Biodegradable Magnesium Stent Treatment of Saccular Aneurysms in a Rat Model - Introduction of the Surgical Technique

Summary

Reproducable experimental animal models are needed for the testing of novel embolization materials, which have been designed to treat endovascular occlusion of intracranial aneurysms (IA). The present study aims to develop a safe and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.

Abstract

The steady progess in the armamentarium of techniques available for endovascular treatment of intracranial aneurysms requires affordable and reproducable experimental animal models to test novel embolization materials such as stents and flow diverters. The aim of the present project was to design a safe, fast, and standardized surgical technique for stent assisted embolization of saccular aneurysms in a rat animal model.

Saccular aneurysms were created from an arterial graft from the descending aorta.The aneurysms were microsurgically transplanted through end-to-side anastomosis to the infrarenal abdominal aorta of a syngenic male Wistar rat weighing >500 g. Following aneurysm anastomosis, aneurysm embolization was performed using balloon expandable magnesium stents (2.5 mm x 6 mm). The stent system was retrograde introduced from the lower abdominal aorta using a modified Seldinger technique.

Following a pilot series of 6 animals, a total of 67 rats were operated according to established standard operating procedures. Mean surgery time, mean anastomosis time, and mean suturing time of the artery puncture site were 167 ± 22 min, 26 ± 6 min and 11 ± 5 min, respectively. The mortality rate was 6% (n=4). The morbidity rate was 7.5% (n=5), and in-stent thrombosis was found in 4 cases (n=2 early, n=2 late in stent thrombosis).

The results demonstrate the feasibility of standardized stent occlusion of saccular sidewall aneurysms in rats - with low rates of morbidity and mortality. This stent embolization procedure combines the opportunity to study novel concepts of stent or flow diverter based devices as well as the molecular aspects of healing.

Introduction

Subarachnoid hemorrhage due to a ruptured intracranial aneurysm is associated with a high mortality rate and poor neurological outcome in many survivors. There are currently two general approaches to occlude IA: either microsurgical clipping (which requires operative exposure of the aneurysm), or endovascular occlusion. As the less invasive endovascular coil treatment of narrow-necked IA has been shown to be associated with slightly lower morbidity (especially in the posterior circulation^1,2), endovascular treatment options have become the preferred modality of many neurosurgical centers. Numerous devices have....

Protocol

Male Wistar rats with a mean weight of 592 g (±50 SD) and mean age of 20 weeks were housed in animal facilities at a room temperature of 22-24 °C and twelve hour light/dark cycle, with free access to tap water and a pellet diet. The animals received care from humans in accordance with institutional guidelines. The experiments were approved by the Committee for Animal Care of the Canton Bern, Switzerland (BE 102/13). We strictly followed the recommendations for Animal Research: Reporting of In Vivo Experiments (ARRIVE guidelines).

1. Laboratory equipment, consumable supplies, surgical instruments

1. Use a quiet, a....

Results

The average duration of surgery was 167 (± 22) min, 26 (± 6) min of which were needed for aneurysm creation and a further 23 (± 7) min required for stent application and reconstruction of the arteriotomy (Figure 3).

Mortality, morbidity, and macroscopic in-stent thrombosis were the primary endpoints of the study. The regular follow-up periods were 7 days (n=28), and 21 days (n=32) respectively. Mort.......

Discussion

Bioabsorbable stents and animal models
In recent years the general trend in medicine has been away from permanent implants (which remain in the patient's body for the rest of their life) to bio-absorbable materials. Magnesium stents, in particular, are already quite established in cardiology^8,9. Unfortunately these stents have not yet been tested for other applications, such as cerebrovascular diseases. For this reason we decided to stu.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Medetomidine			any generic
Ketamin			any generic
Buprenorphine			any generic
Phosphate buffered saline
Sodium dodecyl sulfate (0.1%)
3-0 resorbable suture	Ethicon Inc., USA	VCP428G
5-0 non absorbable suture	Ethicon Inc., USA	8618G
6-0 non-absorbable suture	B. Braun, Germany	C0766070
9-0 non-absorbable suture	B. Braun, Germany	G1111140
10-0 non-absorbable suture	Covidien, USA	N2530 Monosof
Operation microscope	Zeiss, Germany
Digital microscope camera	Sony, Japan	HXR-MC1P
Standard surgical instruments		multiple	see protocol 7.a
Microsurgical instruments		multiple	see protocol 7.b
Vascular clip applicator	B. Braun, Germany	FT495T
Temporary vascular clamps	B. Braun, Germany
19G Puncture needle	Angiomed GmbH, Germany	15820010
Hydrophobic guide wire	Cook Medical, USA	G00650
4F sheat	Cordis Corporation, USA	504-604A
Inflation syringe
Laboratory shaker	Stuart	SRT6
Magnesium Stent 2.5/6 AMS with Polymer coating	Biotronik, Switzerland
Surgery drape
Sterile cellulose swabs
Syringes 1 ml and 2 ml
Hollow needles 18G and 26G
Isotonic sodium chloride
Microtubes
Eye ointment	Bausch + Lomb Inc, USA	Lacrinorm	any generic
Small animal shaver