title: Increased cell membrane capacitance is the dominant mechanism of stretch-dependent conduction slowing in the rabbit heart: a computational study.
abstract: Volume loading of the cardiac ventricles is known to slow electrical conduction in the rabbit heart, but the mechanisms 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. First, a simplified geometric model with prescribed homogeneous deformation was used to fit model parameters and characterize individual MEF mechanisms, and showed good qualitative agreement with experimentally measured strain-CV relations. A 3D model of the rabbit left and right ventricles was then compared with experimental measurements from optical electrical mapping studies in the isolated rabbit heart. The model was inflated 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 effects 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.
authors.affiliation: Simula Research Laboratory, Lysaker, Norway.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: de Oliveira
authors.affiliation: Bioengineering Department, University of California, San Diego.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Pfeiffer
authors.affiliation: Simula Research Laboratory, Lysaker, Norway; Department of Informatics, University of Oslo, Norway.
authors.forename: Joakim
authors.initials: J
authors.lastname: Sundnes
authors.affiliation: Simula Research Laboratory, Lysaker, Norway.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Wall
authors.affiliation: Bioengineering Department, University of California, San Diego.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
keywords: Mechano-electric feedback; bidomain model; cell membrane; multiscale model; pressure loaded heart; stretch-activated currents; tissue conductivity