Atrial fibrillation is a common cardiac arrhythmia. The disturbance of the normal repolarization process due to heterogeneous myocyte-fibroblast coupling might play a role for this disease. We investigate this interaction in the heterogeneous atrium using a computational approach.Human atrial myocyte computational models representing 10 different regions of the atrium were each coupled to a human atrial fibroblast model and the impact of the myocyte-fibroblast coupling on action potential measures was investigated.Myocytes from the pulmonary vein are affected most by the coupling to fibroblasts. Action potential amplitude is reduced from 105 mV to 94 mV and the upstroke velocity changes from 192 V/s to 152 V/s, potentially reducing the conduction velocity. In general, the action potential duration of myocytes with short action potentials is prolonged and that of those with long is shortened.The large effect on pulmonary vein action potentials is mainly due to reduced I K1 in these cells compared to other regions of the atrium. The strong effects of fibroblast coupling to pulmonary vein myocytes are likely to be an additional reason for the crucial role of the pulmonary veins in atrial fibrillation.
IntroductionCardiac arrhythmias are a high burden to the health systems and quality of life. The most common arrhythmia is atrial fibrillation (AF), which affects more than 10% of the population older than 70 and more than 1% of the population in general with an upward trend [1]. The mechanisms of initiation and perpetuation of this arrhythmia are not yet fully understood. Both trigger and substrate changes need to be present in order to allow progression of AF. In this regard, the pulmonary vein (PV) regions play an important role as they are often source of triggered activity. Substrate changes, e.g., by fibroblasts coupling to myocytes, disturb the normal repolarization process. This might play a significant role in the perpetuation of AF.Cardiac myocytes from different regions of the atrium show differences in ion channel density [2]. This manifests in action potential (AP) morphology changes and in action potential duration (APD) variations. This heterogeneity of the AP seems to play an important role for the normal repolarization process leading to an overall more homogeneous repolarization as early activated cells tend to have a longer APD than late activated cells [2]. During progression of AF, the remodeling processes involve the activation of fibroblasts and an increase in fibrosis in addition to electrophysiological remodeling. Up to now, it is not clear if the fibroblasts couple to atrial cardiomyocytes and how they influence the regionally varying APs. Additionally, it is not known if and how myocyte-fibroblast coupling contributes to the perpetuation and progression of atrial fibrillation. This work uses a single cell computational approach to investigates the effects of coupled fibroblasts on atrial cells from different regions of the atrium before electrophysiological remodeling happens.
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