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(Circulation Research. 2009;104:915.)
© 2009 American Heart Association, Inc.

Integrative Physiology

Structural and Functional Evidence for Discrete Exit Pathways That Connect the Canine Sinoatrial Node and Atria

Vadim V. Fedorov, Richard B. Schuessler, Matthew Hemphill, Christina M. Ambrosi, Roger Chang, Alexandra S. Voloshina, Kathy Brown, William J. Hucker, Igor R. Efimov

From the Department of Biomedical Engineering (V.V.F., M.H., C.M.A., R.C., A.S.V., K.B., W.J.H., I.R.E.), Washington University; and Division of Cardiothoracic Surgery (R.B.S.), Washington University School of Medicine, St Louis, Mo.

Correspondence to Vadim V. Fedorov, Department of Biomedical Engineering, Washington University, One Brookings Dr, St Louis, MO 63130. E-mail vadimfed{at}gmail.com or vfedorov@biomed.wustl.edu

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.

Key Words: sinoatrial node • optical mapping • sinoatrial exit block • connexin43