Ionic mechanisms underlying atrial electrical remodeling after a fontan-style operation in a canine model

Abstract

AbstractAtrial arrhythmia is an important cause of late death in patients after the Fontan-Style operation. However, the detailed electrophysiological characteristics of the post-Fontan atrium and its underlying mechanisms are largely unknown. In this study, we investigated electrophysiological characteristics and the ionic remodeling in the right atrium (RA) of a canine model after the Fontan operation. We performed the operation of RA to pulmonary artery connection to mimic the Fontan operation. We undertook hemodynamic measurements, cardiac electrophysiological studies, and ion current measurements. The expression of ionic channels was analyzed by PCR and western-blotting. Our Fontan model induced RA hypertension, enlarged the size of RA, and increased atrial fibrosis, representing the classic characteristic of Fontan patients. In the Fontan group, the atrial effective refractory period and the active potential duration were reduced, and the atrial tachycardia has been more often to be induced. The electrical conduction mapping showed that the Fontan group reduced the conduction velocity. The Fontan operation significantly down-regulated the expression of KCND3/Kv4.3, CACNA1C/Cav1.2 and SCN5A, but up-regulated the expression of KCNJ2/Kir2.1. Correspondingly, The Fontan operation reduced transient-outward (Ito) and L-type Ca2 (ICa,L) and INa currents, while increasing the inward-rectifier current (IK1). Thus, the net shortening of the action potential in the post-Fontan atrium is associated with the altered expression of ionic channels which disturbed the balance between inward and outward currents. Taken together, the Fontan operation induces the ionic remodeling, and thus altered electrophysiological characteristics of the right atrium, improving our understanding on the pathophysiology of atrial arrhythmias in Fontan patients.