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This customized assessment leverages physiologically relevant paradigms with expert design and follow through to enable key lead optimization in drug discovery. Subjects are dosed with either vehicle or active test article prior to administration of FeCl3 to the external surface of the carotid artery. Following this exposure to FeCl3, 3 thrombotic occlusion of the carotid artery occurs in a matter of minutes in the untreated animal. Test article efficacy can be quantitated as alterations in coronary artery blood flow along with time to occlusion.
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CorDynamics conducts thrombosis experiments – using small and large animals
Mouse ferric chloride model of arterial thrombosis
1) instrumentation to monitor carotid artery flow
- monitor artery flow prior to and after FeCl3
- FeCl3 migrates to lumen, results in endothelial injury
2) administer putative anti-thrombotic prior to FeCl3
-monitor for development of thrombus
-use real-time monitor of blood flow, time to occlusion
Pharmacological validation
- heparin (anticoagulant)
MOUSE THROMBOSIS MODEL
Effects of heparin on carotid artery blood flow
MOUSE THROMBOSIS MODEL
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-5 5 15 25 35 45 55 65
Car
oti
d B
loo
d F
low
(m
L/m
in)
Time (minutes)
Effects of Heparin on Ferric Chloride (3.5 %)-Induced Carotid Arterial Thrombosis in the Mouse
[vertical line is FeCl3 exposure]
Vehicle (0.9% NaCl, n=5)
Heparin (200U/kg, n=5)
Effects of heparin on time to occlusion
MOUSE THROMBOSIS MODEL
0
10
20
30
40
50
60
70
Vehicle (0.9% NaCl, n=5) Heparin (200U/kg) (n=5)
Tim
e (m
inut
es)
Effects of Heparin on the Ferric Chloride (3.5%)-Induced Carotid Arterial Thrombosis in the Mouse
Occlusion Time
No occlusion
For more information, on this model and our other drug discovery and drug safety
capabilities, please visit us at www.cordynamics.com
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