Subthreshold parameters of cardiac tissue in a bi-layer computer model of heart failure.

Abstract

Current density threshold and liminal area are subthreshold parameters of the cardiac tissue that indicate its susceptibility to external and internal stimulations. Extensive experimental and theoretical research has been conducted to quantify these two parameters in normal conditions for both animal and human models. Here we employed a 2D numerical model of human cardiac tissue to assess these subthreshold parameters under the pathological conditions of heart failure and fibrosis. Stimuli were applied over an area ranging from 0.04 to 1 mm² using various pulse durations. The current density threshold decreased with increasing stimulation area or pulse duration. No significant changes were found in both parameters between control conditions and heart failure in the atrial tissue, while in the ventricular tissue, heart failure resulted in significantly reduced excitability with higher stimulation current magnitudes needed for excitation and larger liminal areas. This results from the specific ionic remodeling in ventricular heart failure that affects both subthreshold active currents such as I(K₁) and connexin 43 conductance. In fibrosis, increased fibroblast to myocyte coupling coefficient had a non-linear influence on current density thresholds, with an initial increase of current magnitude followed by a relaxation phase down to the current magnitude threshold for the control condition with no fibrosis. The results show that subthreshold excitation properties of the myocardium are influenced in a complex, non-linear manner by cardiac pathologies. Such observations may contribute to our understanding of impulse capturing properties, relevant, for example, for the generation of ectopic foci-originated arrhythmias and for the efficient design of cardiac stimulating electrodes.