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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Drug Discovery: New Models for Investigating Thrombosis in Drug Compounds
1.
2. 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)
3. Effects of heparin on carotid artery blood flow
Effects of Heparin on Ferric Chloride (3.5 %)-Induced
Carotid Arterial Thrombosis in the Mouse
[vertical line is FeCl3 exposure]
Carotid Blood Flow (mL/min)
3.5
3.0
2.5
2.0
1.5
Vehicle (0.9% NaCl, n=5)
1.0
Heparin (200U/kg, n=5)
0.5
0.0
-5
5
15
25
35
Time (minutes)
45
55
65
4. Effects of heparin on time to occlusion
Effects of Heparin on the Ferric Chloride (3.5%)-Induced
Carotid Arterial Thrombosis in the Mouse
Occlusion Time
70
No occlusion
60
Time (minutes)
50
40
30
20
10
0
Vehicle (0.9% NaCl, n=5)
Heparin (200U/kg) (n=5)
5. For more information, on this
model and our other drug
discovery and drug safety
capabilities, please visit us at
www.cordynamics.com