title: Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria.
abstract: Surface electrode recordings cannot delineate the activation within the human or canine sinoatrial node (SAN) because they are intramural structures. Thus, the site of origin of excitation and conduction pathway(s) within the SAN of these mammals remains unknown. Canine right atrial preparations (n=7) were optically mapped. The SAN 3D structure and protein expression were mapped using immunohistochemistry. SAN optical action potentials had diastolic depolarization and multiple upstroke components that corresponded to the separate excitations of the node and surface atrial layers. Pacing-induced SAN exit block eliminated atrial optical action potential components but retained SAN optical action potential components. Excitation originated in the SAN (cycle length, 557+/-72 ms) and slowly spread (1.2 to 14 cm/sec) within the SAN, failing to directly excite the crista terminalis and intraatrial septum. After a 49+/-22 ms conduction delay within the SAN, excitation reached the atrial myocardium via superior and/or inferior sinoatrial exit pathways 8.8+/-3.2 mm from the leading pacemaker site. The ellipsoidal 13.7+/-2.8/4.9+/-0.6 mm SAN structure was functionally insulated from the atrium. This insulation coincided with connexin43-negative regions at the borders of the node, connective tissue, and coronary arteries. During normal sinus rhythm, the canine SAN is functionally insulated from the surrounding atrial myocardium except for 2 (or more) narrow superior and inferior sinoatrial exit pathways separated by 12.8+/-4.1 mm. Conduction failure in these sinoatrial exit pathways leads to SAN exit block and is a modulator of heart rate.
authors.affiliation: Department of Biomedical Engineering, Washington University, St Louis, Mo. 63130, USA. vadimfed@gmail.com
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Fedorov
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: Matthew
authors.initials: M
authors.lastname: Hemphill
authors.forename: Christina M
authors.initials: CM
authors.lastname: Ambrosi
authors.forename: Roger
authors.initials: R
authors.lastname: Chang
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Voloshina
authors.forename: Kathy
authors.initials: K
authors.lastname: Brown
authors.forename: William J
authors.initials: WJ
authors.lastname: Hucker
authors.forename: Igor R
authors.initials: IR
authors.lastname: Efimov
mesh_terms: D000200:Action Potentials; D000818:Animals; D016275:Atrial Function; D002304:Cardiac Pacing, Artificial; D018031:Connexin 43 / Q000032:analysis; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D005455:Fluorescent Antibody Technique; D006325:Heart Atria / Q000166:cytology; D006339:Heart Rate; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000502:physiology*; D055096:Optical Devices; D012815:Signal Processing, Computer-Assisted; D012849:Sinoatrial Node / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D013997:Time Factors
chemical_list: D018031:Connexin 43