Shift of dominant pacemaker site during reflex vagal stimulation is the result of propagation failure

Abstract

Background: Reflex vagal activity causes abrupt heart rate slowing with concomitant caudal shifts of the dominant pacemaker site within the sinoatrial node (SAN). However, neither the mechanisms responsible nor their dynamics have been investigated fully. Objective: To elucidate the mechanisms driving pacemaker shift during reflex vagal stimulation. Methods: Optical maps of right atrial activation were acquired in a rat working heart-brainstem preparation (n=10) during baroreflex and chemoreflex stimulation before and after If channel inhibition with ivabradine. Results: Baroreflex induced caudal pacemaker shifts occurred with increases in cycle length (ΔCL=73±102 ms, 95% CI [42, 105]) and significant slowing of conduction through the rostral SAN. Chemoreflex stimulation also triggered shifts coincident with large CL increases (ΔCL=117±69 ms, 95% CI [74, 161]). In contrast, carbachol produced shifts that occurred with small, non-significant CL changes. Post-ivabradine, CL increased significantly faster during reflex and carbachol responses. Conclusion: Studies suggest acetylcholine (ACh) slows pacemaker rate disproportionately in the rostral SAN, enabling less ACh-sensitive caudal cells to assume control. Our findings with carbachol are consistent with such rate entrainment, but results with reflex stimulation are not. Reflex induced shifts coincided with failure of propagation from the rostral SAN. The onset of this effect was If dependent. We conclude that the dominant pacemaking region is defined by both rate and capacity to drive atrial activation.