2.8 In silico model reconstruction
The O’Hara-Rudy (ORd) human ventricular model(O’Hara, Virág, Varró & Rudy, 2011) was modified to incorporate the actions on multi-channel block of HCQ, including the dose-dependent block of INa,, ICaL,, Ito, IKr, IKs IK1 and the Na+-Ca2+ exchange current, INCX. This model was selected as it was developed from and validated against experimental data from human ventricular cells and found suitable for studying actions of drugs. The simulations evoked action potentials by a supra-threshold stimulus in control runs and following application of HCQ, and combined application of HCQ and AZM. Action potential time courses characterized by AP durations at 90% repolarisation (APD90) and maximal upstroke velocity (MUP) and the underlying ion channel currents targeted by the drugs were recorded for analysis.