Section: Research Program

Excitable systems and heartbeat signal analysis

We are developing novel approaches to heartbeat signal analysis for understanding chronic atrial fibrillation. The noisy aspect of data recorded by electrodes, on the inner surface of human atria during episodes of atrial fibrillation, exhibit intriguing features for excitable media. Instead of phase chaos as typically expected, it shares many common traits of non-equilibrium fluctuations in disordered systems or strong turbulence. To assess those peculiar observations we investigate a synaptic plasticity that affects conduction properties. Electrical synapses comprise many different kinds of connexins, which may be affected by diverse factors, so we use a generic approach. Slight detuning of their linear response leads to an instability of the modulating agents, here an excess charge. Acting on slow time scales of repolarisation, it is understood as collective modes propagating through and retroacting on each synapse: the medium is desynchronised. It is not a syncytium. We propose to associate transient states with a phenomenon called electrical remodelling, which has not received any accepted description thus far. Moreover, from the properties of the model it is possible to start exploring phase space. Transitions between different regimes could help decipher stages in the evolution of the disease from acute to chronic, one main goal of cardiovascular research.

Theoretically, a myocardium is an excitable tissue acting under normal circumstances as a functional syncytium of myocardial cells. Models of excitability for the heart are reaction-diffusion systems describing the propagation of electric pulses called action potentials similarly to models for axons. Reaction results from ionic exchange cycles between the cytoplasm of excitable cells and their extra-cellular medium, when initiated by a stimulus above some threshold. Pulses are robust topological structures.

Considering the stable fixed point as a phase resetting state, chaos may arise in spatio-temporal sequences. This is the paradigm for cardiac fibrillation. But, it is incompatible with the following observations: the distributions of amplitudes all collapse on a scaling function G. We map exponents on data patients provided by IHU LIRYC showing non-universal properties. Singular exponents are observed with consistent Hausdorff dimension of sets D(h). Negative contribution is high, suggesting an underlying multiplicative process.

Excess charge in cells like of Ca may perturb the dynamics of synapses. We consider a physiologically plausible linear response of synapses to the electro-chemical potential. This response is unknown as of today. The new dynamics may interact with excitability. It has the specific form of a Rayleigh instability. Cycles become retarded or advanced. Hopf bifurcation and chaos are allowed creating EADs (Early After Depolarization). Regarding propagation, pulses are pinned and released on a chaotic background. Cycle modulations create defects via facilitation through the third dimension. Defects proliferate creating a glassy phase, which back-scatter fronts in 1D and roughens them in 2D. Further effective inhibitor diffusion splits them. Electrical remodelling is here the abnormal modification of the cell dynamics without any membrane alteration.

There are features of Self Organized Criticality (SOC) in large regions of phase space. Pulses have a phase and propagate on a random medium. For instance one paradigm we investigate would be:

t θ + sin ( θ + φ ˜ ) = Ω + x x θ (3)

(θ: phase of activation front, Ω: tachycardia frequency, φ˜: phase perturbation). Randomness reactualises non-linearly, which tells that the noise is quenched and reset. For instance in 1 + 1D, spatio-temporal maps look very much like optimal directed paths along diagonals. In 1 + 2D, we are guessing that pulses do propagate in the (q)KPZ universality class, just as the remodelling front does. This class is only fractal, but together with large deviations of the fluctuations, it may be consistent with a multi-affine process. Physiologically, one interesting bonus is the interpretation of non-reentrant Tachycardia as dislocation patterns slowly evolving.