AuthorsB. L. de Oliveira, J. Sundnes, S. Wall and A. D. McCulloch
TitleIncreased Membrane Capacitance Is the Dominant Mechanism of Stretch-Dependent Conduction Slowing in the Rabbit Heart: a Computational Study
Afilliation, , Scientific Computing
Project(s)Center for Biomedical Computing (SFF)
StatusPublished
Publication TypeJournal Article
Year of Publication2015
JournalCellular and Molecular Bioengineering
Volume8
Issue2
Pagination237-246
Publisher
Abstract

Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mech- anisms remain unclear. Previous experimental and modeling studies have investigated some of these mechanisms, including stretch-activated membrane currents, reduced gap junctional conductance, and altered cell membrane capacitance. In order to quantify the relative contributions of these mechanisms, we combined a monomain model of rabbit ventricular electrophysiology with a hyperelastic model of passive ventricular mechanics. After a simplied geometric model with prescribed homogeneous deformation had been used to t model parameters and charcterize individual MEF mechanisms, a 3D model of the rabbit left and right ventricles was compared with experimental measurements from optical electrical mapping studies in the isolated rabbit heart. The model was in ated to an end-diastolic pressure of 30 mmHg, resulting in epicardial strains comparable to those measured in the anterior left ventricular free wall. While the e ects of stretch activated channels did alter epicardial conduction velocity, an increase in cellular capacitance was required to explain previously reported experimental results. The new results suggest that for large strains, various mechanisms can combine and produce a biphasic relationship between strain and conduction velocity. However, at the moderate strains generated by high end-diastolic pressure, a stretch- induced increase in myocyte membrane capacitance is the dominant driver of conduction slowing during ventricular volume loading.

Citation KeySimula.simula.2704