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Shifting Paradigms: Examining
Pro-Thrombotic Activity from a
Safety Perspective
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 test article prior to FeCl3
-monitor for development of thrombus
-use real-time monitor of blood flow, time to occlusion
Validation
- reduced concentrations of FeCl3, vessel vulnerability present
Effects of various concentrations FeCl3 on carotid artery blood flow
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61
mL/min
Time (minutes)
Concetration-dependent effects of Ferric Chloride on
Carotid Arterial Thrombosis in CD-1 Mice
Carotid Artery Flow
Vehicle (PBS, 3.5% FeCl3- Lot SZBE1900V) (n=5)
Vehicle (PBS, 3.0% FeCl3- Lot SZBE1900V) (n=10)
Vehicle (PBS, 2.8% FeCl3- Lot SZBE1900V) (n=10)
Vehicle (PBS, 2.5% FeCl3- Lot SZBE1900V) (n=10)
FeCl3
Reducing FeCl3 reduces thrombosis – prothrombotic window opens
0
5
10
15
20
25
30
35
40
45
50
55
60
0
10
20
30
40
50
60
70
80
90
100
3.5% FeCl3
Lot SZBE1900V
3.0% FeCl3
Lot SZBE1900V
2.8% FeCl3
Lot SZBE1900V
2.5% FeCl3
Lot SZBE1900V
ProThrombotic
OcclusionTime(min)
Incidenceofnon–Occlusion(%)
Concetration-dependent effects of Ferric Chloride on
Carotid Arterial Thrombosis in CD-1 Mice
Occlusion time
Incidence of non-occlusion
4/10
1
out
of 1
1
out
of 1
2/10 6/10
0/7
?

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Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective

  • 1. Shifting Paradigms: Examining Pro-Thrombotic Activity from a Safety Perspective
  • 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 test article prior to FeCl3 -monitor for development of thrombus -use real-time monitor of blood flow, time to occlusion Validation - reduced concentrations of FeCl3, vessel vulnerability present
  • 3. Effects of various concentrations FeCl3 on carotid artery blood flow 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 -1 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 61 mL/min Time (minutes) Concetration-dependent effects of Ferric Chloride on Carotid Arterial Thrombosis in CD-1 Mice Carotid Artery Flow Vehicle (PBS, 3.5% FeCl3- Lot SZBE1900V) (n=5) Vehicle (PBS, 3.0% FeCl3- Lot SZBE1900V) (n=10) Vehicle (PBS, 2.8% FeCl3- Lot SZBE1900V) (n=10) Vehicle (PBS, 2.5% FeCl3- Lot SZBE1900V) (n=10) FeCl3
  • 4. Reducing FeCl3 reduces thrombosis – prothrombotic window opens 0 5 10 15 20 25 30 35 40 45 50 55 60 0 10 20 30 40 50 60 70 80 90 100 3.5% FeCl3 Lot SZBE1900V 3.0% FeCl3 Lot SZBE1900V 2.8% FeCl3 Lot SZBE1900V 2.5% FeCl3 Lot SZBE1900V ProThrombotic OcclusionTime(min) Incidenceofnon–Occlusion(%) Concetration-dependent effects of Ferric Chloride on Carotid Arterial Thrombosis in CD-1 Mice Occlusion time Incidence of non-occlusion 4/10 1 out of 1 1 out of 1 2/10 6/10 0/7 ?