Long-Term Patency of Elastase-Induced Aneurysm Model in Rabbits

Aneurysm Creation

Elastase-induced, saccular aneurysms were created in 20 New Zealand white rabbits (body weight, 3–4 kg) by using the rabbit elastase model. The institutional animal care and use committee at our institution approved all procedures. Detailed procedures for aneurysm creation have been described elsewhere.18 In brief, anesthesia was induced with an intramuscular injection of ketamine, xylazine, and acepromazine (75 mg/kg, 5 mg/kg, and 1 mg/kg, respectively). By using a sterile technique, the right common carotid artery (RCCA) was exposed and ligated distally. A 1–2-mm beveled arteriotomy was made and a 5F vascular sheath (Cordis Endovascular, Miami Lakes, Fla) was advanced retrograde in the RCCA to a point approximately 3 cm cephalad to the origin of RCCA. A roadmap image was obtained by injection of contrast through the sheath retrograde in the RCCA, to identify the junction between the RCCA and the subclavian and brachiocephalic arteries (Advantx; General Electric Company, Milwaukee, Wisc). A 3F Fogarty balloon (Baxter Healthcare Corporation, Irvine, Calif) was advanced through the sheath to the level of the origin of the RCCA with fluoroscopic guidance and was inflated with iodinated contrast material. Porcine elastase (5.23 μ/mgP, 40.1 mgP/mL, approximately 200 U/mL; Worthington Biochemical Corporation, Lakewood, NJ) was incubated within the lumen of the common carotid above the inflated balloon for 20 minutes, after which the catheter, balloon, and sheath were removed, and the RCCA was ligated below the sheath entry site.

Intravenous Digital Subtraction Angiography (IVDSA)

All animals underwent follow-up angiography at each time point (1, 3, 6, 9, 12, and 24 months after creation). All rabbits survived for the full duration of the study. At each time point, as mentioned above, anesthesia was induced as that for creation and a 24-gauge angiocatheter was placed in the left ear vein. Radiopaque sizing markers, consisting of metallic spheres ranging from 2 to 11 mm in diameter, were placed over the chest, as close as possible to the brachiocephalic artery but not obscuring the region of the aneurysm. Technical details can be found as reported elsewhere.17 DSA, at 2 frames per second, was performed with a hand injection of 7 mL of iodinated contrast material (Omnipaque 300, GE Healthcare, Rochester, Minn) into the left ear-vein catheter as quickly as possible. Filming was carried into the arterial phase. Following IVDSA, magnified views of the aneurysm were transferred to film from the IVDSA runs. Animals were allowed to recover for use in further studies.

Image Interpretation

Two experienced observers—an experienced neuroradiologist (D.F.K.) and a trained research fellow (Y.H.D.)—evaluated aneurysm morphology. The IVDSA images for any given subject were viewed separately. Readers were blinded to measurements obtained from the other reading session. To assess intrareader variability, IVDSA images were interpreted twice by both readers. To avoid recall bias, reading sessions were separated by at least 2 weeks.

The width, height, and neck diameters of the aneurysm cavities were determined by employing the external sizing device as a reference. The width of the aneurysm cavity was determined at its point of maximum measurement, while the height was measured from the aneurysm dome to the midportion of a line connecting the proximal and distal portions of the aneurysm neck. Reduction in aneurysm width or height of >1.5 mm was considered evidence of interval partial thrombosis.

Statistical Analysis

Aneurysm sizes (neck, width, and height) were compared within different time points by using the Friedman test. Differences of aneurysm sizes (neck, width, and height) between each time point were compared by using the paired Wilcoxon signed rank test. The differences of the above were evaluated by using an upper 95% confidence limit.

Aneurysm Neck

Mean neck diameters 1, 3, 6, 9, 12, and 24 months after creation were 3.5 ± 0.7 mm, 3.3 ± 0.9 mm, 3.4 ± 0.7 mm, 3.4 ± 0.8 mm, 3.5 ± 0.8 mm, and 3.4 ± 0.8 mm, respectively. There were no significant differences among these neck diameters (P = .210).

Aneurysm Width

Mean aneurysm widths at 1, 3, 6, 9, 12, and 24 months were 3.8 ± 0.8 mm, 3.9 ± 0.9 mm, 4.1 ± 1 mm, 4.0 ± 1.1 mm, 4.1 ± 1.0 mm, and 4.0 ± 0.9 mm, respectively. There were no significant differences among these widths (P = .413).

Aneurysm Height

Mean aneurysm heights at 1, 3, 6, 9, 12, and 24 months after creation were 8.7 ± 1.7 mm, 8.4 ± 1.5 mm, 8.7 ± 2.0 mm, 8.8 ± 1.7 mm, 8.6 ± 1.6 mm, and 8.5 ± 1.7 mm, respectively. There were no significant differences among these heights (P = .405).