Short Term Memory and Discordant Alternans in the Heart

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In this project the PI will establish the role of short term memory in action potential duration (APD) restitution and the formation of spatially discordant alternans (SDA) in the heart using nonlinear spatio-temporal analysis of the heart's dynamics. The PI will use patch clamp and optical mapping techniques to perform recording from isolated cells and intact rabbit hearts. In the theoretical studies, the PI will use a phenomenological mathematical model, as well as 2D numerical simulations utilizing the recently developed detailed ionic rabbit ventricular cell model. The first objective of the proposed research is to demonstrate that the spatial distribution of short-term memory in the heart correlates with the onset of alternans and ventricular fibrillation (VF). The second objective of the proposal is to establish inter-ventricular differences in mechanisms of SDA formation in the heart. Using optical mapping of the isolated rabbit heart, the PI will test the hypothesis that the formation of SDA in the right and left ventricles of the heart occurs predominantly through different mechanisms: steep conduction velocity restitution and short term memory. The third objective of the research proposal is to assess the specific roles of short term memory and steep conduction velocity restitution in SDA formation. The PI will use a pharmacological approach to further tease out the individual contributions of these mechanisms to SDA formation in the heart. The project will train graduate and undergraduate students in a multidisciplinary environment. The project will have significant impact on our understanding of the fundamental causes and precursors of ventricular fibrillation, a major cause of death in humans.