Serial angiography in an elastase-induced aneurysm model in rabbits: evidence for progressive aneurysm enlargement after creation

Abstract

Background and purpose: Among the several reports of elastase-induced aneurysm models, only the rabbit common carotid artery (CCA) model has been used for testing endovascular occlusion devices. Our purpose was to study the growth characteristics of an elastase-induced aneurysm model in rabbits for the purpose of determining whether delayed aneurysm enlargement occurs after creation.

Methods: Nine New Zealand White rabbits (3-4 kg) were used in this study. All study animals underwent surgery to isolate the right CCA. In three control animals, the lumen was incubated with saline and iodinated contrast material for 20 minutes. In six test animals, the lumen of the CCA was incubated with porcine elastase for 20 minutes. In all study animals, the distal right CCA was ligated. IV digital subtraction angiography was performed on postprocedural days 3, 5, 7, 14, 28, 35, 56, 84, and 112. Using an external sizing reference, the width and height of patent arterial segments at the right CCA origin were measured by two observers. For test animals, aneurysm dimensions were compared between early and late time points by using the Student's t test.

Results: In the control (no elastase) animals, slitlike cavities at the origin of the right CCA decreased in size over time to become nearly obliterated by 21 days. Conversely, a short segment of the proximal CCA remained widely patent in all six test animals. With the exception of a single time point in one test animal, all "aneurysm" cavities in the test animals were dilated as compared with the normal diameter of the CCA. On day 3 after surgery, the mean width and height of the aneurysm cavities in the test animals were 3.2 +/- 0.6 and 6.0 +/- 1.3 mm, respectively. Compared with dimensions at day 3, aneurysms in test animals were larger at day 14, with mean width and height of 4.1 +/- 1.7 and 8.3 +/- 1.9 mm, respectively (P =.02). Aneurysms in test animals had increased further at 21 days compared with 14 days (P =.01). Compared with measurements obtained at 21 days, dimensions remained essentially unchanged at 28 and 35 days. Thirty-five days after surgery, mean width and height were 5.0 +/- 0.9 and 10.0 +/- 2.2 mm, respectively. Follow-up imaging performed < or = 4 months after aneurysm creation showed no further change in aneurysm dimensions.

Conclusion: Elastase incubation and vessel ligation results in patent aneurysmally dilated arterial segments at the origin of the right CCA in rabbits. These aneurysms show progressive increases in diameter over time, finally stabilizing at approximately 1 month. Our data, which show early progressive aneurysm enlargement, suggest that this model may be used for the study of systemic therapies aimed at diminishing aneurysm rest regrowth and also indicate that embolization of these model aneurysms should be delayed at least 21 days after aneurysm creation.

fig 1.

Mean aneurysm width versus time after aneurysm creation. Control animals (no elastase) showed progressive decrease in width over time (open circles). Test animals (elastase injured) showed progressive increase in aneurysm width over time, ≤21 days after aneurysm creation (solid circles). fig 2. Mean aneurysm height versus time after creation. Control (no elastase) animals showed progressive decrease in height over time (open circles). Test animals (elastase injured) showed progressive increase in aneurysm height over time, ≤21 days after aneurysm creation (solid circles). Upper error bars for control animals at 3 and 7 days were removed to avoid confusion.

fig 3.

Angiograms of control animal 3 (no elastase). A, Anteroposterior view IV DSA obtained 3 days after surgery. There is a small, slitlike opening at the stump of the right CCA (straight arrow). B, Anteroposterior view IV DSA obtained 4 weeks after surgery. There has been progressive decrease in the size of the stump of the CCA (curved arrow).

fig 4.

Angiograms of test animal 1. A, Anteroposterior view IV DSA obtained 3 days after creation of aneurysm at origin of right CCA. Brachiocephalic arteries are opacified, including the left CCA (curved arrow), right subclavian artery (open arrow), and “aneurysm cavity” (ie, the aneurysmal dilation of right CCA origin) (straight solid arrows). The aneurysm cavity measures 3.5 mm in width, in reference to the external sizing device. B, Anteroposterior view IV DSA obtained 21 days after creation of aneurysm. The morphology of the aneurysm cavity has changed as compared with that seen on day 3 in that the aneurysm cavity is more bulbous in shape (arrows). The aneurysm cavity measures 5.4 mm in width.

fig 5.

Angiograms of test animal 2. A, Anteroposterior view IV DSA obtained 3 days after creation of aneurysm at origin of right CCA. Brachiocephalic arteries are opacified, including the left CCA (curved arrow), right subclavian artery (open arrow), and aneurysm cavity (straight solid arrows). The aneurysm cavity measures 2.8 mm in width. B, Anteroposterior view IV DSA obtained 17 weeks after creation of aneurysm. The aneurysm cavity measures 4.0 mm in width (arrows).

fig 6.

Angiograms of test animal 4. A, Anteroposterior view IV DSA obtained 3 days after creation of aneurysm at origin of right CCA. Brachiocephalic arteries are opacified, including the left CCA (curved arrow), right subclavian artery (open arrow), and aneurysm cavity (straight solid arrows). The aneurysm cavity measures 4.0 mm in width. B, Anteroposterior view IV DSA obtained 4 months after creation of aneurysm. The aneurysm cavity has markedly enlarged in size as compared with the earlier image, with the aneurysm cavity measuring 6.0 mm in width.