Formulation of ATP sensitive K+ Current and Action Potential Shape in Models of Human Ventricular Myocytes

The contribution of the ATP-sensitive K+ (KATP+) current to the action potential is an important component of cardiac ischaemia. The purpose of this study was to investigate how the formulation of IK(ATP) influences action potential shape and duration in the Ten Tusscher-Panfilov 2006 model of human ventricular myocytes. We compared four different IK(ATP) formulations, which were inserted in the epicardial variant of the cell model embedded in a 2D monodomain tissue model. The results demonstrate that inserting IK(ATP) in the cell models shortens APD as intracellular ATP concentration is reduced, consistent with experimental findings. Although the current-voltage properties of each IK(ATP) formulation were different, each formulation had a similar effect on the properties of the tissue model

Simulating the Effect of Global Cardiac Ischaemia on the Dynamics of Ventricular Arrhythmias in the Human Heart

Cardiac arrhythmias are significant causes of death in the world, and ventricular fibrillation is a very dangerous type of cardiac arrhythmia. Global myocardial ischemia is a consequence of ventricular fibrillation (VF) and has been shown to change the dynamic behaviour of activation waves on the heart. The aim of this thesis is to use computational models to study the behaviour of re-entry in the human ventricles when the heart becomes globally ischaemic. The effects of two ischaemic components (hyperkalaemia and hypoxia) on spiral wave re-entry behaviour in two dimensional (2D) ventricular tissue using two ventricular action potential (AP) models were simulated (Ten Tusscher et al. 2006 (TP06) and O’Hara et al. 2011 (ORd)). A three dimensional (3D) model of the human ventricles is used to examine the influence of each ischaemic component on the stability of ventricular fibrillation. Firstly, the main ventricular AP models relevant to this thesis are reviewed. Then, the current-voltage properties of four different IK(ATP) formulations are examined to assess which formulation was more appropriate to simulate hypoxia/ischaemia. Secondly, how the formulation of IK(ATP) influences cell excitability and AP duration (APD) in models of human ventricular myocytes is studied. Finally, mechanisms underlying ventricular arrhythmia generation under the conditions of ischaemia are investigated