Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model

Abstract

Background: The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model.

Methods: The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls.

Results: All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology.

Conclusion: In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

Keywords: AAA inhibition; Abdominal aortic aneurysm; Animal model; Pentagalloyl glucose.

Fig. 1

Notice the significantly lager infrarenal AP-diameter (AP28) in group A (left side) 28 days after surgery compared to the PGG treated group B aorta in the middle (not opened) and control group C (right side). Please note that the shown specimens representing group A and C are specimens from our previous study .

Fig. 2

In group A a progressive aneurysmatic expansion of the infrarenal aortas were seen. After the first postoperative measurement the slope of the increase in AP-diameter in group B and C were a like, indicating that the expansion rate of the AP-diameter in Group B had returned to physiological values, as control group C only showed physiological expansion/growth.

Fig. 3

Histological findings in the three groups. First, second and third column representing group A, B and C respectively (the luminal side to the right). Top row: Verhoeff's stain for elastic tissue enlarged x100. While the elastic lamellae in group A are very dissolved, disorganized, thinned and fragmented, the fibers in group B seem more abundant and organized indicating preserved integrity, especially towards the anti-luminal side in the media. Bottom row: Immunoperoxidase staining for smooth muscle actin enlarged x400 (B2 x100) revealing light to moderate focal muscle atrophy towards the luminal side of the media in group A and B. Group C reveals normal aortic histology in both stains. Please note that the shown specimens representing group A and C are specimens from our previous study .