Characterization and Control of Wave Propagation in the Heart

Abstract

The heart is an excitable medium which supports the propagation of waves of electrical excitation. While these excitation waves enable the normal functioning of the heart, they also allow for self-sustained arrhythmic activity. Such self-sustained spiral wave activity underlies life-threatening cardiac arrhythmias such as ventricular fibrillation, and has to be treated with high-energy electrical shocks. However, electrical defibrillation may have severe side effects, including tissue damage and intolerable pain. Therefore, improving cardiac defibrillation is an important aim and requires a sound understanding of the mechanisms underlying the dynamics of fibrillation. This thesis focuses on the experimental characterization of the spatio-temporal dynamics and its control during ventricular fibrillation in Langendorff-perfused rabbit hearts. One aspect of the heart tissue is that its dynamical properties may change over time or be spatially heterogeneous. For example, ischemia due to reduced flow of blood affects spatial-temporal dynamics on the organ level as well as spatially localized variations of the tissue properties. In the first part of this thesis, the emphasis is on the characterization of the dynamics of ventricular fibrillation and in particular the dynamics of phase singularities at the core of the spiral waves. To achieve this goal for the optical mapping data, a novel approach for phase singularity identification and tracking is introduced. This method is applied to a pharmacological model of ischemia in the rabbit heart using Pinacidil. It is used to study the effect on spatial-temporal activation dynamics of ventricular fibrillation. Furthermore, the temporal fluctuations of the number of phase singularities observed on the heart surface is then investigated using a stochastic Markov model approach. We show that the Markov model captures essential properties and dynamics of phase singularities during ventricular fibrillation. The second part of the thesis studies the effect of spatial heterogeneity on fibrillatory dynamics. Using numerical simulations we investigate the interaction of phase singularities with heterogeneities and provide experimental observations of similar dynamical phenomena in the heart. The third part then analyzes how electrical shocks exert control on the ventricular fibrillation. The effect of a shock depends on its timing, and here a statistical approach is used to visualize and quantify its control. In summary, this thesis introduces and applies new methods to allow a more detailed characterization of the dynamics during ventricular fibrillation and its interaction with electrical shocks.