developing a rodent venoplasty balloon model for researching deep vein stenosis treatments

用于深静脉治疗研究的啮齿动物静脉成形术球囊模型

Deep vein obstructions from unresolved thrombi are a common consequence of deep vein thrombosis (DVT) and are one of the causes of post-thrombotic syndrome (PTS), costing billions of dollars in healthcare and significantly impacting the quality of life1,2,3. PTS is a unique inflammatory pathology with consequent vein wall fibrosis4 not fully captured in small animal DVT models5,6,7, and more importantly, previous models cannot evaluate the response to therapeutic interventions. Thrombotic venous obstructions are often treated by stenting and balloon venoplasty8,9; such interventions are hampered by a high reintervention rate due to restenosis and occlusion10,11,12.
Despite the availability of drug-coated balloons to address arterial-specific stenosis/occlusions, none exist for deep veins. The molecular mechanism behind restenosis is poorly understood in veins and has no direct therapy4. Therefore, our goal is to present an animal model that can test locally delivered therapeutics via venoplasty balloons simulating deep vein post-thrombotic obstructions. This model reproduces the post-thrombotic condition and evaluates how different types of venoplasty balloons affect the vein wall in vivo.

作者聚焦：在啮齿动物中利用静脉成形术球囊模型模拟深静脉的手术干预

啮齿动物下腔静脉成形术球囊模型

In our laboratory, led by Dr.Andrea 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 are 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 cell's genetics code, a process now 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.

开发用于研究深静脉狭窄治疗的啮齿动物静脉成形术球囊模型

developing-rodent-venoplasty-balloon-model-for-researching-deep-vein

Research

JoVE Journal

Medicine

Developing a Rodent Venoplasty Balloon Model for Researching Deep Vein Stenosis Treatments

Rodent Inferior Vena Cava Venoplasty Balloon Model

Balloon venoplasty is a commonly used clinical technique to treat deep vein stenosis and occlusion as a consequence of trauma, congenital anatomic abnormalities, acute deep vein thrombosis (DVT), or stenting. Chronic deep venous obstruction is histopathologically characterized by thrombosis, fibrosis, or both. Currently, no direct treatment is available to target these pathological processes. Therefore, a reliable in vivo animal model to test novel interventions is necessary. The rodent survival inferior vena cava (IVC) venoplasty balloon model (VBM) allows the study of balloon venoplasty in non-thrombotic and post-thrombotic conditions across multiple time points. The local and systemic effect of coated and uncoated venoplasty balloons can be quantified via tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent assay (ELISA), zymography, vein wall and thrombus cellular analysis, whole blood and plasma assays, and histological analysis. The VBM is reproducible, replicates surgical human interventions, can identify local vein wall-thrombi protein changes, and allows multiple analyses from the same sample, decreasing the number of animals required per group.

The protocol presents a survival rodent model to test venoplasty balloon (VB) interventions in non-thrombotic, thrombotic, and post-thrombotic deep veins.

Balloon venoplasty is a commonly used clinical technique to treat deep vein stenosis and occlusion as a consequence of trauma, congenital anatomic ...

科研

医学

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 disks 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 7-0 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 8-0 nylon U-stitch suture caudal 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 backloaded retrograde to blood flow into the infrarenal IVC caudal to the curved micro clip.Advance the balloon into the mid IVC using the Seldinger technique. Remove the sharpened guidewire 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 3-0 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.