Arterial Pouch Microsurgical Bifurcation Aneurysm Model in the Rabbit
May 14th, 2020
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.
As the development and testing of endovascular devices in intracranial aneurysm treatment is still greatly needed. We have designed a novel arterial pouch bifurcation model in rabbits. This model uses a single, highly standardized and easily reproducible microsurgical technique to create a autologous material pouch bifurcation aneurysms with modified and non-modified wall conditions in rabbits.
After confirming a lack of response to pedal reflex in an anesthetized adult rabbit, make a median skin incision from the manubrium sterni to the level of the larynx, and use a scalpel, surgical scissors, and forceps to sharply dissect the skin and soft tissue. Using micro forceps and surgical scissors, enter the anterior upper ridge of the sternocleidomastoid muscle immediately on the left side by blunt dissection. And macroscopically perform a blunt preparation to carefully distally separate the left common carotid artery from the vagal nerve to avoid laryngeal paresis.
Administer 40 milligrams per milliliter of papaverine locally into the artery and position the papaverine soaked artery below the autologous muscle tissue to protect the vessel from dehydration under the light of the surgical microscope. Switch sides and perform the same dissection on the right side of the animal as just demonstrated. When the right common carotid artery has been isolated inject 500 international units per kilogram of heparin systemically via a venous ear catheter.
After tightening the six zero ligature, use a temporary vessel clip to clamp the right common carotid artery as far distally as possible to avoid endothelial damage, to create a long vessel segment for irrigation to prevent thrombogenesis. To harvest the pouch, cut the distal vessel to the four zero nonabsorbable ligature. Then cut the vessel distal to the 6-0 non-absorbable ligature.
Meticulously clean the arterial pouch of all soft tissue and use a vessel clip to measure the length, width, and depth of the pouch. If a pouch degradation is needed, pre-incubate the cleaned pouch with 100 units of porcine elastase dissolved in five milliliters of Tris buffer at room temperature for 20 minutes. For further preparation of the common carotid artery, place two micro swabs directly beneath the common carotid artery to allow the vessel to be moved superficially and place an additional micro swab with a blue padding under the left artery at the distal third for better visualization of the artery.
Change sides to access the left side of the animal and use micro scissors and forceps to make a two millimeter fish mouth incision on the proximal side of the right common carotid artery. Use the second temporary vessel clip to clamp the left distal common carotid artery and clamp the proximal left common carotid artery with two additional temporary vessel clips. When all of the clamps have been placed, liberate the distal third of the left common carotid artery completely from the soft tissue and perform an arteriotomy.
Now flush the recipient vessel with heparinized saline and liberate the complex from a adventitia, then suture the right common carotid artery to the left common carotid artery. Transfer the arterial pouch from the heparinized saline solution into the surgical field where the bifurcation is planned. While keeping all of the aspects of the vessel complex hydrated with a continuous saline irrigation, suture the pouch to the vessel, and then remove all of the temporary vascular clamps in stepwise manner.
When all of the clamps have been removed, administer one milliliter of fluorescein intravenously to perform fluorescence angiography of the vessel complex. Then close the operative situs according to standard protocols. In this experimental analysis, animals with aneurysms induced by either the vital or elastase pouch methods demonstrated an increase in aneurysm size over time.
The average duration of the surgical procedure for the control group was 164 plus or minus 10 minutes compared to 201 plus or minus 13 minutes for the modified group. An average of 24 plus or minus one interrupted sutures was needed to create aneurysms in the controlled group, while 25 plus or minus two stitches were required in the elastase group. Measurements can then be performed by using three dimensional reconstructions of the MR imaging and detailed histological analysis.
A careful separation of the common carotid artery from the vagal nerve is essential for avoiding postoperative complications. To avoid thrombogenesis, keep the vessel and arterial pouch complex hydrated. Given the excellent patiency achieved with aneurysm growth over time, this model may serve as an important tool for the preclinical evaluation of novel endovascular devices.
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Overview
This study focuses on developing a novel arterial pouch bifurcation model in rabbits for the testing of endovascular devices aimed at treating intracranial aneurysms. The model provides a highly standardized and reproducible technique that simulates both modified and non-modified conditions of the arterial wall.
Key Study Components
Area of Science
- Neuroscience
- Vascular biology
- Endovascular device development
Background
- Existence of limitations in current aneurysm models.
- Importance of replicating hemodynamics of true bifurcations.
- Need for better experimental models for preclinical evaluation.
Purpose of Study
- To design an improved arterial pouch bifurcation model in rabbits.
- To facilitate testing of endovascular devices in a controlled environment.
- To validate the model's efficiency in replicating aneurysm growth over time.
Methods Used
- Microsurgical technique applied for creating autologous pouch bifurcations.
- Biological model involves isolating the common carotid arteries in rabbits.
- No multiomics workflows mentioned.
- Critical steps include clamping, heparinization, and suturing of the arteries.
- Postoperative monitoring for aneurysm growth and size measurement.
Main Results
- Induced aneurysms showed a significant increase in size over time.
- Results indicate the entailed surgical protocols were successful, with minimally invasive approaches evidenced by the handling of vessels.
- Time and material usage metrics were established during procedures, indicating reproducibility.
Conclusions
- The model enables better preclinical evaluation of new endovascular devices.
- It underscores the importance of maintaining vascular hydration to prevent thrombogenesis.
- Establishes a valid experimental approach for studying aneurysm development and device response.
Frequently Asked Questions
Executive Industry Relevance
Standardized animal models that replicate human aneurysm hemodynamics are critical for preclinical evaluation of endovascular devices. The arterial pouch bifurcation aneurysm model in rabbits enables controlled testing of device performance and biological response under reproducible conditions. This model supports translational continuity from discovery through preclinical device validation, reducing biological uncertainty in device development pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of aneurysm pathophysiology and device-tissue interactions in a controlled in vivo system.
- Supports biological de-risking by modeling both modified and non-modified aneurysm wall conditions.
- Facilitates predictive confidence in target selection for device-based interventions.
Screening & Assay Development
- Provides a validated, reproducible platform for screening endovascular devices in a physiologically relevant setting.
- Enables quantitative assessment of aneurysm growth and device efficacy using imaging and histological endpoints.
- Supports assay standardization and reproducibility for cross-study and cross-device comparisons.
Translational & Preclinical Research
- Aligns with disease-relevant hemodynamics and wall conditions for translational biomarker development.
- Ensures continuity from discovery-stage device concepts to preclinical validation and risk-adjusted advancement.
- Reduces translational gaps by modeling long-term patency and aneurysm progression under device treatment.
Pipeline & Workflow Integration
This rabbit bifurcation aneurysm model integrates into the preclinical evaluation phase of endovascular device development, bridging early discovery and translational research.
- Discovery Biology: Supports hypothesis testing on aneurysm formation and device interaction with vascular tissue.
- Screening: Delivers reproducible, quantitative outputs for device performance and aneurysm growth.
- Analytics: Enables measurement of aneurysm size and patency via imaging and histology for comparative analysis.
- Translational Research: Provides a disease-relevant system for preclinical validation of device safety and efficacy.
- Enterprise Reuse: Establishes a reusable, standardized animal model for ongoing device pipeline evaluation.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in device-tissue response.
- Operational Value: Enhances reproducibility, standardization, and scalability of preclinical device testing.
- Strategic Value: Improves go/no-go decisions and capital efficiency by providing robust preclinical data.
- Portfolio Impact: Enables risk-adjusted prioritization and advancement of device candidates.
Implementation Considerations
- Requires microsurgical expertise and familiarity with vascular dissection and anastomosis in rabbits.
- Demands access to imaging modalities such as fluorescence angiography and MR angiography for quantitative assessment.
- Necessitates cross-team standardization of surgical and analytical protocols for reproducibility.
- Adaptation to other animal models or vascular territories may require protocol modification.
- Careful handling is needed to avoid thrombogenesis and postoperative complications, as supported by the protocol.
