Submitted on August 25, 2006
Accepted on January 25, 2007
Mechano-electric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics
Nico Kuijpers1*, Huub ten Eikelder1, Peter Bovendeerd1, Sander Verheule2, Theo Arts3, and Peter Hilbers4
1 Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands
2 Physiology, Maastricht University, Maastricht, Netherlands
3 Biophysics, Maastricht University, Maastricht, Netherlands
4 Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, Netherlands
* To whom correspondence should be addressed. E-mail: N.H.L.Kuijpers{at}tue.nl.
Atrial fibrillation is a common cardiac arrhythmia and is promoted by atrial dilatation. Acute atrial dilatation may play a role in atrial arrhythmogenesis through mechano-electric feedback. In experimental studies conduction slowing and block has been observed in acutely dilated atria. In the present study, the influence of the stretch-activated current Isac on impulse propagation is investigated by means of computer simulations. Both homogeneous and inhomogeneous atrial tissue are modeled by cardiac fibers composed of segments that are electrically and mechanically coupled. Active force is related to the concentration of free calcium ions as well as to the sarcomere length. Simulations of homogeneous and inhomogeneous cardiac fibers have been performed to quantify the relation between the conduction velocity and Isac under stretch. In our model, conduction slowing and block is related to the amount of stretch and is enhanced by contraction of early activated segments. Conduction block can be unidirectional in an inhomogeneous fiber and is promoted by a shorter stimulation interval. Slowing of conduction is explained by inactivation of INa channels and a lower maximum upstroke velocity (dVmem/dt)max due to a depolarized resting membrane potential. Conduction block at shorter stimulation intervals is explained by a longer effective refractory period under stretch. Our observations are in agreement with experimental results and explain the large differences in intra-atrial conduction as well as the increased inducibility of atrial fibrillation observed in acutely dilated atria.
