Leveraging the Langendorff Model to Detect Proarrhythmia
-
Upload
cordynamics -
Category
Health & Medicine
-
view
191 -
download
2
Transcript of Leveraging the Langendorff Model to Detect Proarrhythmia
![Page 1: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/1.jpg)
![Page 2: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/2.jpg)
CorDynamics can use multiple approaches to examine effects of test
articles on proarrhythmia
Isolated Heart option
- multiple indices as arbiters of increased vulnerability to
arrhythmia during exposure to test articles
- instantaneous monophasic action potential variability
- Tpeak – Tend duration
- QTpeak interval
- monophasic action potential duration
- incidence of early afterdepolarizations
- rate dependence of all parameters
![Page 3: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/3.jpg)
Effect of E-4031 on proarrhythmic potential
- QRS duration (no change) and paced QT interval (increase)
0
10
20
30
40
50
60
70
80
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartQRS Interval
CL 750 ms (80 bpm)
CL 500 ms (120 bmp)
CL 250 ms (240 bpm)
0
50
100
150
200
250
300
350
400
450
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartQT Interval
CL 750 ms (80 bpm)CL 500 ms (120 bmp)CL 250 ms (240 bpm)
![Page 4: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/4.jpg)
Effect of E-4031 on proarrhythmic potential
- QTpeak interval (increase) and Tpeak – Tend duration (increase)
-rate dependent
0
25
50
75
100
125
150
175
200
225
250
275
300
325
350
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartQTpeak Interval
CL 750 ms (80 bpm)
CL 500 ms (120 bmp)
CL 250 ms (240 bpm)
0
10
20
30
40
50
60
70
80
90
100
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartTpeakTend Interval
CL 750 ms (80 bpm)
CL 500 ms (120 bmp)
CL 250 ms (240 bpm)
![Page 5: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/5.jpg)
Effect of E-4031 on proarrhythmic potential
- MAPD90 (increase) and MAP triangulation (increase)
- rate dependent
0
25
50
75
100
125
150
175
200
225
250
275
300
325
350
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartMAPD90
CL 750 ms (80 bpm)CL 500 ms (120 bmp)CL 250 ms (240 bpm)
0
25
50
75
100
125
150
0 0.1 1 10
ms
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartTriangulation
CL 750 ms (80 bpm)
CL 500 ms (120 bmp)
CL 250 ms (240 bpm)
![Page 6: Leveraging the Langendorff Model to Detect Proarrhythmia](https://reader031.fdocuments.in/reader031/viewer/2022020218/559f60271a28ab68528b46ba/html5/thumbnails/6.jpg)
Effect of E-4031 on proarrhythmic potential
- incidence of early afterdepolarizations (increase)
- rate dependent
0
5
10
15
20
25
30
35
40
45
50
55
60
0 0.1 1 10
counts
Concentration (µM)
Effect of E-4031 in Isolated Rabbit HeartEAD/min
CL 750 ms (80 bpm)
CL 500 ms (120 bmp)
CL 250 ms (240 bpm)