Abstract
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.
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 language | English |
|---|---|
| Journal | PLoS ONE |
| DOIs | |
| Publication status | Published - 5 Sept 2017 |
