Fig. 4.
Simulations of alternans and ORM-10962. A) The longest basic cycle length at which was alternans detected in control condition and several combinations of NCX and ICaL availability representing simulated ORM-10962 (NA = not available = no alternans). See Appendix C for a full frequency-alternans relationship at all the studied conditions. B) Calcium transient at 1000 ms bcl pacing. C) Calcium concentration in the network SR at 1000 ms bcl pacing. D) Calcium concentration in the junctional SR at 280 ms bcl pacing. E) A breakdown of the effect of five treatments simulating ORM-10962 (50% NCX availability and the five listed availabilities of ICaL) compared to the baseline model using a population of models approach. For each of 684 tested models in the population and for each treatment, a simulation was classified as ‘alternans attenuated’ if the treatment shifted alternans onset to shorter basic cycle length, ‘alternans promoted’ if alternans onset was shifted to longer basic cycle lengths, and ‘alternans maintained’ if alternans first appeared at the same basic cycle length. See Appendix D for a breakdown of how much was alternans promoted or attenuated in each condition.