From microscopic calcium sparks to the ECG: Model reduction approaches for multi-scale cardiac simulation

摘要

Malfunctions in the intracellular calcium handling system are being increasingly linked to multiple cardiac arrhythmias. Feedback mechanisms in spatio-temporal sub-cellular calcium dynamics are critical for the development of spontaneous calcium waves which may underlie ectopic focal activity. However, computational models which account for such processes are unsuitable for incorporation into organ-scale simulations, thus limiting the ability of multi-scale modeling approaches to explain and dissect the role of spatio-temporal calcium handling in organ-level arrhythmogenesis.