Sensitivity of the Human Ventricular BPS2020 Action Potential Model to the In Silico Mechanisms of Ischemia

Myocardial acute ischemia is due to a reduced or suppressed blood supply to the heart. It heavily impacts the electrical and mechanical functionality of cardiomyocytes (CMs), up to cell necrosis. We evaluate the effects of the three main consequences of acute ischemia (hypoxia, acidosis, and hyperkalemia) on the recent Bartolucci-Passini-Severi (BPS2020) model of human adult ventricular CM. We run a sensitivity analysis considering different ischemia severity, mechanisms, and formulations of the ATP-sensitive K+ current (IKATP), initially not included in BPS2020. We further compare our results with other in silico and in vitro data and evaluate the BPS2020 capability to simulate alternans in ischemia. Hyperkalemia remarkably depolarized the resting membrane potential and reduced the maximum upstroke velocity. Acidosis slightly shortened the action potential (AP) duration. Hypoxia mainly reduced the AP duration and its peak. Our results agree with simulations performed with other in silico models. Finally, the full ischemia model produced alternans at fast pacing. Our sensitivity analysis demonstrates that the BPS2020 model correctly recapitulates the acute ischemia effects, and it is suitable for more advanced simulations.