Vulnerability to atrial fibrillation under stretch can be explained by stretch-activated channels

N.H.L. Kuijpers, R.J. Rijken, H.M.M. Eikelder, ten, P.A.J. Hilbers

Research output: Chapter in Book/Report/Conference proceedingConference contributionAcademicpeer-review

4 Citations (Scopus)

Abstract

Experimental studies show an increased vulnerability to atrial fibrillation (AF) in acutely dilated atria. By application of a stretch-activated channel (SAC) blocker, vulnerability to AF decreases significantly, indicating a role for SACs in the initiation of AF. Using a computer model of cardiac electromechanics, we investigate the hypothesis that increased vulnerability to AF may be attributed to SACs. In our model, the human atria are represented by a triangular mesh obtained from MRI data. Electrophysiology is modeled by thirteen ionic membrane currents, including the stretch-activated current I_SAC and intracellular calcium handling. Mechanical behavior is modeled by a series elastic, a contractile, and a parallel elastic element. The contractile force is related to the intracellular concentration of free calcium as well as to the sarcomere length. To mimic acute dilatation, overall stretch is applied to the atria. Due to contraction of some areas, stretch increases in other areas, leading to a variation in I_SAC conductance. In the presence of I_SAC, the membrane potential depolarizes, which causes inactivation of the sodium channels and results in conduction slowing or block. Inducibility of AF increases under stretch, which is explained by an increased dispersion in atrial effective refractory period (AERP), conduction slowing and local conduction block. Our observations explain the large differences in intra-atrial conduction measured in experiments and provide insight in the vulnerability to AF in dilated atria.
Original languageEnglish
Title of host publicationProceedings of the 34th Annual Conference on Computers in Cardiology, 30 September - 3 October 2007, Durham NC, USA
Place of PublicationUnited States, Durham NC
Publication statusPublished - 2007

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