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Engineered heart tissues in high‐throughput toxic compound screening
Author(s) -
Rufanova Victoriya,
Baehr Walter,
Gerger Michael,
Badic Anesa,
Wakatsuki Tetsuro
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.570.1
Objective To validate the utility of engineered heart tissues (EHTs) in high‐throughput toxic compound screening. Methods and results Neonatal rat heart cells were mixed with collagen/Matrigel and formed spontaneously beating miniaturized (4x4 mm 2 ) EHTs. Cardiac twitch and resting force were measured by Palpator™. Effects of known cardiotoxic doxorubicin, daunorubicin and isoproterenol as well as nontoxic dobutamine and cyclosporin A were determined after 3 day treatments with the contractility of EHTs and their viability. Doxorubicin and daunorubicin (both 200 nM) significantly (75%) decreased cardiac contraction with a mild reduction in cell viability. Isoproternol (5μM) treatment induced arrhythmia and decreased cardiac twitch by 55% with a loss in cellular viability (15%). Dobutamine (5 μM) and cyclosporin A (1 μM) induce no and 50% decrease in cardiac contractility, respectively. Both drugs had no effect on EHTs viability. Conclusion Detection of arrhythmic inducing and cardiotoxic drugs using the Palpator system was successful. Cardiotoxic drugs in future screenings of unknown compounds would enable toxic detection of chemical library.