Evaluation of pro-arrhythmic effects of the high-risk
drug dofetilide.
Results are shown for the MPS generated from the WTC cell line (A–C)
and the SCVI20 cell line (D–F). Panels (A, D) show the dose-dependent
change in action potential duration (corrected to 1 Hz beat rate).
Panels (B, E) show the beat shape metric triangulation calculated
as (APD80 – APD30)/APD80 for
voltage traces. Panels (C, F) show the percentage of the MPS exhibiting
arrhythmia-like event (red), weak signals (gray), or non-beating tissues
(black), as defined in Figure 1. Spontaneous voltage and calcium traces were considered for
this analysis. (G) Expected percent ion channel block determined from
tested drug doses from the literature. Statistical analysis: mixed-effects
analysis with the Geisser–Greenhouse correction followed by
Dunnett’s multiple comparison test to dose 0. Replicates are
from independent tissues. Reported significance levels are p < 0.05 (*), 0.01 (**), 0.001 (***), and 0.0001 (****).