|Authors||B. L. de Oliveira, J. Sundnes, S. Wall and A. D. McCulloch|
|Title||Increased 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)|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Journal||Cellular and Molecular Bioengineering|
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.