Porcine Model of Infrarenal Abdominal Aortic Aneurysm

Summary

This novel model creates robust infrarenal abdominal aortic aneurysms in swine using a combination of balloon angioplasty, elastase/collagenase perfusion, topical elastase application, and oral compound β-aminopropionitrile administration, which interferes with collagen cross-linking.

Abstract

Large animal models to study abdominal aortic aneurysms are sparse. The purpose of this model is to create reproducible, clinically significant infrarenal abdominal aortic aneurysms (AAA) in swine. To achieve this, we use a combination of balloon angioplasty, elastase and collagenase, and a lysyl oxidase inhibitor, called β-aminopropionitrile (BAPN), to create clinically significant infrarenal aortic aneurysms, analogous to human disease.

Noncastrated male swine are fed BAPN for 7 days prior to surgery to achieve a steady state in the blood. A midline laparotomy is performed and the infrarenal aorta is circumferentially dissected. An initial measurement is recorded prior to aneurysm induction with a combination of balloon angioplasty, elastase (500 units)/collagenase (8000 units) perfusion, and topical elastase application. Swine are fed BAPN daily until terminal procedure on either postoperative day 7, 14, or 28, at which time the aneurysm is measured, and tissue procured. BAPN + surgery pigs are compared to pigs that underwent surgery alone.

Swine treated with BAPN and surgery had a mean aortic dilation of 89.9% ± 47.4% at day 7, 105.4% ± 58.1% at day 14, and 113.5% ± 30.2% at day 28. Pigs treated with surgery alone had significantly smaller aneurysms compared to BAPN + surgery animals at day 28 (p < 0.0003). The BAPN + surgery group had macroscopic and immunohistochemical evidence of end stage aneurysmal disease.

Clinically significant infrarenal AAA can be induced using balloon angioplasty, elastase/collagenase perfusion and topical application, supplemented with oral BAPN. This model creates large, clinically significant AAA with hallmarks of human disease. This has important implications for the elucidation of AAA pathogenesis and testing of novel therapies and devices for the treatment of AAA. Limitations of the model include variation in BAPN ingested by swine, quality of elastase perfusion, and cost of BAPN. 

Introduction

According to the Center for Disease Control (CDC), aortic aneurysms (AA) are a leading cause of death in the United States and represent a significant disease burden¹. An aortic aneurysm is defined as a dilation of a discrete portion of the vessel lumen by over 50%². A subset of AA in the abdomen, referred to as abdominal aortic aneurysms (AAA) are a growing concern. AAA remain clinically silent until impending rupture or dissection, with acute onset, severe abdominal pain generally being the only presenting symptom^3,4. Rupture of AAA is almost always fatal with ....

Protocol

Animal protocols were approved by the University of Virginia Institutional Animal Care and Use Committee (No. 3848).

NOTE: This model has been previously published by Cullen et al. and is a modified protocol described by Hynecek et al.^8,15.

1. Animals

1. Use non-castrated male swine weighing 20-30 kg for the experiments.
2. In order to maximize the proportion of weight-based doses of BAPN ingested, provide pigs with divided meals of standard chow and 0.15 g/kg of BAPN mixed with whole-milk plain yogurt or wet dog food. Start BAPN admi....

Results

All statistical analyses were performed using Fisher exact test or chi squared test as appropriate. Data values are reported as mean aortic dilation (%) ± standard deviation (%). Statistical significance was set P < 0.05. The combination of BAPN and surgery providing elastase treatment (surgery/elastase) creates more robust and reproducible AAA in swine at day 28 compared to those treated with surgery and elastase alone (mean aortic dilation (%) ± standard deviation (%): 113.5% ± 30.2% (n = 8) versus 5.......

Discussion

A novel model of infrarenal AAA in swine was created using a combination of balloon angioplasty, perfusion and topical elastase, and dietary as BAPN. Using this model, aortic dilation of >100% was achieved with gross and histologic characteristics of chronic human aneurysmal disease. This model provides a gateway to further understand the complex pathophysiology of AAA and translate potential therapies to human disease.

Prior models of AAA in swine have been achieved with modest success. M.......

Materials

Name	Company	Catalog Number	Comments
Arrow Ergo Pack System	Arrow	CDC-21242-X1A	Just need 7 Fr dilator
Atlas PTA Balloon dilation catheter	Bard	AT-120184	16 mm x 4 cm x 120 cm
Bovie electrocautery	Bovie Medical	A2350
Collagenase Type 1 (5 gm)	Worthington	LS004196
Crile Needle drviers	MFI medical	61-2201
DeBakey Atraumatic Forceps	MFI medical	52-4977
DeBakey Peripheral Vascular Clamp	Medline	MDS1318119
Glidewire	Terumo Interventional Systems	GS3506	outer Wire diameter 0.035 mm, Length 150 cm
GraphPad Prism 6	GraphPad Software Inc. La Jolla, Calif)		statistical software
Metzenbaum Scissors	MFI medical	61-0004
Mayo-Hegar Needle Holder	tiger medical	N407322
Micropuncture Introducer Set	Cook	G47946
Mixter Forceps, Standard Grade, Right angle	Cole-Parmer	UX-10818-16
Monocryl suture	Ethicon	Y496G-BX	4-0 monocryl
PDS II suture	Ethicon	D8926	Number 1 looped
Porcine Pancreatic Elastase	Sigma-Aldrich	E1250
Satinsky Vascular Clamps	Medline	MDs5632515
Suction canister	Cardinal Health	65651212
Schuco Aspirator	MFI medical	S430A
Vicryl suture	Ethicon	J789D-SD	2-0 vicryl
Yankauer Suction tube	Sklarcorp	07-1801