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Chloroquine effect on rotor termination under paroxysmal and chronic atrial fibrillation. 2D simulation study

Abstract:

Atrial fibrillation (AF) is the most common prevalent cardiac arrhythmia. If the paroxysmal AF (pAF) is not treated it could become chronic AF (cAF). Blockade of inward rectifying potassium (IK1) and acetylcholine-activated potassium (IKACh) currents by the antimalarial drug chloroquine could play a role as antiarrhythmic drug in human AF. We simulated the effects of chloroquine on human atrial tissue to study its effect on rotor termination, under pAF and cAF conditions. For this, we modified a human cell model to obtain pAF and cAF models and we developed a model of chloroquine effects on IK1 and IKACh. Rotors were generated in a 2D model of atrial tissue and different chloroquine concentrations were applied. Our results show that chloroquine blocks both currents, which results in action potential duration (APD) lengthening. Chloroquine has a greater effect on pAF conditions and high chloroquine concentration is needed to achieve similar effects in cAF. In pAF, was necessary 0.3 μM or more, in order to terminate the rotor, however, in cAF, was necessary a higher chloroquine concentration (0.5 μM). Our results suggest that the antimalarial drug chloroquine could be a potent antiarrhythmic agent in the treatment of pAF at concentrations from 0.3 μM and in the treatment of cAF at higher concentrations, from 0.5 μM.