On the frequency of automaticity during ischemia in simulations based on stochastic perturbations of the Luo–Rudy 1 model

Aims: To compute the effects of parameter perturbations for single ischemic cardiac cells, and to determine how perturbations influenced the tendency for the cells to undergo spontaneous depolarization (automaticity) during 20 min of acute ischemia.Methods: A modified Luo–Rudy 1 cell model was used. Since the range of biological variation and measurement errors is largely unknown, we conducted our study of the consequences of perturbations under the assumption that cell model parameters have a normal distribution with a 10% standard deviation. A total of 10 000 random cell realizations were tested while varying important Luo–Rudy cell model parameters. Ischemia was modelled by deterministic functions chosen for the expected values of crucial ion concentrations and gating parameters as they developed with time, while realizing the respective parameter values from static normal distributions with a 10% standard deviation.Results and conclusion: It was found that the tendency towards automaticity did increase as the stochastic parameters were varied. In particular, cells with standard Luo–Rudy parameter values did not become automatic during ischemia, whereas a significant portion of the cells with randomized parameter values did. The relative importance of model parameter variations was also determined and a sodium m-gate activation parameter was identified as the most critical parameter. The frequency of arrhythmic events during acute ischemia is known to be bell-shaped, with a peak at around 7–8 min after the onset of ischemia. Our simulations display a similar peak in the frequency of automaticity.