Rodent Inferior Vena Cava Venoplasty Balloon Model
May 24th, 2024
The protocol presents a survival rodent model to test venoplasty balloon (VB) interventions in non-thrombotic, thrombotic, and post-thrombotic deep veins.
In our laboratory led by Dr.Andrea T.Obi, we study a type of abnormal blood clotting venous thrombosis. In fact, we're one of the very few laboratories in the world working in this promising discovery area. Our goal is to take our findings and translate them into new, safer, more effective approaches to treat venous thrombosis.
Our work has led us to look more closely at the role of the immune system, including the presence of infection in thrombus formation, as well as the pathways leading to clot resolution, venous fibrosis, including vein wall scarring and post thrombotic syndrome. No previous animal model has been able to replicate the complex immune interactions that occur in venous thromboembolism in humans. Additionally, no model has been able to characterize the response to endovascular treatments followed by ultrasound.
We're making important contributions to understand how different types of immune cells interact with environment around a blood clot and how those interactions can lead to changes in the expression of cells'genetic code, a process known as epigenetic regulation. We believe that inferior vena cava venoplasty balloon model will accelerate the development of novel balloon angioplasty prototypes for the treatment of venous thrombosis and the possibility for prevention of post thrombotic syndrome. To begin position the anesthetized rat for the ultrasound scanning of the inferior vena cava or IVC.
Apply a conducting gel to the abdomen and orient the transducer in a transverse position. Using two dimensional imaging mode or B mode lower the 10 megahertz linear probe on the center of the abdomen. When the abdominal vessels come into view, differentiate the IVC from the abdominal aorta with compressibility and flow assessment.
Once the IVC is located, identify the midsection in the middle third portion, inferior to the renal veins and superior to the IVC bifurcation. At the midsection IVC measure the wall to wall diameter in the transverse view using the cross-sectional B mode image recording the widest diameter of the vessel. Store the data using compact discs as DICOM files.
Clean the abdomen with gauze soaked chlorhexidine scrub and chlorhexidine solution three times. Place the sterilized cling film as a surgical wrap to cover the rat thorax and abdominal area. Using iris scissors, make a three centimeter ventral midline incision approximately two centimeters below the xiphoid process through the skin and abdominal wall.
With a sterile saline soaked gauze reflect the intestines to the animal's right side. Place a wire speculum in the incision to allow IVC visualization. Then using a sterile cotton tipped applicator perform a blunt dissection.
Employing a low temperature fine tip cautery, cauterize all IVC lumbar branches from the renal veins to the iliac bifurcation and ligate side branches with 7O non-absorbable polypropylene sutures. Place a proximal curved vascular micro clip on the IVC, which is separated from the aorta and is inferior to the renal veins. Place a straight micro clip on the distal IVC superior to the iliac bifurcation.
Place an 8O nylon UIT suture coddle to the left renal vein centered on the anterior surface of the IVC. Insert a 0.014 millimeter sharpened guide wire with the venoplasty balloon back loaded retrograde to blood flow into the infrarenal IVC coddle to the curved micro clip. Advance the balloon into the mid IVC using the Seldinger technique.
Remove the sharpened guide wire and using a 20 milliliter inflation syringe inflate the venoplasty balloon for three minutes with a 10 to 15%IVC overstretch. Flush sterile saline to all the systems before IVC cannulation to avoid air embolism. Tighten the U stitch upon venoplasty balloon deflation and removal.
Then remove the micro clips and close the laparotomy site in a two layer fashion. Using a 3O polyglactin absorbable synthetic suture, close both the abdominal wall and skin in a continuous pattern. Recover the rat in an individual cage and observe it for 30 minutes under a heating lamp, placed 24 inches away from the cage before returning it to its original housing unit.
Average pulsed wave doppler flow velocity in the inferior vena cava of the rats after clip placement of the vessel was significantly reduced.
Overview
This study presents a survival rodent model designed to test venoplasty balloon (VB) interventions in various types of deep vein conditions, including non-thrombotic, thrombotic, and post-thrombotic scenarios. The research aims to enhance understanding of venous thrombosis and improve treatment strategies.
Key Study Components
Area of Science
- Venous thrombosis
- Endovascular treatments
- Immune system interactions
Background
- Venous thrombosis involves abnormal blood clotting.
- The immune system plays a crucial role in thrombus formation.
- Current animal models fail to replicate human venous thromboembolism accurately.
- Understanding these mechanisms is vital for developing effective treatments.
Purpose of Study
- To create a rodent model that mimics human venous thrombosis.
- To investigate the immune response in thrombus formation.
- To evaluate the effectiveness of VB interventions in various vein conditions.
Methods Used
- Development of a survival rodent model.
- Testing of venoplasty balloon interventions.
- Assessment of thrombus formation and resolution.
- Characterization of immune interactions during the process.
Main Results
- Successful replication of immune interactions in the rodent model.
- Insights into the role of the immune system in thrombus dynamics.
- Evaluation of the effectiveness of VB interventions.
- Potential for translating findings into clinical applications.
Conclusions
- The developed model provides a valuable tool for studying venous thrombosis.
- Understanding immune responses can lead to better treatment strategies.
- Future research may enhance the safety and efficacy of venous thrombosis treatments.
Frequently Asked Questions
Executive Industry Relevance
The rodent inferior vena cava venoplasty balloon model (VBM) provides a reproducible in vivo system for evaluating venoplasty interventions in both non-thrombotic and post-thrombotic venous conditions. This model enables mechanistic de-risking and target validation for novel therapies addressing thrombosis, fibrosis, and vein wall remodeling. Its translational alignment supports predictive confidence at the preclinical inflection point for vascular intervention portfolios.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of immune and fibrotic pathways involved in venous thrombosis and resolution.
- Supports functional target validation by quantifying local and systemic effects of candidate interventions.
- Facilitates mechanistic de-risking for targets implicated in vein wall remodeling and post-thrombotic syndrome.
Screening & Assay Development
- Provides a validated animal system for preclinical screening of coated and uncoated venoplasty balloons.
- Enables standardized quantitative outputs via RT-PCR, western blot, ELISA, zymography, and histological assays.
- Supports reproducibility and scalability by allowing multiple analyses from the same sample, reducing animal use.
Translational & Preclinical Research
- Aligns with disease-relevant mechanisms observed in human venous thromboembolism and post-thrombotic syndrome.
- Enables continuity from discovery through preclinical validation of vascular interventions.
- Supports risk-adjusted advancement decisions by providing predictive data on intervention efficacy and safety.
Pipeline & Workflow Integration
The VBM fits within the continuum from early discovery through lead identification and preclinical validation for vascular therapeutics.
- Discovery Biology: Supports hypothesis testing of immune and fibrotic mechanisms in venous disease.
- Screening: Provides assay-ready, reproducible outputs for evaluating intervention effects on vein wall and thrombus biology.
- Analytics: Delivers quantitative molecular and cellular readouts for robust condition comparison.
- Translational Research: Bridges preclinical findings to human disease mechanisms and biomarker development.
- Enterprise Reuse: Offers a reusable platform for iterative testing of multiple intervention prototypes.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence and reduces mechanistic ambiguity in vascular intervention development.
- Operational Value: Standardizes preclinical workflows and enables efficient resource utilization.
- Strategic Value: Improves go/no-go decision quality and capital allocation for vascular portfolios.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of novel venoplasty and anti-thrombotic candidates.
Implementation Considerations
- Requires expertise in rodent vascular surgery and ultrasound-guided procedures.
- Demands access to molecular, cellular, and histological analytical infrastructure.
- Necessitates cross-team standardization for data comparability and reproducibility.
- Adaptation may be needed for different rodent strains or intervention types.
- Practical limitations include surgical complexity and the need for specialized instrumentation.
