Thrombosis, Vena Cava, Thromboplastin-Induced
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OVERVIEW
DOCUMENTS/REFERENCES
BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
Thrombotic cardiovascular diseases are the most common cause of death and disability in the developed world. Venous thrombosis is induced by ligature of the inferior vena cava in rats whose blood is made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. The thromboplastin-induced venous thrombosis model is widely used to study molecular mechanisms as well as the efficacy of antithrombotic agents.
ORGANISM
Rat
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of male or female Sprague-Dawley (SD) rats weighing 320 ± 30 g are used. Rats are anesthetized and the abdomen is surgically opened to expose the vena cava that is dissected free from surrounding tissue. Two loose sutures, about 1 cm apart, are prepared below the left renal vein. Test article and/or vehicle are administered intravenously (IV) 5 minutes, intraperitoneally (IP) 30 minutes or orally (PO) 1 hour before the IV injection of thromboplastin. Thirty seconds after thromboplastin injection, stasis is established by tightening the sutures. After 15 minutes of stasis the formed thrombus is removed from the segment, scored on a scale of 1 – 4 (according to the Wessler technique), blotted on filter paper and weighed both immediately (wet weight) and after drying at 37°C for 24 hours (dry weight). One-way ANOVA is used between each group and p<0.05 indicates significant anti-thrombosis relative to the vehicle treated group. Wessler technique thrombus scores are determined as follows: 0=fluid blood, 1=one or several small clots, 2=non occlusive thrombus filling 50% of the vascular segment, 3=non occlusive thrombus filling 75% of the vascular segment, 4=occlusive segment. Suggested Testing: n=6/group (study design dependent). Doses may be administered PO, IV, IP and SC. Assessments available: Biomarkers and histology services may be performed upon request.
CRITERIA FOR SIGNIFICANCE
p<0.05 compared to vehicle control is considered significant activity
TURNAROUND TIME
STANDARD
30 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Cardiovascular
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-2 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.
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