Populations of models: A new approach for understanding the mechanisms of atrial fibrillation

Inter-subject variability explains the diverging effects to pharmacological treatments of AF reported in the literature. A population of 173 mathematical models of remodeled human atrial tissue with realistic inter–subject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The ranges of 6 biomarkers measured from the patch clamp studies were appropriately covered. The resulting population shows that multiple combinations of variations in the ionic conductances result in AF models that cover the range of biomarkers measured experimentally. Introducing restrictions associated with pacing rate limits the number of models, restricts calcium transient amplitudes, and shows significant differences in the distribution of variation of parameters associated with INa, IKr and INaK ionic currents. Populations of models will improve the development of new antiarrhythmic treatments preventing undesired effects associated with differences between individuals