In silico modelling of DHA effects. (A) Simulated APs at 2 Hz based on Shannon model for WT, LQT2 (gKr = 0%), and LQT2+DHA (gKs +100%) cardiomyocytes. (B) Results of single-cell in silico simulations for combinations of parameters gKs and gCa, L at 1.0–2.5 Hz. Every square represents one simulation. Shaded squares represent parameters where pacing was successful (shade encodes APD90). Pink and purple squares represent simulations where 2:1 block and EAD occur, respectively. Black squares represent simulations where the cell was unable to repolarize. Numbers in bottom right corners of each plot indicate simulations resulting in block, EAD or permanent depolarization. (C) Normalized repolarization reserve calculated from the number of single-cell pacing simulations in the parameter space 0 < gKs/gKs,orig < 1 (step 0.1) and 1 < gCaL/gCaL,orig < 5 (step 0.2) that did not result in EAD, block or permanent depolarization. Reference for normalization is the number of simulations for WT at 1 Hz that did not show these pro-arrhythmic features. AP, action potential; DHA, docosahexaenoic acid; EAD, early after depolarization; LQT2, long QT Type 2; WT, wild type.
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