Effect of cell geometry and gap junction conductance on wave propagation in myocardium: A computational approach

The conduction velocity and the path of propagation of electrical waves determine the effectiveness of contraction of the heart muscle. Areas of slow conduction and block may lead to the formation of cardiac arrhythmias, which may result in cardiac fibrillation and sudden cardiac death. Propagation of cardiac waves is determined by both passive and active properties of myocardium.;Cardiac disease, like heart failure and myocardial infarction, as well as aging result in changes in cell geometry and the remodeling of the ionic channels and intercellular gap junctions. The main objective of this thesis is to determine the effect of the cellular microstructure like cell geometry and intercellular gap junctions on propagation of the cardiac waves, using a sub-cellular computer model of myocardium.;We found that variations in cell size, with a constant cell length/width ratio, shows small effects on conduction velocities. The results were not dependent on gap junction distribution and conductance, or the details of the tissue architecture. Other parameters kept constant, length/width was a good predictor of the velocity of propagation and anisotropic ratio. These results indicate that cell shape is more important than cell size in determining conduction velocity of the propagating wave.;We also found that structural heterogeneities, due to spatial hetorogenetities in cell geometry or gap junction conductance lead to conduction block (a precursor of cardiac arrhythmias). Both, cell geometry and gap junctional conductance (among other factors) determine the tissue space constant. Conduction block occurred when a wave propagated into regions with a larger space constant (∼ 40--50% increase). As the ratio cell length/width increases the tissue space constant is less sensitive to changes in cell geometry and gap junction conductance. As a consequence, tissue architectures with more elongated cells (i.e. higher length/width ratio) are less sensitive to structural heterogeneities resulting from cell geometry and gap junction conductance. This findings may have important implications for tissue engineering, and the design of cardiac tissues.