Microsurgical Creation of Giant Bifurcation Aneurysms in Rabbits for the Evaluation of Endovascular Devices
September 8th, 2023
Here, we describe the technique for the microsurgical creation of giant bifurcation aneurysms in rabbits for the evaluation of endovascular devices.
Reliable animal models for giant aneurysms are rare. However, these models are extremely important for the development of new endovascular devices to treat these aneurysms safely. The advantages of this technique are true bifurcation design for giant aneurysms, minimal morbidity, and high aneurysm patency rates with high comparability to humans.
Giant aneurysms are challenging lesions to treat in humans. This protocol focuses on the creation of these aneurysms and offers the possibility for testing of new endovascular devices. Demonstrating the procedure will be Camillo Sherif.
He's the senior research leader of our study group and has extensive experience with rabbit aneurysm models. After anesthetizing the rabbit, intubate the animal using a tube having four millimeter diameter and 18 millimeter length. Monitor the depth of anesthesia with a toe pinch every 15 minutes and adjust if necessary.
Using clippers, shave the area from the angle of the jaw down to the animal's thorax and disinfect the shaved surgical area. For microsurgical creation of bifurcation aneurysms, incise the skin along the midline from the angle of the jaw down to the manubrium sterni of the animal using a scalpel. Perform blunt dissection in the subcutis.
Next, under a surgical microscope, dissect a two to three centimeters long branchless segment of the left external jugular vein. Dropwise, apply 4%propiverine repeatedly on the vessels to prevent vasospasm, and five milligrams per milliliter of neomycin sulfate for infection control. Perform proximal and distal ligation on the vein using 6-0 non-resorbable sutures.
Measure the vein length, harvest the vein segment, and place it in a heparinized saline solution. Prepare both common carotid arteries or CCAs by dissecting them from the carotid bifurcation to their origin. Watch carefully for the medial arterial branches which supply the laryngeal, tracheal, and neural structures.
Apply a temporal microsurgical clip at the distal end of the right CCA. Using polyfilament 6-0 non-resorbable sutures, ligate the right CCA proximally directly above the brachiocephalic trunk and cut it. With the help of anatomic microforceps and microscissors, remove the adventitia at the anastomosis site of both vessels.
Then clip the anastomosis site of the left CCA distally and proximally. Make an arteriotomy at the left CCA according to the size of the planned anastomosis with the right CCA and the venous pouch. Determine the length of the arteriotomy by the diameter of the contralateral carotid artery which is about two millimeters and the planned aneurysm neck size.
The size should be between 3 and 15 millimeters considering the possible aneurysm and neck sizes of this model. Clean the aneurysm site with five milliliters of heparinized saline. Use four to five non-resorbable 10-0 monofilament sutures to suture the posterior circumference of the right CCA stump with the previously described arteriotomy of the left CCA.
Cut the stump of the right CCA longitudinally to a length of 1 to 1.5 centimeters. Anastomose the posterior part of the venous pouch with the arteriotomy of the left CCA using 10-0 sutures. Then suture the rear side of the venous pouch with the posterior wall of the right CCA with three to four sutures.
Suture the anterior anastomosis in the same sequence as demonstrated before. Release the temporal clip on the right CCA. Usually anastomosis leaks.
Use this to wash air and blood clots out. Then seal the anastomosis with fat derived from the subcutaneous tissue of the surgical approach and fibrin glue. After the surgery, intravenously administer acetylsalicylic acid maintaining a dosage of 10 milligrams per kilogram of body weight.
Apply transdermal fentanyl patch on the shaved region for three days to achieve postoperative analgesia. Subcutaneously administer low molecular heparin daily for two weeks to achieve postoperative anticoagulation. With the demonstrated regime, it was possible to achieve 0%mortality and patency in 11 out of 12 aneurysms.
The aneurysm lengths varied between 21.5 to 25.6 millimeters with neck widths ranging from 7.3 to 9.8 millimeters. An image of stent-assisted embolized giant aneurysm that was captured after the aneurysm retrieval is shown here. For giant aneurysms, it is important to begin the anastomosis on the rear side.
This gives better sight and control for the most challenging sutures of the procedure. Endovascular devices can be implanted and used for research on occlusion rates and device behavior. Afterwards, histopathological examination can show endothelization of devices and lesion pathology.
Examining the aneurysm wall using MR imaging followed by histopathological correlation could enhance the understanding of MR wall imaging in humans.
Overview
This study outlines a microsurgical technique to create giant bifurcation aneurysms in rabbits, aimed at advancing the evaluation of endovascular devices. The developed model offers a reliable platform for assessing treatments for giant aneurysms, which are challenging to manage in humans.
Key Study Components
Area of Science
- Neurosurgery
- Vascular biology
- Endovascular therapy
Background
- Giant aneurysms are critical conditions in human patients.
- Current animal models for studying these aneurysms are limited.
- Development of new devices for aneurysm treatment requires reliable models.
- This technique aims to minimize morbidity and enhance aneurysm patency rates.
Purpose of Study
- Create a microsurgical training model for giant bifurcation aneurysms.
- Facilitate clinical research on endovascular devices.
- Ensure high comparability of the model to human conditions.
Methods Used
- Microsurgical techniques were performed on a rabbit model.
- Giant bifurcation aneurysms were created via specific vascular interventions.
- Post-operative care included administration of anticoagulants.
- The procedure maintained 0% mortality and high patency in generated aneurysms.
Main Results
- The technique achieved successful creation of aneurysms with measured lengths and neck widths.
- Device implantation was possible, allowing for further research and evaluation of occlusion rates.
- Histopathological analysis can lead to better understanding of the lesion pathology.
- Demonstrated effectiveness in creating a reliable model for studying aneurysm behaviors.
Conclusions
- The study provides a validated approach for using rabbit models in aneurysm research.
- This model enhances the assessment of endovascular devices and their mechanisms.
- Outcomes could inform future therapeutic strategies for giant aneurysms in humans.
Frequently Asked Questions
Executive Industry Relevance
Reliable in vivo models for giant bifurcation aneurysms are essential for preclinical evaluation of endovascular devices targeting high-risk vascular lesions. This microsurgical rabbit model enables translational assessment of device performance, occlusion rates, and biological compatibility under clinically relevant hemodynamic conditions. The approach supports predictive confidence and de-risking at the device discovery and validation inflection point.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables mechanistic interrogation of device-tissue interactions in a controlled, disease-relevant system.
- Supports functional validation of endovascular device concepts prior to clinical translation.
- Facilitates biological de-risking by modeling human-like hemodynamics and coagulation.
Screening & Assay Development
- Provides a standardized, reproducible platform for quantitative assessment of device occlusion and patency rates.
- Enables comparative evaluation of multiple device prototypes under uniform conditions.
- Supports assay development for imaging, histopathology, and device integration endpoints.
Translational & Preclinical Research
- Aligns with translational biomarker strategies by enabling MR imaging and histopathological correlation.
- Ensures continuity from device discovery through preclinical validation in a model with high human comparability.
- Supports risk-adjusted advancement decisions for device candidates based on robust in vivo data.
Pipeline & Workflow Integration
This model bridges early device discovery, lead identification, and preclinical validation for endovascular technologies targeting giant aneurysms.
- Discovery Biology: Supports hypothesis testing of device mechanisms and biological responses in a relevant vascular context.
- Screening: Delivers reproducible, quantitative readouts for device performance and aneurysm patency.
- Analytics: Enables measurement of occlusion rates, imaging endpoints, and histopathological outcomes for cross-device comparison.
- Translational Research: Facilitates alignment with clinical imaging and pathology standards for translational continuity.
- Enterprise Reuse: Establishes a reusable, validated animal model for ongoing device evaluation and optimization.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in device efficacy and safety prior to clinical studies.
- Operational Value: Standardizes preclinical workflows and enhances reproducibility across device programs.
- Strategic Value: Improves go/no-go decision-making and capital allocation for device portfolios.
- Portfolio Impact: Enables risk-adjusted prioritization and advancement of high-potential endovascular technologies.
Implementation Considerations
- Requires microsurgical expertise and access to specialized animal surgical facilities.
- Demands imaging and histopathological infrastructure for endpoint analysis.
- Necessitates cross-team standardization of surgical and analytical protocols.
- Adaptation to other species or vascular territories may require protocol modification.
- Model limitations include species-specific differences and scalability constraints.
