Ischaemia, in which inadequate blood supply compromises and eventually kills regions of cardiac tissue, can cause many types of arrhythmia, some life-threatening. A significant component of this is the effects of the resulting hypoxia, and concomitant hyperklaemia and acidosis, on the electrophysiological properties of myocytes. Clinical and experimental data have also shown that regions of structural heterogeneity (fibrosis, necrosis, fibro-fatty infiltration) can act as triggers for arrhythmias under acute ischaemic conditions. Mechanistic models have successfully captured these effects in silico. However, the relative significance of these separate facets of the condition, and how sensitive arrhythmic risk is to the extents of each, is far less explored. In this work, we use partitioned Gaussian process emulation and new metrics for source-sink mismatch that rely on simulations of bifurcating cardiac fibres to interrogate a model of heterogeneous ischaemic tissue. Re-entries were most sensitive to the level of hypoxia and the fraction of non-excitable tissue. In addition, our results reveal both protective and pro-arrhythmic effects of hyperklaemia, and present the levels of hyperklaemia, hypoxia and percentage of non-excitable tissue that pose the highest arrhythmic risks. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
Keywords: cardiac electrophysiology; fibrosis; ischaemia; mathematical modelling; statistics.