From bench to bedside: utility of the rabbit elastase aneurysm model in preclinical studies of intracranial aneurysm treatment

Abstract

Preclinical studies are important in helping practitioners and device developers improve techniques and tools for endovascular treatment of intracranial aneurysms. Thus an understanding of the major animal models used in such studies is important. The New Zealand rabbit elastase induced arterial aneurysm of the common carotid artery is one of the most commonly used models in testing the safety and efficacy of new endovascular devices. In this review we discuss: (1) the various techniques used to create the aneurysm, (2) complications of aneurysm creation, (3) natural history of the arterial aneurysm, (4) histopathologic and hemodynamic features of the aneurysm, (5) devices tested using this model, and (6) weaknesses of the model. We demonstrate how preclinical studies using this model are applied in the treatment of intracranial aneurysms in humans. The model has similar hemodynamic, morphological, and histologic characteristics to human aneurysms, and demonstrates similar healing responses to coiling as human aneurysms. Despite these strengths, however, the model does have many weaknesses, including the fact that the model does not emulate the complex inflammatory processes affecting growing and ruptured aneurysms. Furthermore, the extracranial location of the model affects its ability to be used in preclinical safety assessments of new devices. We conclude that the rabbit elastase model has characteristics that make it a simple and effective model for preclinical studies on the endovascular treatment of intracranial aneurysms, but further work is needed to develop aneurysm models that simulate the histopathologic and morphologic characteristics of growing and ruptured aneurysms.

Keywords: Aneurysm; Device; Intervention; Subarachnoid; Technique.

Figure 1

Creation of Rabbit Elastase Aneurysm Model This cartoon illustrates the operative process used to create the rabbit elastase aneurysm model. Following exposure of the right carotid sheath and creation of a small arteriotomy, a sheath is introduced into the right common carotid artery. A balloon is introduced through the sheath and placed at the origin of the right common carotid artery and inflated. The right common carotid artery is ligated. Following this, elastase is introduced into the artery and allowed to incubate for 20 minutes. The sheath and balloon are then withdrawn and the superior aspect of the aneurysm is cinched off. The aneurysm continues to grow and then generally stabilizes at one month due to a combination of elastin digestion and hemodynamic forces.