Simplistic, Model-Independent Protocol for Assessing Dynamic Action Potential Duration Adaptation

Paavo Ala-Mononen1, Huy Tran2, Venla Koivunen1, Jussi T Koivumäki1
1Tampere University, 2Tampere Universities (TAU)


Abstract

Adaptation of action potential (AP) duration (APD) to heart rate is a fundamental electrophysiological property of cardiomyocytes, yet no widely adopted protocol exists for its systematic evaluation.

We propose a simple dynamic APD restitution protocol that is model independent, links periodic pacing variability to physiological heart rate variability, and requires minimal user input. Its simplicity enables adoption across simulation frameworks and allows cross-context comparisons. We evaluate the protocol against two common approaches: the ‘mathematical' approach using approximately 1000 AP cycles to reach steady state and the ‘practical' using only tens of cycles to reach a quasi-steady-state. Furthermore, we show that the protocol's periodic pacing feature distinguishes short-term memory properties across human atrial and ventricular cell models and under atrial fibrillation-related phenotypic changes.