|Research Area||Bio Sciences|
|Principal Investigator(s)||Gernot Plank|
Computer simulations of the electrical activity of the heart using the bidomain equations have become commonplace during the last decade. However, even whenthe most powerful HPC resources are used, attempts to integrate behaviour from the protein scale of ion channels to the organ scale of cardiac arrhythmias remain enormously challenging and, typically, include significant simplifications to permit the exploration of the parameter space of interest in a tractable fashion. Typically, the geometry of the heart is represented in a stylized fashion or only parts of the heart are modeled. In constraining the degrees of freedom, the choice of the spatial discretization often leads to under-representation of the finer anatomical details and, quite often, ad-hoc adjustments of parameters are required to avoid artificial scaling effects. Many studies resort to using the simpler monodomain formulations which do not account for current flow in the extracellular space and, thus, feedback mechanisms of external current flow on the activation sequence is ignored; The specialised cardiac conduction system is typically not represented, preventing the simulation of the most important control case, the electric activity driven by the sinus node; And finally, myocardial membrane ion transport kinetics is modeled using simplified descriptions which are incapable of accounting for many potentially arrhythmogenic mechanisms.
This study aims to overcome these limitations by finely discretizing the heart to account for anatomical details while employing the latest descriptions of the membrane dynamics based on on Markov state models. After initially optimizing the codes, a micro-anatomically accurate mesh of a rabbit heart will be tuned and validated. Further, simulations will be executed to tackle questions related to arrhythmogenic effects of metabolic sinks. Effects of anatomical structure, functional heterogeneity and pharmacologically induced variations of the myocardial response on the electrocardiogram will also be investigated.