Swine Models of Aneurysmal Diseases for Training and Research

Summary

Description of two different aneurysmal swine models for neuroradiology training courses and research studies. This study provides evidence of the feasibility of these aneurysm porcine model creations and the reproducible methods that are close to the clinical setting.

Abstract

Large animal models, specifically swine, are widely used to research cardiovascular diseases and therapies, as well as for training purposes. This paper describes two different aneurysmal swine models that may help researchers to study new therapies for aneurysmal diseases. These aneurysmal models are created by surgically adding a pouch of tissue to carotid arteries in swine. When the model is used for research, the pouch must be autologous; for training purposes, a synthetic pouch suffices.

First, the right external jugular vein (EJV) and right common carotid artery (CCA) must be surgically exposed. The EJV is ligated and a vein pouch fashioned from a short segment. This pouch is then sutured to an elliptical arteriotomy performed in the CCA. Animals must be kept heparinized during model creation, and local vasodilators may be used to decrease vasospasms. Once the suture is completed, correct blood flow should be inspected, checking for bleeding from the suture line and vessel patency. Finally, the surgical incision is closed by layers and an angiography performed to image the aneurysmal model.

A simplification of this aneurysmal carotid model that decreases invasiveness and surgical time is the use of a synthetic, rather than venous, pouch. For this purpose, a pouch is tailored in advance with a segment of a polytetrafluoroethylene (PTFE) prosthesis, one end of which is sutured close using polypropylene vascular suture and sterilized prior to surgery. This "sac" is then attached to an arteriotomy performed in the CCA as described.

Although these models do not reproduce many of the physiopathological events related to aneurysm formation, they are hemodynamically similar to the situation found in the clinical setting. Therefore, they can be used for research or training purposes, allowing physicians to learn and practice different endovascular techniques in animal models that are close to the human system.

Introduction

Intracranial aneurysm (IA) is a severe cerebrovascular disease associated with up to a 50% mortality rate when ruptured. It is a relatively common and potentially lethal condition, with a reported prevalence between 3.6% and 6% in angiographic studies¹. The intracranial vessels are abnormally dilated and suffer distension due to multifactorial risk factors, including, but not limited to, smoking, hypertension, excessive alcohol intake, or increasing age. When left untreated, IA can spontaneously rupture, resulting in subarachnoid hemorrhage (SAH) that is responsible for significant morbidity and death^2,

Protocol

The experiment was approved by the ethical committee of the Jesús Usón Minimally Invasive Surgery Centre, and all procedures were performed according to Spanish Royal Decree 53/2013 and the European regulation (2010/63/EC).

1. Presurgical preparation and anesthesia

1. House large white swine weighing 35-40 kg individually, with free access to water and feed once a day. Acclimate for 2 weeks before the date of the intervention, to perform clinical examination and allow time for detecting silent diseases.
2. Administer the following oral drugs to prevent thrombotic events during the study: Acetylsali....

Results

The presented technique has been used for different purposes, namely research into postcoiling aneurysm healing and training in embolization techniques. Venous pouches have been used for testing differential healing using both platinum and bioactive coils. The pouches were sutured as described above and, 24 h after model creation, an angiogram was obtained to document the dimensions and appearance of the aneurysms. Endovascular coil embolization was performed successfully in all the pigs. In each case, the left-side aneu.......

Discussion

There are different techniques to create aneurysm animal models based on the objective of the study. Some aneurysm model protocols include surgical procedures combined with hypertension or hemodynamic stress induction by angiotensin II administration, nephrectomies, or high-salt diet, among others, because the main objective of these studies is aneurysm rupture research. However, in the present study, these conditions are not induced since these animal models are used for neuroradiology training or nonrupture aneurysm re.......

Materials

Name	Company	Catalog Number	Comments
Acetylsalicylic acid	Sanofi	700693	500 mg tablets
Amidotrizoic acid	Bayer Hispania	914614.6	Contrast medium 76%
Anesthesia Machine	Maquet Clinical Care AB	6677200	Maquet Flow-i C20
Bulldog vascular clamp	Dimeda	12.092.07	7.5 cm
Buprenorphine	Richter Pharma Ag	578816	0.3 mg/mL
Clopidogrel	Sandoz	704005	75 mg tablets
Contrast medium	Bayer Hispania	914614	Urografin 36%
Dissector	Dimeda	12.421.01	21 cm
Fentanyl Matrix	Kern Pharma	664823	Transdermic release patch 25 µg/h
Fluoroscopy equipment	Philips Medical Systems		Veradius Unity
Hemostatic gelatin sponge	Takeda Farmaceutica España, SA	324459	Absorbable hemostatic agent. Espongostan
Head hunter catheter	Boston Scientific	RF*YB15110M	5 Fr 100 cm
Heparin	Rovi	641639	Heparin 5%
Hydrophilic guidewire	Terumo	RF*GA35153M	0.035” 150 cm
Introducer sheath	Terumo	RS*B60N10MQ	6 Fr 10 cm
Ketamine	Richter Pharma Ag	580395	100 mg/mL
Ketorolac	Laboratorios Normon, S.A.	603079	30 mg/mL
Micro-forceps	S&T	JFA-5b (1:1)	Forceps for microsugery
Micro-needle holder	S&T	Curved C-14 (Art nº 00088)	Needle holder for microsurgery
Microscissors	S&T	Adventitia SAS-15 R-8 (Art nº 00102)	Straight- scissors for microsurgery
Needle holder	Dimeda	24.114.12	12 cm
Nimodipine	Bayer Hispania, S.L	641969	10 mg/50 mL
Povidone-iodine	CV Medica	193203	Povidone iodine solution (10%)
Propofol	Orion Corporation	588475	10 mg/mL
PTFE prosthesis	Maquet	M00201501086B0	Synthetic prosthesis 6mm
Remifentanil	Laboratorios Normon, S.A.	692295	2 mg
Scalpel handle	Dimeda	06.104.00	13.5 cm
Scissors (Mayo)	Dimeda	07.164.14	14.5 cm
Scissors  (Metzenbaum)	Dimeda	07.287.15	15 cm
Surgical blades	Dimeda	06.122.00	22
Sutures: absorbable suture	Medtronic	GL-123	2/0
Sutures: poplypropylene suture	Aragó	37803	6/0 and 7/0
Swabs	Texpol	1063.01	20 x 20 cm
Tissue forceps	Dimeda	10.102.11 /10.120.11	11.5 cm
Vascular glue	Histoacryl Braun	1050060	Tissue adhesive
Vessel loops	Braun	B1095218	1.5 mm diammeter
Weitlaner	Dimeda	18.670.14	14 cm