The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Conduction barriers and pathways of the sinoatrial pacemaker complex: their role in normal rhythm and atrial arrhythmias
Abstract
Since Keith and Flack's anatomical discovery of the sinoatrial node (SAN), the primary pacemaker of the heart, the question of how such a small SAN structure can pace the entire heart has remained for a large part unanswered. Recent advances in optical mapping technology have made it possible to unambiguously resolve the origin of excitation and conduction within the animal and human SAN. The combination of high-resolution optical mapping and histological structural analysis reveals that the canine and human SANs are functionally insulated from the surrounding atrial myocardium, except for several critical conduction pathways. Indeed, the SAN as a leading pacemaker requires anatomical (fibrosis, fat, and blood vessels) and/or functional barriers (paucity of connexins) to protect it from the hyperpolarizing influence of the surrounding atrium. The presence of conduction barriers and pathways may help explain how a small cluster of pacemaker cells in the SAN pacemaker complex manages to depolarize different, widely distributed areas of the right atria as evidenced functionally by exit points and breakthroughs. The autonomic nervous system and humoral factors can further regulate conduction through these pathways, affecting pacemaker automaticity and ultimately heart rate. Moreover, the conduction barriers and multiple pathways can form substrates for reentrant activity and thus lead to atrial flutter and fibrillation. This review aims to provide new insight into the function of the SAN pacemaker complex and the interaction between the atrial pacemakers and the surrounding atrial myocardium not only in animal models but also human hearts.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“there is a high degree of resemblance between human and canine sino-atrial (SA) node activity and structure (Review: (Fedorov, Glukhov, & Chang, 2012)), purkinje fiber distribution, and activation sequence (Allison, et al., 2007; Hamlin, 2007).”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Fedorov, et al., 2012
Citations
Cites
Total Excitation of the Isolated Human Heart
DURRER, D., van Dam, R. T., FREUD, G. E., Janse, M. J., MEIJLER, F. L., & ARZBAECHER, R. C. (1970) · Circulation · doi:10.1161/01.cir.41.6.899 · Cited by 1,779
The sinoatrial node, a heterogeneous pacemaker structure
Boyett, M. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00135-8 · Cited by 698
Keith, A., & Flack, M. (1907) · Europe PMC (PubMed Central) · Cited by 616
Molecular Architecture of the Human Sinus Node
Chandler, N. J., Greener, I. D., Tellez, J. O., Inada, S., Musa, H., Molenaar, P., DiFrancesco, D., Baruscotti, M., Longhi, R., Anderson, R. H., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.804369 · Cited by 400
Chauvin, M., Shah, D. C., Haı̈ssaguerre, M., Marcellin, L., & Brechenmacher, C. (2000) · Circulation · doi:10.1161/01.cir.101.6.647 · Cited by 396
Pacing-Induced Chronic Atrial Fibrillation Impairs Sinus Node Function in Dogs
Elvan, A., Wylie, K., & Zipes, D. P. (1996) · Circulation · doi:10.1161/01.cir.94.11.2953 · Cited by 325
Demonstration of a widely distributed atrial pacemaker complex in the human heart.
Boineau, J. P., Canavan, T. E., Schuessler, R. B., Cain, M. E., Corr, P. B., & Cox, J. L. (1988) · Circulation · doi:10.1161/01.cir.77.6.1221 · Cited by 305
Roles of adrenergic and cholinergic stimulation in spontaneous atrial fibrillation in dogs.
Sharifov, O., Fedorov, V., Beloshapko, G., Glukhov, A., Yushmanova, A., & Rosenshtraukh, L. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.09.030 · Cited by 305
Self-citationParadoxical Improvement of Impulse Conduction in Cardiac Tissue by Partial Cellular Uncoupling
Rohr, S., Kučera, J., Fast, V. G., & Kléber, A. G. (1997) · Science · doi:10.1126/science.275.5301.841 · Cited by 291
Mechanisms of sinoatrial pacemaker synchronization: a new hypothesis.
MICHAELS, D. C., Matyas, E. P., & Jalife, J. (1987) · Circulation Research · doi:10.1161/01.res.61.5.704 · Cited by 289
Anatomy of the human sinus node
James, T. N. (1961) · The Anatomical Record · doi:10.1002/ar.1091410205 · Cited by 259
Propagation through electrically coupled cells. How a small SA node drives a large atrium
Joyner, R. W., & van Capelle, F. J. (1986) · Biophysical Journal · doi:10.1016/s0006-3495(86)83559-7 · Cited by 253
THE INTER-AURICULAR TIME INTERVAL
Bachmann, G. (1916) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1916.41.3.309 · Cited by 233
Antz, M., Otomo, K., Arruda, M. S., Scherlag, B. J., Pitha, J. V., Tondo, C., Lazzara, R., & Jackman, W. M. (1998) · Circulation · doi:10.1161/01.cir.98.17.1790 · Cited by 227
Comparative Ultrastructure of the Sinus Node in Man and Dog
James, T. N., Sherf, L., Fine, G., & Morales, A. R. (1966) · Circulation · doi:10.1161/01.cir.34.1.139 · Cited by 224
Electrophysiological features of the mouse sinoatrial node in relation to connexin distribution
Verheijck, E. E. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00364-9 · Cited by 172
Zicha, S., Fernández‐Velasco, M., Lonardo, G., L’Heureux, N., & Nattel, S. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.02.011 · Cited by 171
Visualizing Excitation Waves inside Cardiac Muscle Using Transillumination
Baxter, W. T., Mironov, S. F., Зайцев, А. В., Jalife, J., & Pertsov, A. M. (2001) · Biophysical Journal · doi:10.1016/s0006-3495(01)76034-1 · Cited by 169
Zhang, H., Lau, D. H., Shlapakova, I. N., Zhao, X., Danilo, P., Robinson, R. B., Cohen, I. S., Qu, D. C., Xu, Z., & Rosen, M. R. (2011) · Cell Transplantation · doi:10.3727/096368911x565038 · Cited by 161
Optical Mapping of the Isolated Coronary-Perfused Human Sinus Node
Fedorov, V. V., Glukhov, A. V., Chang, R., Kostecki, G., Aferol, H., Hucker, W. J., Wuskell, J. P., Loew, L. M., Schuessler, R. B., Moazami, N., et al. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.098 · Cited by 159
Self-citationOrganisation of the mouse sinoatrial node: structure and expression of HCN channels
Liu, J., Dobrzynski, H., Yanni, J., Boyett, M. R., & Lei, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.11.016 · Cited by 156
Funny Current Downregulation and Sinus Node Dysfunction Associated With Atrial Tachyarrhythmia
Yeh, Y., Burstein, B., Qi, X. Y., Sakabe, M., Chartier, D., Comtois, P., Wang, Z., Kuo, C.-T., & Nattel, S. (2009) · Circulation · doi:10.1161/circulationaha.108.789677 · Cited by 137
The extent of the specialized atrioventricular ring tissues
Yanni, J., Boyett, M. R., Anderson, R. H., & Dobrzynski, H. (2009) · Heart Rhythm · doi:10.1016/j.hrthm.2009.01.021 · Cited by 133
Fedorov, V. V., Schuessler, R. B., Hemphill, M. A., Ambrosi, C. M., Chang, R., Voloshina, A. S., Brown, K. S., Hucker, W. J., & Efimov, I. R. (2009) · Circulation Research · doi:10.1161/circresaha.108.193193 · Cited by 127
Self-citationOpthof, T. (1988) · Cardiovascular Drugs and Therapy · doi:10.1007/bf02125744 · Cited by 124
Differential Expression of Gap Junction Proteins in the Canine Sinus Node
Kwong, K. F., Schuessler, R. B., Green, K. G., Laing, J. G., Beyer, E. C., Boineau, J. P., & Saffitz, J. E. (1998) · Circulation Research · doi:10.1161/01.res.82.5.604 · Cited by 121
COMPARATIVE MORPHOLOGY OF THE CARDIAC CONDUCTION TISSUE IN ANIMALS*
Truex, R. C., & Smythe, M. Q. (1965) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1965.tb49390.x · Cited by 118
EXPERIMENTS ON THE ORIGIN AND PROPAGATION OF THE IMPULSE IN THE HEART
Meek, W. J., & Eyster, J. A. E. (1914) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1914.34.4.368 · Cited by 112
Altered Right Atrial Excitation and Propagation in Connexin40 Knockout Mice
Bagwe, S., Berenfeld, O., Vaidya, D. M., Morley, G. E., & Jalife, J. (2005) · Circulation · doi:10.1161/circulationaha.104.527325 · Cited by 100
James, T. N. (2003) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2003.1 · Cited by 95
Widespread distribution and rate differentiation of the atrial pacemaker complex
Boineau, J. P., Schuessler, R. B., Hackel, D. B., Miller, C. B., Brockus, C. W., & Wylds, A. C. (1980) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1980.239.3.h406 · Cited by 92
James, T. N. (2002) · Progress in Cardiovascular Diseases · doi:10.1053/pcad.2002.130388 · Cited by 85
Glukhov, A. V., Fedorov, V. V., Anderson, M. E., Mohler, P. J., & Efimov, I. R. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00756.2009 · Cited by 83
Self-citationHistopathological correlates of sinoatrial disease.
Demoulin, J. C., & KULBERTUS, H. E. (1978) · Heart · doi:10.1136/hrt.40.12.1384 · Cited by 81
The influence of the atrial myocardium on impulse formation in the rabbit sinus node
Kirchhof, C. J. H. J., BONKE, F. I. M., Allessie, M. A., & Lammers, W. J. E. P. (1987) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00581916 · Cited by 75
Atrial Activation Mapping in Sinus Rhythm in the Clinical Electrophysiology Laboratory:
Cosío, F. G., Martin-Penato, A., Pastor, A., Núñez, A., MONTERO, M. A., Cantale, C. P., & SCHAMES, S. (2004) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.2004.03403.x · Cited by 75
Interatrial Electrical Connections: The Precise Location and Preferential Conduction
Sakamoto, S., Nitta, T., Ishii, Y., Miyagi, Y., Ohmori, H., & Shimizu, K. (2005) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2005.40659.x · Cited by 74
Fedorov, V. V., Hucker, W. J., Dobrzynski, H., Rosenshtraukh, L. V., & Efimov, I. R. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00022.2006 · Cited by 74
Self-citationReconstruction of the human sinoatrial node
Truex, R. C., Smythe, M. Q., & Taylor, M. J. (1967) · The Anatomical Record · doi:10.1002/ar.1091590406 · Cited by 72
Fedorov, V. V., Chang, R., Glukhov, A. V., Kostecki, G., Janks, D., Schuessler, R. B., & Efimov, I. R. (2010) · Circulation · doi:10.1161/circulationaha.109.935288 · Cited by 71
Self-citationFedorov, V. V., Ambrosi, C. M., Kostecki, G., Hucker, W. J., Glukhov, A. V., Wuskell, J. P., Loew, L. M., Moazami, N., & Efimov, I. R. (2011) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.111.962258 · Cited by 56
Self-citationBeau, S. L., Hand, D., Schuessler, R. B., Bromberg, B. I., Kwon, B., Boineau, J. P., & Saffitz, J. E. (1995) · Circulation Research · doi:10.1161/01.res.77.5.957 · Cited by 56
Connexin40 Imparts Conduction Heterogeneity to Atrial Tissue
Leaf, D. E., Feig, J. E., Vásquez, C., Riva, P. L., Yu, C., Lader, J. M., Kontogeorgis, A., Baron, E. L., Peters, N. S., Fisher, E. A. A., et al. (2008) · Circulation Research · doi:10.1161/circresaha.107.168997 · Cited by 56
Effect of canine cardiac nerves on heart rate, rhythm, and pacemaker location
Schuessler, R. B., Boineau, J. P., Wylds, A. C., Hill, D., Miller, C., & Roeske, W. R. (1986) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1986.250.4.h630 · Cited by 54
Mapping Cardiac Pacemaker Circuits
Efimov, I. R., Fedorov, V. V., Joung, B., & Lin, S. (2010) · Circulation Research · doi:10.1161/circresaha.109.209841 · Cited by 52
Self-citationBirchfield, R. I., Menefee, E. E., & BRYANT, G. D. N. (1957) · Circulation · doi:10.1161/01.cir.16.1.20 · Cited by 51
Delmar, M., Jalife, J., & MICHAELS, D. C. (1986) · The Journal of Physiology · doi:10.1113/jphysiol.1986.sp015926 · Cited by 47
Bromberg, B. I., Hand, D., Schuessler, R. B., & Boineau, J. P. (1995) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1995.269.3.h877 · Cited by 44
Sinus node automaticity during atrial fibrillation in isolated rabbit hearts.
Kirchhof, C. J. H. J., & Allessie, M. A. (1992) · Circulation · doi:10.1161/01.cir.86.1.263 · Cited by 39
Role of the Sinus Node in the Mechanism of Cholinergic Atrial Fibrillation
Nadeau, R. A., ROBERGE, F. A., & Billette, J. (1970) · Circulation Research · doi:10.1161/01.res.27.1.129 · Cited by 33
Abnormal Sinus Node Function in Clinical Arrhythmias
Schuessler, R. B. (2003) · Journal of Cardiovascular Electrophysiology · doi:10.1046/j.1540-8167.2003.02229.x · Cited by 30
Sinus Node Region as an Ultimate Source Driving Chronic Atrial Fibrillation
Takahashi, Y., Sanders, P., Rotter, M., Rostock, T., & Haı̈ssaguerre, M. (2005) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2005.50145.x · Cited by 8
Glukhov, A. V., Vargas-Pinto, P. A., Billman, G. E., Carnes, C. A., & Fedorov, V. V. (2011) · Circulation · doi:10.1161/circ.124.suppl_21.a9272 · Cited by 1
Self-citation
Research works printed but not linked: 5
- Glukhov AV, 2011, Circulation, 124, A9272, 10.1161/circ.124.suppl_21.A9272 · DOI
- Keith A, 1907, J Anat Physiol, 41, 172
- Lewis T, 1920, Heart, 191
- Lewis T, 1910, Heart, 147
- Wybauw R, 1910, Archives Internationales de Physiologie, 10, 78
Cited by
Sorted by citations
Small and large animal models in cardiac contraction research: advantages and disadvantages
Milani-Nejad, N., & Janssen, P. M. L. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.007 · Cited by 484
Dobrzynski, H., Anderson, R. H., Atkinson, A. J., Borbas, Z., D’Souza, A., Fraser, J. F., Inada, S., Logantha, S. J. R. J., Monfredi, O., Morris, G. M., et al. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.04.010 · Cited by 198
Transcriptomic Profiling of the Developing Cardiac Conduction System at Single-Cell Resolution
Goodyer, W. R., Beyersdorf, B. M., Paik, D. T., Tian, L., Li, G., Buikema, J. W., Chirikian, O., Choi, S. S., Venkatraman, S., Adams, E. L., et al. (2019) · Circulation Research · doi:10.1161/circresaha.118.314578 · Cited by 183
Glukhov, A. V., Kalyanasundaram, A., Lou, Q., Hage, L. T., Hansen, B. J., Belevych, A. E., Mohler, P. J., Knollmann, B. C., Periasamy, M., Györke, S., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht452 · Cited by 126
Self-citationFibrosis: a structural modulator of sinoatrial node physiology and dysfunction
Csepe, T. A., Kalyanasundaram, A., Hansen, B. J., Zhao, J., & Fedorov, V. V. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00037 · Cited by 123
Self-citation
Metadata
- Authors
- Fedorov, V. V., Glukhov, A. V., & Chang, R.
- Affiliations
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Fedorov, Vadim V.
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2012-05-01
- Volume
- 302
- Issue
- 9
- Pages
- H1773-H1783
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W1991705453
- Cited by
- 106
- References
- 54
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 9 · 2012: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart Research Institute
- Dorothy M. Davis Heart and Lung Research Institute
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- sinoatrial node, conductive pathways, atrial arrhythmias, atrial flutter, atrial fibrillation, reentry, optical mapping, connexins, atrial fibrosis, heart rate regulation, atrial pacemaker
- MeSH terms
- Animals, Arrhythmias, Cardiac, Autonomic Nervous System, Dogs, Heart Conduction System, Heart Rate, Humans, Sinoatrial Node, Atrial Function, Models, Animal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
