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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.
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.
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 death2,3,4. Additionally, one third of patients require hospitalization or nursing care, and only 30% of patients with SAH can return to independent living, thus representing a serious disease burden in humans that actually justifies the need for animal experiments5.
Nowadays, patients with high risk of IA rupture and hemorrhage are treated with occlusion mainly by endovascular coiling, microsurgical clipping, or flow diverting stents6,7. The endovascular procedure has been evaluated by the International Subarachnoid Aneurysm Trial (ISAT), demonstrating that coiling is safer, less invasive, and therefore has less significant adverse effects than microsurgical therapy3. For these reasons, the endovascular procedures are the most common techniques used for IA treatment3. Specialized training is required for physicians to perform these minimally invasive procedures correctly8.
Moreover, the development of new devices or therapies for IA treatment needs to be well-established and tested in preclinical studies before their translation to the clinical setting6,9. There are different IA experimental animal models according to the main objective of the research or training purposes. These models have been performed in numerous species, with their limitations and advantages. However, all of them entail artificial induction or surgical creation due to the absence of natural IA in animals2,6,9,10,11,12.
Although no animal model perfectly reproduces the human pathophysiology, small animals, such as rodents, are the most frequently used in IA research studies6. Large species are usually employed for the development of new endovascular devices or training in therapeutic interventions2. Among large animal models, it is common to use swine to research IA disorders and therapies, as well as for training courses. This is because of their ability to tolerate the surgical procedure and their similar vascular diameter and blood flow when compared to human cerebral vessels2,13.
The method of choice for IA animal model creation varies depending on the main objective of each individual research project, such as whether angiographic or histologic endpoints will be evaluated. In this sense, models created by surgical ligation or by adding an autologous pouch of tissue to the CCA are used for IA growth research. Surgical models must be combined with hypertension induction if the primary endpoint of the study is IA rupture. When the model is used for training purposes, the technique can be simplified by using a synthetic pouch sutured onto the CCA without the need for hypertension6.
This paper describes two different aneurysmal swine models that may help researchers to study new therapies or training in endovascular interventions for IA diseases. These aneurysmal models are created by surgically adding a pouch of tissue to the CCA in swine. When the model is used for research, the pouch is autologous, thus providing the ability to study healing of the aneurysm after exclusion without the interference of any exogenous material. For training purposes, a synthetic pouch that recapitulates the endovascular anatomy to reproduce the procedure suffices.
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
2. Surgery
3. Angiography test and postoperative phase
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...
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...
The authors have no conflicts of interest to disclose.
The study was performed by the ICTS 'NANBIOSIS', more specifically by U-21 (Experimental Operating Rooms), U-22 (Animal Housing), and U-24 (Medical imaging) of the Jesús Usón Minimally Invasive Surgery Centre (JUMISC). This work was funded by the Instituto de Salud Carlos III (CB16/11/00494) and the Consejeria de Economía, Ciencia y Agenda Digital, Junta de Extremadura (GR21201), cofunded by the European Regional Development Fund "A way to make Europe". The authors acknowledge all the work performed by the animal housing, experimental technicians, and Joaquín González for taking photos of the surgical procedure.
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 |
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