Complications of Elastase-Induced Arterial Saccular Aneurysm in Rabbits: Case Reports and Literature Review

Endoluminal infusion and incubation of elastase with or without collagenase into the rabbit common carotid artery is an established model of arterial saccular aneurysm. The model mimics naturally occurring human cerebral aneurysms in many ways, including histologic and morphologic characteristics, hemodynamic pressures, and shear stresses. However, complications have been associated with the model. Here, we report 2 complications: 1) the first known case of iatrogenic laryngeal hemiplegia in a rabbit; and 2) histopathologically confirmed iatrogenic hippocampal and cerebellar infarcts (stroke). Finally, we present and review data from current literature on the morbidity and mortality associated with this model.Abbreviations: CCA, common carotid artery; RLN, recurrent laryngeal nerveElastase-induced aneurysm in the rabbit common carotid artery (CCA) is an established model of arterial saccular aneurysm^2,6 that provides an alternative to large animal (for example, swine and canine) models of saccular aneurysm. The degradation of the elastic lamina with elastase leads to a cascade of changes in extracellular matrix proteins and progressive inflammatory infiltration as seen in naturally occurring cerebral and aortic aneurysms.¹⁵ These changes lead to thin-walled aneurysms⁹ that are morphometrically²⁸ and histologically¹ similar to naturally occurring human cerebral aneurysms. In addition, the created aneurysms have hemodynamic pressures and shear stresses similar to those of human cerebral aneurysms,²⁴ because the rabbit''s carotid artery is also comparable in size to human middle cerebral arteries.¹ Rabbits also have comparable thrombotic and thrombolytic profiles to those of humans.¹⁶Despite the advantages, this rabbit model has limitations. These include the inability to control the size of aneurysms (potentially corrected by adjusting the ligation site);¹⁰ sacrifice of the arterial access for each angiogram;⁴ absence of clear atherosclerotic changes, thus limiting data extrapolation to the “true human degenerative aneurysm”;²⁷ and small size of rabbits, thus limiting the evaluation of large devices or techniques requiring multiple catheters.¹³ In addition, rare spontaneous ruptures of elastase-induced aneurysms have been reported;^1,6,17,19 these ruptures were postulated to be due to residual collagen in the vessel wall, given that collagen is important to maintain the wall''s tensile strength.³³ Therefore, the natural history of human intracranial aneurysm is not precisely produced in this rabbit model. Because alterations in either the quantity^14,26,30 or quality³² of collagen may be related to the development of cerebral aneurysms in humans, the traditional technique for creating these aneurysms in rabbits was modified to include the infusion and incubation of collagenase into the CCA.Creating the model involves careful dissection of the ventral neck region to isolate the CCA and infuse it with elastase with or without collagenase. Complications arising from this technique have been reported. Here, we present 2 clinical cases based on our experience: the first known case of iatrogenic laryngeal hemiplegia in a rabbit and a histopathologically confirmed case of iatrogenic rabbit stroke. We also review the literature regarding complications associated with creating this model.