STRUCTURE/FUNCTION RELATIONSHIP OF THE AV NODE

Case Western Reserve University, Cleveland OH

Investigators

Linked publications & trials

Abstract

Despite significant recent advances in the treatment of supraventricular arrhythmias, the mechanisms governing conduction through the atrioventricular node (AV) remain poorly understood. These difficulties reflect the profound complexity of the 3D structure of functionally diverse cellular structures that comprise the relatively small AV node. Hypotheses: Functional properties of the AV node are determined by two levels of structural 3D organization of the node: vertical and horizontal. Vertically the node has three major layers: a superficial endocardial layer of Na-dependent transitional AN-cells, a middle Ca- dependent compact node (N-cells) in the shape of a flattened football, and a deep layer (bundle) of NH-type Na-dependent cells. Horizontally the node can be divided into the proximal and distal nodes (PN and DN). PN is anterogradely driven by the driving force from wide atrial approaches. Conduction through the PN is preferentially longitudinal and decremental in amplitude, because of weak side-to-side connections. DN is wrapped in unevenly thin collar of connective tissue protruding from the central fibrous body. DN may be driven transversely by the endocardial transitional cells or longitudinally by the proximal midlayer. Due to an electrotonic barrier imposed by the connective tissue, weak side-to- side connections, and post-repolarization refractoriness in DN, the transverse excitation has a lower safety factor. Nevertheless this pathway is preferential at long coupling intervals due to the short conduction path. Functional differences between these two sources of excitation constitute the dual pathway electrophysiology, namely the difference between the slow and fast pathways (SPW and FPW). Methods: Structure-function relationship of the AV node will be revealed by state-of-the-art high temporal and spatial resolution 3D fluorescent imaging with voltage-sensitive dyes combined with micro- and macro electrode recordings. Conduction through the AV node will be modulated spatially (reversible ablation of SPW or FPW by perinodal cooling to 15 C) and temporarily (anterograde and retrograde premature stimulation protocol). Electrophysiological and morphological studies will be summarized in a mathematical model of the AV node. Importance: Knowledge of the structure-function relationship of the AV node will assist the clinical evaluation of AV nodal functional properties. The new concept of the dual pathway electrophysiology will guide electrophysiological procedures of AV nodal modification.