Research Article: Hemodynamics and pathology of an enlarging abdominal aortic aneurysm model in rabbits

Date Published: October 12, 2018

Publisher: Public Library of Science

Author(s): Hongmei Chen, Yonghua Bi, Siyeong Ju, Linxia Gu, Xiaoyan Zhu, Xinwei Han, Michael Bader.

http://doi.org/10.1371/journal.pone.0205366

Abstract

Hemodynamics may play an essential role in the initiation and progression of abdominal aortic aneurysm (AAA). We aimed to study the mechanism of self-healing process by the changes of hemodynamics and pathology in an enlarging AAA in rabbits. Seventy-two rabbits were randomly divided into three groups. Rabbits underwent extrinsic coarctation and received a 10-minute elastase incubation in Group A and Group B. Absorbable suture used in Group A was terminated by balloon dilation at week 4. Diameter was measured after 1, 3, 5, and 15 weeks, computational fluid dynamics analysis was performed at week 3 and week 15. Rabbits were sacrificed after 1, 5, and 15 weeks for pathological and quantitative studies. The higher velocity magnitude, intensified bulk flow and obvious vortex formation were observed in Group A at week 3 instead of week 15. Both low wall shear stress and high relative residence time increased in Group B, however, high oscillatory shear index had relatively less increase compared with Group A. Aortic diameter reached a plateau at 5 weeks in Group A, which was significantly lower than in week 15 in Group B. Intimal hyperplasia, intima-media thickness increased significantly in Group A at week 5, significantly higher than in week 15 in Group B. Marked destruction of elastin fibers and smooth muscle cells occurred at week 1, and increased significantly at week 15 in Group A. Aneurysm exhibited strong expression of matrix metalloproteinase 9 and mouse anti-rabbit macrophage 11 at week 1, and showed a tendency to decrease. Matrix metalloproteinase 2 expression decreased significantly in Group B at week 15 compared with week 5 and Group A. In conclusion, the self-healing of rabbit AAA may attributed to the regeneration of smooth muscle cells. The turbulence flow caused by coarctation is associated with continuous growth of rabbit AAA and prevents the self-healing phenomenon.

Partial Text

Abdominal aortic aneurysm (AAA) is characterized by chronic remodeling of aortic wall tissue, however, its pathogenesis remains poorly understood. [1] Animal models have been developed to mimic human AAA disease, [2] which included genetically predisposed AAA model, chemical injury AAA model, and hemodynamically-induced AAA model. Although the chemical injury AAA model has been popular used in animal studies, [3–9] this model does not always induce stable AAA. [10–12] It has been reported that elastase-induced AAA in rabbit heals spontaneously. [8] This performance is quite different from human AAA. Thus, the enlarging AAA models have been successfully induced to overcome the self-healing phenomenon. [4, 13] The different outcomes of elastase-induced AAA and an enlarging AAA indicated that hemodynamic change may play an essential role in the initiation and progression AAA in rabbits. In the current study, we aimed to study the mechanism of self-healing process by the changes of hemodynamics and pathology in an enlarging AAA in rabbits.

The chemical injury AAA model has been popular used in animal studies. [3–9] Rabbit AAA did not form after 30-min incubation with low concentration elastase solution (0.1–5 units/μl), [3] until aorta destroyed significantly via high concentration elastase. [4] However, elastase induction does not always induce stable AAA and may returned to normal condition soon, [10] namely self-healing phenomenon. [8], To overcome this phenomenon, new kinds of enlarging AAA models were induced in rabbits and rats. [4,13]

 

Source:

http://doi.org/10.1371/journal.pone.0205366

 

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