Objective: 

A typical feature in atrial fibrillation (AF) is a change in the intercellular communication via gap junctions, which are found at the lateral cell sides in AF, while they are normally located at the cell poles. We aimed to study, whether these lateral gap junctions might be functional and which are the consequences.

Methods: 

Left atrial tissue samples were obtained from patients with chronic AF (with metoprolol n=85; without n=38) or sinus rhythm (SR)(with metoprolol n=20; without n=17). The tissue samples were submitted to 64 electrode mapping and transverse and longitudinal conduction velocity were assessed. Collagen I, Cx40 and Cx43 were measured by Western Blot and their localisation was determined by immunohistology. In addition, we studied the functional consequences of lateralisation in a computer simulation.

Results: 

Mapping of human atrial tissue revealed higher longitudinal (V(L)) than transverse propagation velocity (V(T)). However, in AF V(T) was significantly higher (0.37±0.04 m/s, p=0.01) as compared to SR (0.21±0.02 m/s) this was enhanced in AF. If AF-patients received metoprolol V(T) was not increased (0.25±0.01, p=0.01). Moreover, in AF patients the propagation pattern was more irregular. Consistently, immunohistology showed enhanced expression of Cx43 and Cx40 at the lateral sides of the cells in AF. Cx43, but not Cx40-lateral-expression was significantly antagonized by metoprolol-treatment. Computer simulation revealed that lateral gap junctions can stabilize conduction against uncoupling, can balance out inhomogeneities, but enhance V(T). The susceptibility to conduction block at tissue expansion becomes significantly higher.

Conclusion: 

The mapping results indicate that the lateralisation of gap junctions seems to be functional. This is further supported as metoprolol treatment antagonized both Cx43 lateralization and AF-induced increase in transverse conduction velocity. Computer simulation indicates that this might be a compensatory effect e.g. against fibrotic uncoupling, but also enhances transverse conduction velocity and thereby can stabilize re-entrant pathways.