Trans-Iliac Rat Aorta Stenting: A Novel High Throughput Preclinical Stent Model for Restenosis and Thrombosis

Oyamada, Shizu; Ma, Xiaodong; Wu, Tingting; Robich, Michael P.; Wu, Hao; Wang, Xingwei; Buchholz, Bryan; McCarthy, Stephen P.; Bianchi, C; Sellke, Frank W.; Laham, Roger J.

doi:10.1016/j.jss.2010.11.882

Cited by 9 publications

(10 citation statements)

References 12 publications

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“…AAo stenting was performed under anesthesia and sterile conditions (12,36). Local BF patterns and the subsequent severity of NH are influenced by stent geometry (29).…”

Section: Methodsmentioning

confidence: 99%

Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

Wang

Weihrauch

Kersten

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Mechanisms of restenosis in type 2 diabetes mellitus (T2DM) are incompletely elucidated, but advanced glycation end-product (AGE)-induced vascular remodeling likely contributes. We tested the hypothesis that AGE-related collagen cross-linking (ARCC) leads to increased downstream vascular resistance and altered in-stent hemodynamics, thereby promoting neointimal hyperplasia (NH) in T2DM. We proposed that decreasing ARCC with ALT-711 (Alagebrium) would mitigate this response. Abdominal aortic stents were implanted in Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. Blood flow, vessel diameter, and wall shear stress (WSS) were calculated after 21 days, and NH was quantified. Arterial segments (aorta, carotid, iliac, femoral, and arterioles) were harvested to detect ARCC and protein expression, including transforming growth factor-β (TGF-β) and receptor for AGEs (RAGE). Downstream resistance was elevated (60%), whereas flow and WSS were significantly decreased (44% and 56%) in ZD vs. ZL rats. NH was increased in ZO but not ZD rats. ALT-711 reduced ARCC and resistance (46%) in ZD rats while decreasing NH and producing similar in-stent WSS across groups. No consistent differences in RAGE or TGF-β expression were observed in arterial segments. ALT-711 modified lectin-type oxidized LDL receptor 1 but not RAGE expression by cells on decellularized matrices. In conclusion, ALT-711 decreased ARCC, increased in-stent flow rate, and reduced NH in ZO and ZD rats through RAGE-independent pathways. The study supports an important role for AGE-induced remodeling within and downstream of stent implantation to promote enhanced NH in T2DM.

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“…AAo stenting was performed under anesthesia and sterile conditions (12,36). Local BF patterns and the subsequent severity of NH are influenced by stent geometry (29).…”

Section: Methodsmentioning

confidence: 99%

Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

Wang

Weihrauch

Kersten

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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“…The small peripheral vasculature diameter of a medium sized rat makes trans-carotid and trans-iliac endovascular device deployment difficult 5,6 . However, devices can also be placed through direct abdominal aortic insertion or direct placement into the experimental aneurysm before end-tosite anastomosis 7,16 .…”

Section: Discussionmentioning

confidence: 99%

“…Murine aneurysm models, on the other hand, allow testing research questions in genetically modified species 3,4 and facilitate clarification of aneurysm biology at cellular and molecular level far better than larger species 1 . Although endovascular trans-carotid and trans-iliac device deployment is limited to bigger rats (>400-500 g) and stents smaller than 2.0 mm and 1.5 mm in diameter 5,6 , stents can also be placed through direct insertion into the abdominal aortic segment harbouring the experimental aneurysms. Previous work using the rat microsurgical abdominal aortic sidewall aneurysm model demonstrated its feasibility in testing novel embolic devices and its use in studying the molecular basis of aneurysm biology 3,7 .…”

Section: Introductionmentioning

confidence: 99%

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

Marbacher

Marjamaa

Abdelhameed

et al. 2014

JoVE

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Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms.Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions.The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta.We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. Video LinkThe video component of this article can be found at

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“…Previous studies have shown high rates of mortality in abdominal stent implantation. The values vary from 5.7 -57% 12,13,14,15 . Most animals died of thrombosis following the intima injury during stent implantation 16 .…”

Section: Morbidity and Mortalitymentioning

confidence: 99%

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

Nevzati

Rey

Coluccia

et al. 2017

JoVE

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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.

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Trans-Iliac Rat Aorta Stenting: A Novel High Throughput Preclinical Stent Model for Restenosis and Thrombosis

Abstract: Background-Currently, preclinical stent development requires elaborate large animal models which are time consuming and expensive. We herein report a high throughput rat aorta stenting model which could provide a rapid and low-cost platform for preclinical stent development.

Cited by 9 publications

References 12 publications

Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

The Helsinki Rat Microsurgical Sidewall Aneurysm Model

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

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