Computational assessment of the functional role of sinoatrial node exit pathways in the human heart.

Sanjay Kharche, Edward Vigmond, Igor Efimov, Halina Dobrzynski

Research output: Contribution to journalArticlepeer-review


Aim: The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical
mapping experiments suggest that the SAN is functionally insulated from atrial tissue
except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs.
Additionally, histological imaging suggests the presence of a secondary pacemaker
close to the SAN. We hypothesise that a) an insulating border-SEP anatomical
configuration is related to SAN arrhythmia; and b) a secondary pacemaker, the
paranodal area, is an alternate pacemaker but accentuates tachycardia. A 3D electroanatomical
computational model was used to test these hypotheses.
Methods: A detailed 3D human SAN electro-anatomical mathematical model was
developed based on our previous anatomical reconstruction. Electrical activity was
simulated using tissue specific variants of the Fenton-Karma action potential equations.
Simulation experiments were designed to deploy this complex electro-anatomical
system to assess the roles of border-SEPs and paranodal area by mimicking
experimentally observed SAN arrhythmia. Robust and accurate numerical algorithms
were implemented for solving the mono domain reaction-diffusion equation implicitly,
calculating 3D filament traces, and computing dominant frequency among other
quantitative measurements.
Results: A centre to periphery gradient of increasing diffusion was sufficient to permit
initiation of pacemaking at the centre of the 3D SAN. Re-entry within the SAN, micro
re-entry, was possible by imposing significant SAN fibrosis in the presence of the
insulating border. SEPs promoted the micro re-entry to generate more complex SANatrial
tachycardia. Simulation of macro re-entry, i.e. re-entry around the SAN, was
possible by inclusion of atrial fibrosis in the presence of the insulating border. The
border shielded the SAN from atrial tachycardia. However, SAN micro-structure
intercellular gap junctional coupling and the paranodal area contributed to prolonged
atrial fibrillation. Finally, the micro-structure was found to be sufficient to explain shifts
of leading pacemaker site location.
Conclusions: The simulations establish a relationship between anatomy and SAN
electrical function. Microstructure, in the form of intercellular gap junction coupling, was
found to regulate SAN function and arrhythmia.
Original languageEnglish
JournalPLoS ONE
Publication statusPublished - 5 Sept 2017


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