Grantee: The Ohio State University, Columbus, OH, USA
Researcher: Thomas J. Hund, Ph.D.
Grant Title: Synchronization of spontaneous activity in the cardiac pacemaker
https://doi.org/10.37717/220020368
Program Area: Studying Complex Systems
Grant Type: Scholar Award
Amount: $450,000
Year Awarded: 2013
Duration: 6 years
Each heartbeat represents the emergent behavior of a complex network of coupled and highly heterogeneous excitable cells. In fact, the apparent simplicity of the normal heart rhythm belies the underlying complexity of a vast and highly nonlinear system. The true complex nature of this amazing biological network is most apparent in the setting of cardiovascular disease, where abnormal electrical rhythms or arrhythmias are responsible for the majority of almost 400,000 deaths each year.1 Despite tremendous progress over the past two decades in understanding the link between monogenic molecular defects and dysfunction at the level of the intact organ, we lack even a theoretical framework to understand the simple process of initiation and maintenance of regular heart rhythm. At the same time, in a more general sense, new approaches are needed to understand the laws governing selforganization and emergent behavior of complex systems. My research program seeks to understand the rules that govern selection of alternative stable states and synchronization in systems of delay-coupled oscillators, with a particular focus on the cardiac pacemaker.
While the heart has long been used as a laboratory to glean greater truths about the behavior of complex systems, progress in this area has largely stalled within the past ten years. Our research will apply a systems approach to a well-defined question that has to-date not benefitted from this approach and will develop new tools to facilitate the integration of mathematical modeling and experiment in an iterative manner that is essential for advancing the study of complex systems. The sinoatrial node, or cardiac pacemaker, serves as an ideal system to develop greater understanding of complex systems behavior. First, the cardiac pacemaker complex is a multi-scale, highly nonlinear and heterogenous system, presenting a compelling and non-trivial challenge in terms of behavior analysis. Second, the technology has only recently advanced to the point where it is possible to experimentally determine important system parameters/variables related to SAN activity at the level of the single channel, cell and intact tissue. Third, a reductionist approach to understanding cellular mechanisms for SAN automaticity delivers diminishing returns. New approaches are clearly needed to move the field forward. Finally (fourth), sinus node dysfunction is a major health problem in our rapidly aging population. Thus, new insights generated by this program may have important implications for increasingly burdened healthcare systems in the United States and abroad.