Validation of three-dimensional conduction models using experimental mapping: are we getting closer?

The anisotropic material properties, irregular geometry, and specialized conduction system of the heart all affect the three-dimensional (3D) spread of electrical activation. A limited number of research groups have tried accounting for these features in 3D conduction models to investigate more thoroughly their observations of cardiac electrical activity in 3D experimental preparations. The full potential of these large scale conduction models, however, has not been realized because of a lack of quantitative validation with experiment. Such validation is critical in order to use the models to predict the electrical response of the myocardium to drugs or electrical stimulation. In this paper, a quantitative, experimental validation of paced activation in a 3D conduction model of a 3 cm x 3 cm x 1 cm section of the ventricular wall is presented. Epicardial and intramural pacing stimuli were applied in the center of a 528 channel electrode plaque sutured to the left ventricle in dogs. Unipolar electrograms were recorded at 2 kHz during and after pacing. Fiber directions within the tissue below the electrodes were estimated histologically and from pace-mapping. Simulated epicardial electrograms were computed for surface paced beats using our 3D bidomain model of the mapped tissue volume incorporating the measured fiber directions. Extracellular potentials and isochronal maps resulting from paced activations in both model and experiment were directly compared. Preliminary results demonstrate that our 3D model reproduces qualitatively such key features of the experimental data as electrogram morphologies and epicardial conduction velocities. Though quantitative agreement between model and experiment was only moderate, the validation approach described herein is an essential first step in assessing the predictive capability of present day conduction models.