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The xCELLigence RTCA CardioECR system is a non-invasive, label-free platform that records cellular impedance and electrical field potential in paralle to simultaneously assess cardiomyocyte contractility, viability and electrophysiology.
Many novel oncology therapeutics may induce cardiotoxicity by inhibiting survival pathways which are shared by both tumors and cardiac cells. As complex mechanisms underlie drug-induced toxicity, some compound effects will only become evident after longer incubation times. Multiplexing impedance and MEA with cTnI release assay allows for a simultaneous assessment of short-term and long-term as well as structural and functional drug-induced cardiotoxicity from a single well.
Unlike lapatinib and nilotinib, ponatinib and doxorubicin caused a concentration- and time-dependent increase in cTnI release (right panels, represented as counts, dashed line indicates baseline cTnI levels), which correlated with reduced Cell Index (CI) values (left panels). The CI can also be affected by changes in the morphology or contractility of the cardiomyocyte monolayer as seen after addition of nitrendipine. Therefore, the CI could not be used as a direct measurement for structural cardiotoxicity.
Whereas addition of nilotinib and lapatinib caused a (functional) contractile/electrophysiological deficit, doxorubicin exhibited a long-term toxic effect in both MEA and impedance measurements. While lapatinib and nilotinib did not cause structural toxicity as measured by cTnI release, ponatinib and doxorubicin induced a dose- and time-dependent increase in cTnI release which correlated with reduced cell index values.