Mechanoelectric feedback leads to conduction slowing and block in acutely dilated atria: a modeling study of cardiac electromechanics.
Atrial fibrillation, a common cardiac arrhythmia, is promoted by atrial dilatation. Acute atrial dilatation may play a role in atrial arrhythmogenesis through mechanoelectric feedback. In experimental studies, conduction slowing and block have been observed in acutely dilated atria. In the present study, the influence of the stretch-activated current (I(sac)) on impulse propagation is investigated by means of computer simulations. Homogeneous and inhomogeneous atrial tissues are modeled by cardiac fibers composed of segments that are electrically and mechanically coupled. Active force is related to free Ca(2+) concentration and sarcomere length. Simulations of homogeneous and inhomogeneous cardiac fibers have been performed to quantify the relation between conduction velocity and I(sac) under stretch. In our model, conduction slowing and block are related to the amount of stretch and are 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 Na(+) channels and a lower maximum upstroke velocity 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 in acutely dilated atria.
Kuijpers
Nico H L
NH
Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands. N.H.L.Kuijpers@tue.nl
ten Eikelder
Huub M M
HM
Bovendeerd
Peter H M
PH
Verheule
Sander
S
Arts
Theo
T
Hilbers
Peter A J
PA
D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D016275:Atrial Function; D002118:Calcium / Q000378:metabolism; D003198:Computer Simulation; D004108:Dilatation, Pathologic / Q000150:complications; D025461:Feedback, Physiological; D006325:Heart Atria / Q000503:physiopathology; D006327:Heart Block / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D006329:Heart Conduction System / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007537:Isometric Contraction; D007551:Isotonic Contraction; D007700:Kinetics; D040542:Mechanotransduction, Cellular; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D015203:Reproducibility of Results; D012518:Sarcomeres / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
D015222:Sodium Channels; D012964:Sodium; D002118:Calcium