Arterial Pouch Microsurgical Bifurcation Aneurysm Model in the Rabbit

Summary

Developing and testing endovascular devices for intracranial aneurysm treatment is still of great importance. Most aneurysm models used today miss either the important characteristics of an arterial degenerated wall or the hemodynamics of a true bifurcation. Therefore, we aimed to design a novel arterial pouch bifurcation model in rabbits.

Abstract

Endovascular treatment for intracranial aneurysms gained importance over the past decades, consequently there is an increased need of testing endovascular devices. Animal models respecting rheological, hemodynamic and aneurysm wall conditions are highly warranted. Therefore, the aim of the present study was to design a novel standardized and reproducible surgical technique to create autologous arterial pouch bifurcation aneurysms with non-modified and modified wall conditions in rabbits.

Bifurcation aneurysms were created by end-to-side anastomosis of the right on the left common carotid artery, both serving as parent arteries for the arterial pouch, which was microsurgically sewn on. Grafts were taken from the proximal right common carotid artery, either for the control (n = 7, immediate autologous re-implantation) or modified (n = 7, incubated with 100 international units elastase for 20 minutes before autologous re-implantation) group. Pouch and parent artery patency were controlled by fluorescence angiography immediately after creation. At follow-up (28 days), all rabbits underwent contrast enhanced magnetic resonance angiography and fluorescence angiography followed by aneurysm harvesting, macroscopic and histological evaluation.

A total of 16 female New Zealand White rabbits were operated upon. Two animals died prematurely. At follow-up, 85.72% of all aneurysms remained patent. Both groups revealed an increase in aneurysm size over time; this was more pronounced in the control group (6.48 ± 1.81 mm³ at time of creation vs. 19.85 ± 6.40 mm³ at follow-up, p = 0.037) than in the modified group (8.03 ± 1.08 mm³ at time of creation vs. 20.29 ± 6.16 mm³ at follow-up, p = 0.054).

Our findings demonstrate the adequacy of this new rabbit model which allows for the creation of bifurcation aneurysms with different wall conditions in a microsurgical approach. Given the excellent long-term patency and the property of aneurysm growth over time, this model may serve as an important tool for preclinical evaluation of novel endovascular therapies.

Introduction

Subarachnoid hemorrhage resulting from intracranial aneurysm (IA) rupture can effectively be controlled by either endovascular or microsurgical occlusion techniques^1,2,3,4. Different endovascular therapies, to overcome the main limitation of IA recurrence after coiling, gained importance over the past decades generating an increased need of testing endovascular devices. To test these novel treatment approaches, appropriate animal models that respect rheological properties, hemodynamics and aneurysm wall conditions are highly warranted

Protocol

All veterinary care was performed in accordance with the institutional guidelines (all experiments were approved by the Local Committee for Animal Care of the Canton Bern, Switzerland (BE 108/16)) and conducted under supervision of a board-certified veterinarian anesthesiologist. The ARRIVE guidelines and the 3R principles were strictly followed^17,18.

NOTE: House all animals at a room temperature of 22‒24 Celsius (°C) and maintain a 12 hours (h) light/dark cycle. Provide free access to water, pellet and ad libitum hay diet every time. Statistical analyses were perfor....

Results

Following a pilot series of seven animals, totally 16 animals were included in the experimental protocol. Two animals died prematurely and were therefore excluded from the final analysis (12.5% mortality). Calculated on 14 animals, immediate aneurysm patency rate during fluorescence angiography was 71.43% in both, the control and modified group. Four aneurysms had to be reopened with consecutive thrombus evacuation and after a repeated fluorescence angiography there was a documented patency in all cases (100%). Aneurysm .......

Discussion

Our study demonstrates the feasibility of creating a true bifurcation aneurysm model with different wall conditions in rabbits. Overall, 14 female New Zealand White rabbits with a mean weight of 3.7 ± 0.09 kg and mean age of 112 ± 3 days were included in the study. 85.72% of all aneurysms remained patent during a follow-up at 28 days. Two animals died prematurely (12.5% mortality).

Previous studies suggested a variety of extracranial aneurysm models to analyze the management of endov.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
3-0 resorbable suture	Ethicon Inc., USA	VCP428G
4-0 non-absorbable suture	B. Braun, Germany	G0762563
6-0 non-absorbable suture	B. Braun, Germany	C0766070
9-0 non-absorbable suture	B. Braun, Germany	G1111140
Adrenaline	Amino AG	1445419	any generic
Amiodarone	Helvepharm AG	5078567	any generic
Anesthesia machine	Dräger		any other
Aspirin	Sanofi-Aventis (Suisse) SA	622693	any generic
Atropine	Labatec Pharma SA	6577083	any generic
Bandpass filter blue	Thorlabs	FD1B	any other
Bandpass filter green	Thorlabs	FGV9	any other
Bipolar forceps			any other
Bicycle spotlight			any other
Biemer vessel clip (2 x)	B. Braun Medical AG, Aesculap, Switzerland	FD560R	temporary
Bispectral index (neonatal)			any other
Blood pressure cuff (neonatal)			any other
Clamoxyl	GlaxoSmithKline AG	758808	any generic
Dexmedetomidine	Ever Pharma	136740-1	any generic
Electrocardiogram electrodes			any other
Elastase	Sigma Aldrich	45125	any generic
Ephedrine	Amino AG	1435734	any generic
Esmolol	OrPha Swiss GmbH	3284044	any generic
Fentanyl (intravenous use)	Janssen-Cilag AG	98683	any generic
Fentanyl (transdermal)	Mepha Pharma AG	4008286	any generic
Fluoresceine	Curatis AG	5030376	any generic
Fragmin	Pfizer PFE Switzerland GmbH	1906725	any generic
Glyco			any generic
Heating pad			any other
Isotonic sodium chloride solution (0.9%)	Fresenius KABI	336769	any generic
Ketamine	Pfizer	342261	any generic
Laboratory shaker	Stuart	SRT6	any other
Lidocaine	Streuli Pharma AG	747466	any generic
Longuettes			any other
Metacam	Boehringer Ingelheim	P7626406	any generic
Methadone	Streuli Pharma AG	1084546	any generic
Microtubes			any other
Micro needle holder			any other
Midazolam	Accord Healthcare AG	7752484	any generic
Needle holder			any other
O2-Face mask			any other
Operation microscope	Wild Heerbrugg		any other
Papaverine	Bichsel		any generic
Prilocaine-lidocaine creme	Emla		any generic
Propofol	B. Braun Medical AG, Switzerland		any generic
Pulse oxymeter			any generic
Rectal temperature probe (neonatal)			any other
Ropivacaine	Aspen Pharma Schweiz GmbH	1882249	any generic
Scalpell	Swann-Morton	210	any other
Small animal shaver			any other
Smartphone			any other
Soft tissue forceps			any other
Soft tissue spreader			any other
Stainless steel sponge bowls			any other
Sterile micro swabs			any other
Stethoscope			any other
Straight and curved micro-forceps			any other
Straight and curved micro-scissors			any other
Straight and curved forceps			any other
Surgery drape			any other
Surgical scissors			any other
Syringes 1 ml, 2ml and 5 ml			any other
Tris-Buffer	Sigma Aldrich	93302	any generic
Vascular clip applicator	B. Braun, Germany	FT495T
Vein and arterial catheter 22 G			any generic
Vitarubin	Streuli Pharma AG	6847559	any generic
Yasargil titan standard clip (2 x)	B. Braun Medical AG, Aesculap, Switzerland	FT242T	temporary