We have taken a multi-disciplinary approach that incorporates cell and organ physiology, genetics, molecular biology, signal processing and computer modeling to understand the complex interactions that promote fibrillation. Our laboratory has been studying several large animal models of atrial fibrillation and genetically altered mouse models of vulnerable (to atrial fibrillation) substrate. Two major areas of study in our laboratory are:

Mechanism of Fibrillation
Utilizing fluorescent techniques with voltage-sensitive dyes and Ca-sensitive dyes, with mapping systems that have a very high degree of spatial and temporal resolution, we are studying organ electrophysiology and cellular electrophysiology to determine the critical substrate to sustain rotors that drive atrial fibrillation. We are currently focusing on how alterations in gap junction expression, altered tissue structure (cell separation, fibrosis, invasion of imflammatory cells) create substrate for rotor development and stability. We also utilize higher-order signal processing to extract “order” of this seemingly disordered arrhythmia. We have found that there need not be alterations in cellular ion channels or single-cell electrophysiology to promote atrial fibrillation and that non-uniform anisotropy may be sufficient to the development of rotors and drivers. We have also identified key electrophysiologic features of the myocardium within the pulmonary vein that make this area fertile ground for these drivers.

Remodeling in Atrial Fibrillation
Several physiologic triggers (loosely called remodeling) are known to promote atrial fibrillation. Interestingly, atrial fibrillation itself induces changes that promote the sustenance of atrial fibrillation. In addition, atrial pressure overload and heart failure also promote changes (different ones though) that promote the substrate vulnerable to atrial fibrillation. However, it is not known what or how these changes occur. Our data suggest that migration of imflammatory cells and the development of fibrosis is key in this remodeling. We are studying several animal models of remodeling and transgenic models to identify the key factors in promoting these structural changes and are studying precisely how these changes affect electrophysiology. We have recently found that overexpression of TGF-ß promotes the vulnerable substrate for atrial fibrillation and may be a key factor in promoting structural changes during remodeling.