TY - JOUR
T1 - Local gradients in electrotonic loading modulate the local effective refractory period
T2 - implications for arrhythmogenesis in the infarct border zone
AU - Connolly, Adam
AU - Trew, Mark
AU - Smaill, Bruce
AU - Plank, Gernot
AU - Bishop, Martin
PY - 2015/4/9
Y1 - 2015/4/9
N2 - Ectopic electrical activity which originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture. Informed by 3D reconstructions of myocyte organization in the infarct border zone, a region of rapid tissue expansion is abstracted to an idealized representation. A novel metric is introduced that defines the local electrotonic loading as a function of passive tissue properties and boundary conditions. The effective refractory period correlates closely with local electrotonic loading, while the action potential duration, conduction and upstroke velocity reduce in regions of increasing electrotonic load. In the presence of focal ectopic stimuli, spatial variation in effective refractory period can cause uni-directional conduction block providing a substrate for reentrant arrhythmias. Consequently, based on the observed results a possible novel mechanism for arrhythmogenesis in the infarct border zone is proposed.
AB - Ectopic electrical activity which originates in the peri-infarct region can give rise to potentially lethal re-entrant arrhythmias. The spatial variation in electrotonic loading that results from structural remodelling in the infarct border zone may increase the probability that focal activity will trigger electrical capture, but this has not previously been investigated systematically. This study uses in-silico experiments to examine the structural modulation of effective refractory period on ectopic beat capture. Informed by 3D reconstructions of myocyte organization in the infarct border zone, a region of rapid tissue expansion is abstracted to an idealized representation. A novel metric is introduced that defines the local electrotonic loading as a function of passive tissue properties and boundary conditions. The effective refractory period correlates closely with local electrotonic loading, while the action potential duration, conduction and upstroke velocity reduce in regions of increasing electrotonic load. In the presence of focal ectopic stimuli, spatial variation in effective refractory period can cause uni-directional conduction block providing a substrate for reentrant arrhythmias. Consequently, based on the observed results a possible novel mechanism for arrhythmogenesis in the infarct border zone is proposed.
U2 - 10.1109/TBME.2015.2421296
DO - 10.1109/TBME.2015.2421296
M3 - Article
C2 - 25872206
SN - 1558-2531
JO - IEEE transactions on bio-medical engineering
JF - IEEE transactions on bio-medical engineering
IS - 99
ER -