Why Does Extracellular Potassium Rise in Acute Ischemia? Insights from Computational Simulations

Hyperkalemia, acidosis and hypoxia are the three main components of acute myocardial ischemia. In particular, the increase of extracellular K+ concentration (hyperkalemia), has been proved to be very proarrhythmic because it sets the stage for ventricular fibrillation. However, the intimate mechanisms remain partially unknown. The aim of this work was to investigate, using computational simulation, the relationship between the different phases of hiperkalemia, the activity of the ion channels and the changes related to the action potential in the absence of coronary flow. Our results show that the partial inhibition of the sodium-potassium pump is the main cause of extracellular potassium accumulation. However, the cause of the plateau phase could be due to the appearance of action potential alternans, which reduces the net potassium efflux and limits the increase of extracellular potassium concentration.