Primary negativity does not predict dominant pacemaker location: implications for sinoatrial conduction

Abstract

Activation sequence maps derived during normal sinus rhythm from extracellular potentials in the canine right atrium exhibit widely separated sites of origin. The objectives of this study were to characterize the distribution of pacemakers within the right atrium and to determine the relationship of pacemaker action potentials to sites of earliest surface activation as well as to local extracellular electrograms. The right atria of six adult mongrel dogs were rapidly excised under deep pentobarbital sodium anesthesia and perfused with 95% O2-5% CO2 Krebs-Henseleit solution. Action potentials from the epicardial surface were recorded throughout the region bounded by the crista terminalis laterally and the atrial septum medially. Simultaneously, unipolar extracellular electrograms were recorded from 250 endocardial sites. The earliest pacemakers preceded the earliest electrogram by 63 +/- 34 ms; the latest pacemakers followed the earliest electrogram by 71 +/- 40 ms. Primary negativity in the extracellular electro gram did not predict the site of the earliest or dominant pace maker and in some cases was associated with the latest pace makers. We conclude that primary negativity and/or the sites of earliest activation reflect the point at which the impulse engages atrial myocardium, not the site of earliest pacemaker activity. As such, early extracellular activation appears to represent sites of exit from a relatively insulated sinus node.

Differential Expression of Gap Junction Proteins in the Canine Sinus Node

“…14 The complex connexin phenotypes in sinus node pacemaker cells may also explain, in part, the electrophysiological data of Bromberg et al, 47 who used floating microelectrodes to record action potentials from cells within the canine sinus node while simultaneously recording from multiple extracellular sites. They showed that although the earliest intracellular activation occurred within the central portion of the sinus node, the earliest extracellular activation occurred at the superior and inferior poles of the nodal region, suggesting discrete propagation exit sites from the node.…”

“…Perhaps certain types of intercellular channels facilitate conduction between the pacemaker and atrial myocardium and correlate with the dispersed exit sites observed in our previous studies. 47 Other types of channels may subserve the electrotonic interactions that determine the final rate and site of the dominant pacemaker region within the sinus node and at the same time inhibit rapid impulse propagation or depolarization wave fronts within the pacemaker matrix. Answers to these questions will require more extensive electrophysiological and anatomic-biochemical studies in both dispersed cell aggregates and in vivo preparations.…”

Interbeat interval variability in isolated working rat hearts at various dynamic conditions and temperatures

“…Literature data are available from isolated pacemaker cells [17,33], cell clusters [14,17], and isolated right atrium preparations [4,5,7,22,35]. BI variability of pacemaker cells and cell clusters was mostly quantified by the coefficient of variation C BI = 100 SD BI BI --1 (given as a percentage) or related measures [6,14,17,33].…”

Optical Mapping of the Sinoatrial Node and Atrioventricular Node

“…The earliest site of atrial endocardial or epicardial activation is not necessarily the actual location of the pacemaker [10]. These findings suggested that the SAN either: (i) consisted of multiple pacemakers that could entrain one another; or (ii) contained multiple exit sites from which atrial surface activation would first occur [8,9].…”