Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis

Summary

The mouse complete stasis model of inferior vena cava thrombosis yields quantifiable amounts of vein wall tissue and thrombus. It has proven useful for evaluating interactions between the vein wall and the occlusive thrombus and in assessing the progression from acute to chronic inflammation.

Abstract

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). In the United States (U.S.), the high morbidity and mortality rates make VTE a serious health concern ^1-2. After heart disease and stroke, VTE is the third most common vascular disease ³. In the U.S. alone, there is an estimated 900,000 people affected each year, with 300,000 deaths occurring annually ³. A reliable in vivo animal model to study the mechanisms of this disease is necessary.

The advantages of using the mouse complete stasis model of inferior vena cava thrombosis are several. The mouse model allows for the administration of very small volumes of limited availability test agents, reducing costs dramatically. Most promising is the potential for mice with gene knockouts that allow specific inflammatory and coagulation factor functions to be delineated. Current molecular assays allow for the quantitation of vein wall, thrombus, whole blood, and plasma for assays. However, a major concern involving this model is the operative size constraints and the friability of the vessels. Also, due to the small IVC sample weight (mean 0.005 grams) it is necessary to increase animal numbers for accurate statistical analysis for tissue, thrombus, and blood assays such as real-time polymerase chain reaction (RT-PCR), western blot, enzyme-linked immunosorbent (ELISA), zymography, vein wall and thrombus cellular analysis, and whole blood and plasma assays ^4-8.

The major disadvantage with the stasis model is that the lack of blood flow inhibits the maximal effect of administered systemic therapeutic agents on the thrombus and vein wall.

Protocol

1. Mouse Anesthesia Procedures

1. Animals are removed from their cage and placed in an anesthetic pre-operative induction chamber for gas induction at 5% isoflurane and 100% oxygen, at a flow rate of 0.5 liters per minute (vaporizer controlled).
2. Mice are sedated in the anesthetic induction chamber, removed from chamber and the ventral abdomen is shaved with electric clippers, or maintained within the chamber if a hair depilatory is used (1min).
3. While still under sedation, they are weighed, the eyes are lubricated with sterile opthalmic ointment and then placed in a dorsal recumbancy on a warm water circulating heating device under general ....

Discussion

The Mouse Complete Stasis Model of Inferior Vena Cava Thrombosis can be performed on multiple strains of mice of varying ages. The model is most suited to mice of at least 20 grams in weight. This animal model of venous thrombosis allows investigators to study inflammatory interactions between the vein wall and the occlusive venous thrombus. From our experience, we have found that 10 or more animals per group are needed to obtain statistical significance between the groups for thrombus weights, vein wall inflammatory cel.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Isoflurane gas
Prolene 7-0 suture
Vicryl 5-0 suture
Skin glue
Eye lube
Nolvasan Solution or bacteriostatic solution
Stereomicroscope scope
MediCapture
Cotton Applicators
2x2 Gauze
Heating pad
Anesthetic machine
Glass bead instrument sterilizer
Micro surgical instruments
Abdominal Restrainers