Neurological deficits associated with the elastase-induced aneurysm model in rabbits

Abstract

Objective: Although the rabbit elastase-induced aneurysm model is currently used widely for endovascular research and device testing, procedural causes leading to animal morbidity and mortality have not yet been clearly described. We conducted a retrospective study to analyse factors contributing to neurological deficits in rabbits that underwent the elastase-induced aneurysm creation procedure at our research center from 2002 to 2005 in order to improve the technique and reduce procedure-related morbidity and mortality.Methods: A total sample of 38 animals that underwent the procedure under the same conditions was analysed in two groups: animals that presented neurological deficits (ND, n=15) and animals that were neurological deficit free (NDF, n=23). Data were collected by reviewing the animal records and radiographic images from the procedures. Statistical analyses using the Mann-Whitney test, unpaired t-test with Welch correction and Fisher's exact tests were performed to compare the two groups based on variables associated with endothelial injury and activation of the coagulation cascade. Results:The variables of animal weight (signifying state of health of the animal), total procedure time, total balloon occlusion time and clot formation were found to be significantly and/or very significantly correlated to ND presentation.Discussion: Successful creation of the rabbit elastase-induced aneurysm model depends on careful control over several technical details. Important variables governing outcome have been identified here. A specific, improved endovascular arrangement that facilitates maneuvering of the devices and reduces the risk of air emboli is presented.

A modified method of elastase-induced saccular aneurysm creation in rabbits: Schematic representation of the method

“…20 Conversely, the short endovascular procedure time of <25 min was shown to minimize complications in the rabbits. 12,14,21 Our experimental group with a relatively short procedure time of 23 ± 2 min suggests a safe model without neurologic deficits. The body weight changes of an experimental animal have been known well to be an important indicator of experimental success.…”

“…To minimize air embolism or prevent elastase leakage, Liliana et al suggested that the intervention protocol used in this clinical trial could be applied to animal experiments. 12 However, the presented method was a design that was not applied to an actual experiment, and the materials used were several and complicated, which may cause inconvenience to the operator. The procedure of the control group was relatively simpler; however, a phenomenon that elastase was leaked through the robber hub with the hemostatic valve part of the sheath was indicated.…”

“…Elastase was subsequently infused into the isolated RCCA segment via a coaxially-introduced microcatheter. [10][11][12] The rabbit aneurysm model using this method is known as a reliable and well-established method.…”

“…A prolonged inflation of the balloon and leakage of elastase had been identified as a major factor influencing the success or failure of rabbit endovascular elastase-induced aneurysm creation in a previously published study. [12][13][14] We needed an increasingly reliable and safe method and set-up materials that could exclude the influence of the operator's ability as much as possible from the conventional methods. Therefore, we created a modified technique of using a short guiding catheter to increase the safety of endovascular interventions for the creation of saccular aneurysms.…”

Endoluminal Scaffolds for Vascular Reconstruction and Exclusion of Aneurysms From the Cerebral Circulation

“…We constructed elastase-induced aneurysms in rabbits [5,6] and implanted three different ESVRs. The devices selected were two that scored the best (devices C and E, Figure 3) and device B that had the same porosity but different pore density than device E. Twenty one (n=9), 90 (n=9) & 180 days (n=12) post-implantation, the aneurysms were evaluated by angiography, the animals were sacrificed, and the vasculatures containing the implants were harvested for histological evaluation.…”