Cardiac Memory in Human Atria and Relation to Arrhythmogenesis

Abnormal adaptation of action potential duration (APD) to changes in heart rate (HR) has been suggested as an indicator of increased arrhythmic risk. In this study, we investigate the mechanisms underlying APD rate adaptation in human atrial cells and its relationship to arrhythmogenesis. Simulations are performed using action potential computational models and results are compared with experimental data from the literature. APD rate adaptation in response to sudden sustained FIR changes is shown to take more than 8 minutes to be completed in the simulations and two main adaptation phases can be identified: a fast initial one due to the Na+/Ca2+ exchanger and the L-type calcium current; and a subsequent slow accommodation determined by intracellular Na dynamics. Both APD adaptation dynamics and its underlying mechanisms are found to be consistent in different species. Alterations in ionic mechanisms leading to delayed APD adaptation are associated with increased proarrhythmic risk.