Tachyarrhythmias seen clinically and in experimental animal preparations usually involve regions of slow conduction and preferentially oriented lines of block within the reentrant circuit. These arrhythmias arise in regions of the myocardium bordering an infarct with significant changes in tissue fiber structure caused by healing or remodeling. This work is testing the hypothesis that abrubt changes in the macroscopic fiber structure serve as critical points in the formation of lines of block within reentrant circuits by redistributing currents and increasing the dispersion of recovery. The goal is to develop a predictive mechanism for arrhythmogenesis in tissue regions near a healing or healed infarct. A combined experimental/modeling approach is being used. High resolution epicardial potential mapping and MRI diffusion tensor imaging (Center for In Vivo Microscopy) is used to characterize the three dimensional fiber structure in vivo and to investigate its effect on activation wavefronts in normal  ventricular myocardium and in myocardium with pathways defined by cryoablation lesions. State-of-the-art, realistic computer models of the myocardium that incorporate a full description of the complex fiber structure, intramural variation, tissue geometry, and ionic-based membrane kinetic descriptions are being used to test the hypothesis that non-uniformities in tissue structure affect the activation and recovery processes in different ways. The research will impact the ongoing development of new promising targeted therapies for  arrhythmia management, such as cell transplantation or ablation. Chris Penland, Kevin Sampson, Joe Tranquillo

Funding for this work comes in part from the National Institutes of Health and the American Heart Association.