Safety pharmacology studies using EFP and impedance
Alison Obergrussberger1, Krisztina Juhasz1, Ulrich Thomas1
1Nanion Technologies GmbH, Gabrielenstr. 9, 80636 Munich, Germany.
Journal of Pharmacological and Toxicological Methods
|April 17, 2016
Summary
This study demonstrates that combining extracellular field potential (EFP) and impedance measurements with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) effectively detects drug effects on cardiac function and electrophysiology for improved safety pharmacology.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Stem Cell Technology
Background:
- Extracellular field potential (EFP) recordings are established for cardiac and neuronal monitoring.
- Impedance technology is underutilized for functional assessment.
- Combining EFP, impedance, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offers insights into drug effects on human cardiomyocyte contraction and electrophysiology.
Purpose of the Study:
- To demonstrate the utility of a beating hiPSC-CM monolayer on the CardioExcyte 96 system for detecting drug-induced changes in contraction and electrophysiology.
- To evaluate the combined EFP and impedance recording modes for drug screening.
Main Methods:
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured on NSP-96 plates for the CardioExcyte 96 system.
- Recordings were performed in combined EFP and impedance modes at physiological temperature.
- The effects of known cardiac drugs (E4031, dofetilide, pentamidine, isoproterenol, nifedipine) were assessed.
Main Results:
- EFP and impedance measurements successfully detected drug-induced alterations in hiPSC-CMs.
- hERG blockers (E4031, dofetilide) decreased beat rate, and EAD-like events indicative of Torsades de Pointes (TdP) were observed.
- Isoproterenol and nifedipine increased beat rate.
- Pentamidine exhibited concentration- and time-dependent effects over 30 hours.
Conclusions:
- Combined EFP and impedance measurements from hiPSC-CMs are critical for assessing proarrhythmic risk of drug candidates, aligning with the Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative.
- This 96-well plate format provides electrophysiology and contractility data from the same human cardiomyocyte monolayer, enhancing cardiac safety testing.
- The integrated approach offers a standardized and efficient method for preclinical cardiac safety evaluation.
Keywords:
CardioExcyte 96DofetilideE4031EAD-likeExtracellular field potentialImpedanceIsoproterenolNifedipinePentamidineSafety pharmacologyMore Related Videos
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