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.
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“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
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- Lewis T, 1920, Heart, 191
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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
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