| The pathological changes that give rise to ventricular arrhythmias likely occur at both the membrane level of the myocyte—through alterations in ion channels, pumps and carriers—and at the tissue level—in the ventricular geometry and myofiber organization. We have developed a method to simulate electrical propagation through the myocardium that incorporates highly detailed measurements of ventricular anatomy with detailed descriptions of membrane biophysics. We have verified that diffusion tensor magnetic resonance imaging (DTMRI) can provide accurate measurements of myofiber orientation by direct correlation with histology in perfused and fixed hearts. DTMRI was used to reconstruct the ventricular anatomy and myofiber organization at a resolution 1 to 2 times that previously attainable. Characteristics such as the apical fiber vortex and the longitudinal trend of fiber imbrication were visualized using this method. Fiber imbrication was found to be larger that generally assumed. It appears DTMRI might provide an assessment of the laminar architecture of the ventricles, as well. We have simulated electrical propagation in DTMRI derived models of the ventricles using a continuum approach. A methodology for simulating normal activation and recovery with a concordant QRST complex is presented. Finally, using an anatomically-based, biophysically detailed model, it is shown that changes in membrane proteins that lead to early afterdepolarizations in isolated myocytes can result in a reentrant arrhythmia at the level of the intact ventricles. |
