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. 2017 Nov 21;7:15922. doi: 10.1038/s41598-017-16218-3

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Restitution Properties. Using an S1S1 pacing protocol, restitution curves show that APD80 decreased as pacing cycle length decreased. This relationship was fitted using a two phase exponential curve. (a) The restitution curve shifted minimally with the addition of JNJ-303 in isolation. (b) Restitution downshifted with isoprenaline, upshifted with I_Ks block, and further upshifted with I_Kr block. (c) Functional refractory period was reached when S1S1 pacing lost capture. The refractory period significantly decreased with isoprenaline, and increased with both I_Ks and I_Kr blockers. (d–f) Restitution curves were plotted for endo, mid, and epi areas of the transmural surface indicating similar changes across all three areas.