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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
Effect of E-4031 on proarrhythmic potential
- QRS duration (no change) and paced QT interval (increase)
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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)
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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)
Effect of E-4031 on proarrhythmic potential
- QTpeak interval (increase) and Tpeak – Tend duration (increase)
-rate dependent
0
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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)
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90
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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)
Effect of E-4031 on proarrhythmic potential
- MAPD90 (increase) and MAP triangulation (increase)
- rate dependent
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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)
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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)
Effect of E-4031 on proarrhythmic potential
- incidence of early afterdepolarizations (increase)
- rate dependent
0
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10
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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)
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