Computational simulation of ischemia-induced hyperkalemia using the BPS human ventricular action potential model

This study is aimed to test the ability of Bartolucci-Passini-Severi (BPS) model to reproduce the ischemia-induced hyperkalemia, a characteristic feature of the acutely ischemic heart disease. The BPS model is an action potential model of ventricular cardiomyocytes, which correctly reproduces the physiological APD-[Ca2+]e dependence. The simulations consisted of a 30-minutes progressive ischemic period on an isolated cardiomyocyte. In the simulations hyperkalemia was monitored alongside other variables, including ionic currents, potassium fluxes and concentrations. The simulations revealed that, from the onset of ischemia till the 4.4th minute post-occlusion, the extracellular potassium time course is in agreement with other models. However, after this time point the model shows some discrepancies compared to experimental values. The results demonstrated that at this point the sarcoplasmic calcium release suddenly interrupts which could be related to the failure of opening and closing gates of Ryanodine receptors (RyR). In the setting of BPS model the performance of these gates are governed by a third factor, adaptation gate. This gate provides the range of responsiveness for functioning of the opening and closing gates. In the BPS model according to the calcium concentration in the cytosol the adaptation gate failed to provide a window big enough to cover the range functioning of those gates. Thus, through a sensitivity analyses we chose the best set for adaptation gate in a manner to overcome the malfunctioning of opening and closing gates. After all the modifications the results by BPs model have improved significantly.