of the inflammation marker myeloperoxidase (MPO).…”

Aspirin treatment prevents inflammation in experimental bifurcation aneurysms in New Zealand White rabbits

“…Furthermore, in a sidewall rabbit model, all aneurysms thrombosed spontaneously. 19 In our bifurcation series, in the ASA arm all aneurysms had partial thrombosis whereas the group without ASA had complete thrombosis in half of the aneurysms and partial thrombosis in the other half. Graft decellularization by SDS, including endothelial cells, may have contributed substantially to this high rate of thrombosis.…”

Experimental and Clinical Treatment of Subarachnoid Hemorrhage after the Rupture of Saccular Intracranial Aneurysms

“…The call for papers on this topic was met with a great response by researchers and clinicians from all over the world. Among 16 basic science and clinical research submissions, our editorial team selected nine articles for publication after extensive peer review, which included three original papers [ 1 , 2 , 3 ], three reviews [ 4 , 5 , 6 ], two case reports [ 7 , 8 ] and one technical note [ 9 ]. The remaining seven papers were not included, thus yielding a 44% rejection rate.…”

“…In an original study using an extracranial aneurysm model in rabbits, researchers confirmed that, under flow conditions in a bifurcation aneurysm, the organization of an intraluminal thrombus was strongly dependent on the condition of the aneurysm wall [ 2 ]. In another original work featuring an intracranial aneurysm model on rats, authors investigated how sex hormones influence the inflammatory reactions in the aneurysm walls and affect the endothelial cells of the vascular walls [ 3 ].…”