A New Murine Model of Endovascular Aortic Aneurysm Repair
July 7th, 2013
Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.
Hello, I'm Dr.We we are at the cardiovascular Research Department in Beha Hospital. The following sequences will show you the different steps to induce and then to treat an abdominal arctic aneurysm in rat rat abdominal aneurysm. Induction with elatta has been described by nature in 1990.
In this laboratory, the same year par published the first cases of endovascular abdominal aneurysm repair In humans, we present the first endovascular exclusion after triple A induced by elatta in rats with a coronary covered balloon expendable and graft, A short isof fluorine anesthesia, followed by a panus pen. Barbital intraperitoneal injection induces a long anesthesia time. Skin is shaved then disinfected after op pubic incision.
Internal organs are placed in a wet compress in the left side of the animal. The peritoneum is not torn but smoothly cut to reduce adhesions, which may make the second step of the procedure more difficult. All the collaterals are ligated at the origin of the ata with a nine zero proline, the dissection should be as minimal as possible to reduce the risk of adhesions between the ATA and inferior vena cava.
When all the collaterals are ligated, a double loop silk is wrapped around the aorta, 15 millimeters below the left renal vein. Aorta must be fully dissected below the left renal vein and above the aortic bifurcation to allow self clamping aorta is clamped. Adventitia is removed at the place of the AOR autotomy for a clean stitching.
At the end of the procedure, a small AOR autotomy is performed. Blood is flushed from the aorta to prevent clot formation, which could embolize. When DEC clamping catheter is inserted until the proximal clamp, the silk is tightened to prevent catheter expulsion with the high or aortic pressure During injection.
When injection begins, the aortic diameter rapidly increases. It is important to maintain wall tension for optimal elastase infusion. At the end of the infusion, aortic wall is almost transparent and the catheter is visible reflecting a good diffusion of the elastase in the aortic wall.
When the infusion is finished, the silk is cut, aorta flush with saline and aorta. Autotomy is closed with a 10 zero proline after clamp removal. Adequate hemostasis is insured with manual pressure using a wet pack.
Rat abdominal wall is sutured with a continuous suture and the ceiling enclosed with interruptive sutures. Before the end of the anesthesia, a subcutaneous injection of carprofen is given to prevent pain. Inflator is used to deploy the stent at eight atmosphere pressures.
A silk or braided non-absorbable suture is used to clamp the aorta. We use at least three a traumatic clamps. We deploy the balloon expandable coronary stent graft with a diameter of three millimeters and the length of nine to 16 millimeters after as if of pubic incision Care should be triggered to avoid internal organs, which may be stuck to the wall from adhesions.
The aneurysm is expected to be close to the left renal vein. It's important to leave a long segment of normal aorta below the aneurysm when clamping to allow an easy stent graft insertion, and also to aid the closure of the atomy. Proximal neck is controlled with a double loopt suture and just proximal to the OR bifurcation stent graft choice depends on the aneurysm size.
Proximal and distal ceiling zones should be about two to three millimeters. Here we use a 12 millimeter stent. Graft aorta is clamped approximately and distally.
A large atomy is performed. The aorta isn't flushed. To maintain the position of the aneurysm thrombus, the stent graft is directly inserted.
When the shaft is stopped by the clamp, the suture is tightened around the aorta and the clamp removed. Suture tension allows progression of the stent through the aortic lumen. Until satisfactory position is achieved, the balloon is inflated at eight atmosphere pressures then deflated while tightening.
The proximal loop, blood is flushed from the stent graft. Then a clamp is placed just above the aneurysm to allow a careful aortic closure After fixation in glutaraldehyde and a resin block. HPS stain reveals mesenchymal cells outside the PTFE graft.
This demonstrates a regeneration process within the thrombus. The main limitation is the high frequency of vessel occlusion. Both the stent graft and aorta thrombose easily possibly due to interval injuries during stent graft insertion, and clots within the stent.Graft.
After deployment, aspirin, administration to the rats after the operation may prevent thrombus formation. This model of endovascular exclusion of an aortic aneurysm is the first to be described in the small animal. It'll have been of great help for improving the understanding of aneurysm remodeling in the excluded sac.
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Overview
This study presents a novel model for endograft implantation on a murine aneurysm to elucidate histological and biochemical changes following aneurysm endograft exclusion. The model facilitates thrombus analysis and evaluation of new endovascular biomaterials, contributing to the understanding of endovascular aneurysm exclusion pathobiology.
Key Study Components
Area of Science
- Cardiovascular research
- Endovascular procedures
- Animal models
Background
- Aneurysm endograft exclusion is not fully understood.
- Previous studies have focused on human cases of endovascular abdominal aneurysm repair.
- There is a need for improved models to study aneurysm pathobiology.
- Thrombus analysis is crucial for understanding the effects of endografts.
Purpose of Study
- To develop a murine model for studying endograft implantation.
- To analyze thrombus formation with varying blood stream interfaces.
- To evaluate new endovascular biomaterials.
Methods Used
- Induction of abdominal aortic aneurysm in rats using elatta.
- Endovascular exclusion performed with a covered balloon expandable graft.
- Use of isoflurane anesthesia for surgical procedures.
- Intraperitoneal injection of barbital for prolonged anesthesia.
Main Results
- Successful induction of abdominal aortic aneurysm in the rat model.
- Demonstration of endovascular exclusion techniques.
- Analysis of thrombus formation under different conditions.
- Evaluation of the performance of new endovascular biomaterials.
Conclusions
- The developed model provides insights into aneurysm endograft exclusion.
- Findings may enhance understanding of thrombus dynamics.
- This research could inform future endovascular treatment strategies.
Frequently Asked Questions
Executive Industry Relevance
This model addresses a critical gap in preclinical cardiovascular research by providing a reproducible rat-based system for studying endovascular aneurysm exclusion. It enables mechanistic investigation of thrombus dynamics and biomaterial-tissue interactions post-exclusion, supporting de-risking of novel endovascular devices. The model enhances predictive confidence in preclinical evaluation by replicating key pathophysiological features of human AAA, including inflammatory infiltration and luminal thrombus formation.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of thrombus formation pathways and inflammatory responses in the aneurysm sac post-exclusion.
- Operational Value: Provides a standardized platform for validating biological targets involved in aneurysm remodeling and thrombosis.
Screening & Assay Development
- Scientific Value: Supports development of assays to quantify thrombus characteristics and endothelial responses to stent grafts.
- Operational Value: Facilitates reproducible testing of endovascular biomaterials under controlled hemodynamic conditions.
Translational & Preclinical Research
- Scientific Value: Models human AAA pathophysiology, including elastin degradation and thrombus formation, enabling translational biomarker discovery.
- Operational Value: Supports preclinical continuity from aneurysm induction to endograft exclusion, improving risk-adjusted advancement decisions.
Pipeline & Workflow Integration
The model fits within the discovery continuum from target validation through lead identification to preclinical evaluation, specifically enabling assessment of device-biomaterial interactions in a disease-relevant system.
- Discovery Biology: Supports hypothesis testing on thrombus biology and endothelial responses following endograft deployment.
- Screening: Enables assay-ready systems for evaluating stent graft patency and thrombus formation with quantitative imaging and histological readouts.
- Analytics: Generates measurable outputs including thrombus size, endothelial coverage, and inflammatory cell infiltration for comparative analysis.
- Translational Research: Mirrors human AAA pathobiology, supporting biomarker alignment and preclinical validity.
- Enterprise Reuse: Establishes a reusable surgical model for iterative testing of biomaterials and device configurations across discovery campaigns.
Operational & Enterprise Impact
- Scientific Value: Reduces mechanistic ambiguity in aneurysm exclusion by enabling direct observation of thrombus evolution and graft integration.
- Operational Value: Enhances reproducibility through standardized elastase infusion and stent graft deployment techniques.
- Strategic Value: Improves go/no-go decisions by providing early biological feedback on device performance in a pathophysiologically relevant context.
- Portfolio Impact: Enables risk-based prioritization of endovascular candidates based on thrombus compatibility and endothelial healing profiles.
Implementation Considerations
- Requires expertise in microsurgical techniques, including aortic dissection, elastase infusion, and stent graft deployment.
- Depends on specialized instrumentation such as microsurgical clamps, infusion catheters, and angiography systems for patency confirmation.
- Necessitates cross-team standardization between surgical, imaging, and histology teams to ensure consistent aneurysm induction and exclusion outcomes.
- Involves adaptation considerations for different rat strains and aneurysm geometries due to variability in elastase diffusion and neck length.
- Limited by technical challenges in achieving consistent aneurysm morphology and preventing access-related complications such as aortic tear or thrombosis during stent graft introduction.
