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. 2020 May 18;176(1):103–123. doi: 10.1093/toxsci/kfaa058

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© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 5. — Slowed beat rate increases the predictivity of positive inotropes (PIs) in 3D engineered heart tissues (EHTs). Contraction analysis was carried out using EHTs with 6 of the PIs from the drug test set: epinephrine (Epi), forskolin (For), levosimendan (Lev), pimobendan (Pim), dobutamine (Dob), and milrinone (Mil) which had been predicted with variable accuracy (Figure 4A, web tool). In all cases, the drugs (applied as a high concentration bolus) increased contraction amplitude (CA) but only at 0.5 and 0.7 Hz, and sometimes at 1 Hz, with the largest effects seen in contraction time (CT) also often occurring at these frequencies. Scatter plots show percentage changes relative to baseline at respective frequency. Averaged peaks for force are shown for baseline (BL, black peaks) versus after treatment in EHTs paced at 0.5 Hz (blue peaks) or 2.0 Hz (red peaks). Dunnett’s stats versus baseline at respective frequency: *p < .05; **p < .01; ***p < .001; ****p < .0001.