LAUSR

Hyperkalemia, acidosis, and anoxia are major pathophysiological conditions of myocardial ischemia. Cardiac arrhythmias induced by these conditions are widely investigated. However, the myocardium contractile function during acute ischemic perturbations is not fully explored. A fully coupled electromechanical computational model is used to investigate cardiac inotropic response under various ischemic conditions. The coupling is accomplished with a detailed myofilament model (MF) that allows for a dynamic feedback between both electrophysiology and contractile model components. Additionally, an ATP-sensitive potassium channel (KATP) kinetics is incorporated in the model to account particularly for anoxia effects. Simulations are performed on a highly resolved cellular scale where Ca2+ sensitivity to ischemic perturbations is well predicted and fed to the MF model, thus inotropic alterations due to ischemia can be calculated. Both Ca2+ transient and twitch dynamics are calculated to establish an ischemic-mechanics relationship. When compared with non-ischemic control case, Ca2+ levels have shown to be attenuated as a result of both anoxia and acidosis but not with hyperkalemia perturbations. Mechanical responses represented by twitch dynamics as triggered by these changes in Ca2+ behavior are computed. Simulations suggest that, the activation kinetics of the KATP – channel (% f-ATP) is the main ischemic parameter that significantly alters the cellular excitation-contraction coupling process in the form of; action potential shortening, reduced excitability, delayed recovery, Ca2+ attenuation, significant decrease in the myocardium twitch production.