Atrioventricular nodal electrophysiology: still exciting after all these years.

The anatomical atrioventricular node was first described by Tawara in 1906.1 Although some surmised the node to be the region responsible for delay between contraction of atria and ventricles, Erlanger in 1912 localized the major portion of delay to a latency at the transition between atrial and nodal fibers.2 Nearly a century of research on properties of the atrioventricular (AV) node has substantiated the suggestion of Hoffman and Cranefield3 in 1960 that the term “atrioventricular node” should be used to describe “the entire complex of fibers functionally interposed between atrial fibers proper and His bundle fibers proper” (page 132) and not just the compact node of Tawara, since nodal-like properties have been found outside the compact node.4–8 Thus, the posterior nodal extension, the focus of the study by Dobrzynski et al9 in this issue of Circulation Research, is now included as part of the electrophysiological AV node. Identified as a nodal structure by its histological features, a bundle of tightly packed small cells extending posteriorly along the tricuspid annulus,10 it has nodal-like electrophysiological properties (low-amplitude slowly rising action potentials and slow activation) and it is likely the slow pathway in AV nodal reentry.6 – 8,11 Dobrzynski et al,9 by characterizing properties of this region further through the use of immunofluorescent techniques (see below), have provided additional evidence that it is indeed part of the electrophysiological AV node. Among the properties that were assigned to the AV node is the ability to initiate heart beats. In fact, Engelmann described “AV nodal rhythm” (page 48) in 1903 even before the node was discovered.12 After Hering in 1910 destroyed the sinus node in hearts of dogs and rabbits, he found that the interval between atrial and ventricular contractions was reduced, sometimes disappeared, and sometimes became negative.13 He suggested that when impulses originated in the upper part of the node, an AV interval approaching normal might occur, in the mid portion of the node the interval would approach zero, and in the lower portion of the node, a ventricular-atrial sequence would result. Subsequently, Zahn in 191314 warmed different parts of the AV node in experimental animals with a “thermode” inserted through the atrial wall and described rhythms originating in the upper, middle, and lower AV node. Thereafter, the concept of upper, middle, and lower nodal rhythms became entrenched in electrocardiographic literature using the criteria established from the early experimental studies. However, electrocardiographers later recognized that the relative retrograde and orthograde speed of conduction from a nodal pacemaker was not uniform and would influence the relationship between P and QRS waves.12 Therefore, a nomenclature was adopted by some that did not intend to indicate the exact site of AV node impulse initiation. The location of the AV junctional pacemaker still remained a mystery. Little progress in locating the pacemaker site causing AV nodal rhythms occurred until 1958 when transmembrane action potentials were first recorded from AV node of rabbit and dog.4 Spontaneous diastolic depolarization was recorded in the mid and lower node in the rabbit heart under conditions in which AV nodal rhythm occurred in vitro, and Hoffman, Cranefield, and associates described that pacemaker activity of the node was confined mainly to the lower node (called the NH region) and the His bundle,3 a conclusion supported by others.15 However, some studies in the dog AV node in vitro described automaticity in all regions of the AV node.16 AV nodal automaticity and pacemaker currents have also been described in small pieces of nodal tissue in vitro,17 but the location from which they came was not documented. One of the difficulties in locating the site of pacemaker activity in the AV junction has been technical. Mapping the spread of activity is essential. This method involves registration of intraor extracellular electrical activity at numerous sites. Obtaining detailed maps from within the electrophysiological node has been extraordinarily difficult since the extracellular signal from nodal-type cells is very small and simultaneous transmembrane potential recordings from multiple sites are nearly impossible to obtain.18–20 Therefore, application of optical mapping with fluorescent dyes to the study of AV nodal electrophysiology has been a major advance since it enables signals to be registered from many sites simultaneously. Dr Efimov, the senior author of the study by Dobrzynski et al,9 was among the first to apply this methodology to the AV node.21 Optical mapping has provided important new information on slow and fast pathway conduction and AV nodal reentry.22 It is, therefore, logical that the next step was to map the origin of rhythms that occurred when the dominant sinus pacemaker was eliminated (Dobrzynski et al9 in this issue). The activation maps for such “escape rhythms” show that the majority originate in the posterior extension of the AV node. Previous studies had shown that this region has the propensity for automatic impulse initiation in the presence of -adrenergic stimulation, but the region was not identified as nodal.23 The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Department of Pharmacology and Center for Molecular Therapeutics, Columbia University, College of Physicians and Surgeons, New York, NY. Correspondence to Andrew L. Wit, PhD, Department of Pharmacology, College of Physicians and Surgeons of Columbia University, 630 W 168th St, New York, NY 10032. E-mail [email protected] (Circ Res. 2003;93:1018-1019.) © 2003 American Heart Association, Inc.