Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease

<div><p>The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.</p></div

Follow-up of aortic diameter by IVDSA.

<p>Aneurysm and proximal stenosis was obvious in Group A after 3 weeks (a). Aneurysm enlarged further and stenosis disappeared in Group A after 15 weeks (b). (c) Profile of diameter changes indicated that Aneurysm groups dilated progressively, but diameter enlargement in Group A was significantly lower than in Group B at 7 weeks. *** <i>p</i> < 0.0001, Group B compared with Group A and SHAM group; +++ <i>p</i> < 0.0001, Group A compared with SHAM group.</p

Profiles of elatin content change by EVG staining.

<p>Elastin fibers were destroyed markedly by week 1, and elastin increased progressively thereafter. **<i>p</i> < 0.01, ***<i>p</i> < 0.0001. Original magnification ×400.</p

Profiles of aortic lumen perimeters.

<p>Media thickness increased significantly by week 15 in Group A (a); Intimal hyperplasia increased significantly by week 7 in the Aneurysm groups. Group A increased significantly by week 15 compared with Group B. (b); IMT increased significantly by week 7 in Group A (c); IMR increased significantly by week 15 in the Aneurysm groups (d). * <i>p</i> < 0.05, ** <i>p</i> < 0.01, *** <i>p</i> < 0.0001. IMR = intima-media ratio; IMT = intima-media thickness.</p

Smooth muscle cells changes and the profiles of content change.

<p>SMCs were destroyed markedly after 1 week, but increased progressively thereafter. SMCs content in Group A increased significantly by week 15 compared with Group B. **<i>p</i> < 0.01, ***<i>p</i> < 0.0001. Original magnification ×400.</p

Additional file 1 of Covered SEMS failed to cure airway fistula closed by an amplatzer device

Supplementary Material

The preoperative color Doppler flow imaging.

<p>CDUS shows a membranous obstruction of IVC wiht thin beam-like flow (Figure 1 a), and the right HV is completely obstructed (Figure 1 b); There is a obliteration after the confluence of left HVs without blood flows (Figure 1 c), the right HV has compensatory enlargement, with blood flow draining into IVC (Figure 1 d).</p

The CTA images of portal venous phase and DSA image during intervention.

<p>The middle HV is obstructed, the right and left HVs are completely obstructed (Figure 4 a); The right, rear and inferior HVs are expanded (Figure 4 b), and the segmental IVC is obstructed (Figure 4 c); DSA image shows a segmental obstruction of the inferior caval vein, and intrahepatic collateral circulation for drainage of HV flows (Figure 4 d).</p

The inferior venocavography through the femoral access.

<p>The IVC is obstructed at the secondary porta of liver, and the adopted contrast agent is thin and beam-like (Figure 3 a), the right and rear HVs are remarkably dilated (Figure 3 b).</p

MRI axial and 3D reconstruction images for showing HVs and IVC.

<p>The right HV is completely obstructed and the middle and left HVs are obstructed after their confluence (Figure 2 a). The IVC shows a membranous stenosis, and the right HV is compensatory enlarged (Figure 2 b).</p