Abstract 10165: Structure-function of the Sinus Node: Implications for Source-sink Sino-atrial Matching
Background: Development of a biological pacemaker as an alternative treatment strategy for sinus node (SN) disease or heart block has been focused primarily on cellular mechanisms of pacemaking. However, SN in large mammals is a complex 3D structure, which evolved to electrically match the SN source with atrial sink with varying heart rate requirements. We aimed to investigate the mechanisms of heartbeat generation in the canine SN.
Methods: Canine right atrial preparations (n=5) were coronary perfused and optically mapped using ANBDQBS, near infrared voltage sensitive dye, to assess the origin and spread of excitation in transmural layers. The SN structure was mapped using Masson-trichrome staining and immunofluoroscence. Accurate anatomical localization of the site of origin of the heartbeat in SN and its exit to the atria was performed during normal sinus rhythm, atrial pacing and targeted reversible cryoablation.
Results: We found that the heartbeat originated in SN and excited nearby atrial myocardium in four steps: 1) Origin of action potential at a wandering leading pacemaking cluster in the HCN4+/Cx43- SN; 2) Slow intra-SN conduction during phase 4 depolarization from the HCN4+/Cx43- SN cells to HCN4+/Cx43+ transitional tissue (42 to 65ms), 3) Fast conduction through sino-atrial exit pathways (SAEP) (4 to 6 ms); 4) Atrial focal breakthrough. Significant part of lateral SN (~60%) remained not fully depolarized at the time of atrial breakthrough, suggesting poor coupling within SN and presence of functional insulating barrier. Targeted cryoablation on the earliest atrial activation site (fast SAEP) allowed activation of other slower pathways, proving existence of preferential SAEP. We also detected subsidiary pacemaker activity is an islands of HCN4 + cells outside of SN (n=2). Extensive cryoablation of SN enabled subsidiary pacemakers to dominate.
Conclusion: We present evidence for the presence of multiple competing pacemaking clusters within the canine HCN4+/Cx43- SN, which are coupled via HCN4+/Cx43- transitional SN to SAEPs and atrium. Our findings showed that the intricate redundant source-sink coupling between SN and atrium is required to assure safe pacemaking function.
- © 2013 by American Heart Association, Inc.