Abstract 14399: Characterisation of the Cellular Electrophysiology of Subsidiary Right Atrial Pacemaker Tissue, and its Utility for Biopacemaking via the Chimaeric Pacemaker Channel HCN212
Background: Sick sinus syndrome (SSS) is common, often requiring electronic pacemaker implantation. Gene therapy (biopacemaking) may be an alternative. For sinus node (SAN) disease repair may be better than an ectopic de novo biopacemaker due to the complex nature of the SAN. We hypothesised that identification and characterisation of a subsidiary pacemaker in the SAN region would facilitate development of a SSS model, and that expression of a chimaeric pacemaker channel (HCN212) in this region would accelerate pacing.
Methods: The upper 2/3 of a rat right atrium was removed in vitro, the leading pacemaker sites of these preparations (SSS) were identified by activation mapping then characterised. Further SSS preparations were injected with Ad5HCN212 in this region. During tissue culture electrical activity was monitored using bipolar electrodes.
Results: Uninjected SSS paced slower than the control (n=7 P<0.001). The subsidiary pacemaker was HCN4 -ve and Connexin-43 +ve, in contrast to the SAN. It was located close to the superior aspect of the inferior vena cava (fig 1). The cell size of the subsidiary pacemaker was smaller than working myocardium (n=6 P<0.001) and comparable to that of the SAN. Pacing was beta adrenergic responsive and was partially dependent on If current. HCN212 expression significantly increased the spontaneous pacing rate of the subsidiary tissue (n=8 P<0.001).
Conclusions: There is subsidiary pacemaker tissue close to the superior aspect of the IVC that shares some characteristics of the SAN. These results suggest that adenovirus mediated expression of HCN channels in a bradycardic sinus node can increase the pacing rate. Figure 1. Representative activation maps of rat SAN preparations, the leading pacemaker site is shown (white asterisk) with immunohistochemistry for HCN4 (green) and Cx43 (red) (A and C). B) full map; D) SSS map. CT, crista terminalis; I/SVC, inferior/superior vena cava; RAA, right atrial appendage; scale bars in A and C = 100 μm.
- © 2010 by American Heart Association, Inc.