Heart Rhythm Insights Into Structural Remodeling in Atrial Tissue: Timed Automata Approach

The heart rhythm of a person following heart transplantation (HTX) is assumed to display an intrinsic cardiac rhythm because it is significantly less influenced by the autonomic nervous system—the main source of heart rate variability in healthy people. Therefore, such a rhythm provides evidence for arrhythmogenic processes developing, usually silently, in the cardiac tissue. A model is proposed to simulate alterations in the cardiac tissue and to observe the effects of these changes on the resulting heart rhythm. The hybrid automata framework used makes it possible to represent reliably and simulate efficiently both the electrophysiology of a cardiac cell and the tissue organization. The curve fitting method used in the design of the hybrid automaton cycle follows the well-recognized physiological phases of the atrial myocyte membrane excitation. Moreover, knowledge of the complex architecture of the right atrium, the ability of the almost free design of intercellular connections makes the automata approach the only one possible. Two particular aspects are investigated: impairment of the impulse transmission between cells and structural changes in intercellular connections. The first aspect models the observed fatigue of cells due to specific cardiac tissue diseases. The second aspect simulates the increase in collagen deposition with aging. Finally, heart rhythms arising from the model are validated with the sinus heart rhythms recorded in HTX patients. The modulation in the impairment of the impulse transmission between cells reveals qualitatively the abnormally high heart rate variability observed in patients living long after HTX

Ergodicity versus non-ergodicity for Probabilistic Cellular Automata on rooted trees

In this article we study a class of shift-invariant and positive rate probabilistic cellular automata (PCA) on rooted d-regular trees $\mathbb{T}^d$. In a first result we extend the results of [10] on trees, namely we prove that to every stationary measure $\nu$ of the PCA we can associate a space-time Gibbs measure $\mu_{\nu}$ on $\mathbb{Z} \times \mathbb{T}^d$. Under certain assumptions on the dynamics the converse is also true. A second result concerns proving sufficient conditions for ergodicity and non-ergodicity of our PCA on d-ary trees for $d\in \{ 1,2,3\}$ and characterizing the invariant product Bernoulli measures.Comment: 17 page

Cardiac cell modelling: Observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field

Computational Modeling, Formal Analysis, and Tools for Systems Biology.

As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science

Stimulateur cardiaque biologique : effets de la répartition spatiale des cardiomyocytes avec activité spontanée et de l'étirement uniaxial

La bradycardie est une maladie caractérisée par un rythme cardiaque trop lent. L'implantation définitive d'un stimulateur cardiaque électronique (SCE) est souvent envisagée dans le cadre du traitement. Cet appareil réduit la morbidité et la mortalité chez certains patients, mais présente de nombreux inconvénients, notamment la durée limitée de la batterie, l'inflammation et le remodelage tissulaire. Le stimulateur cardiaque biologique (SCB) est possiblement une alternative thérapeutique au SCE. Il est développé in vivo à partir de la manipulation de canaux ioniques, d'injection de cellules souches ou de reprogrammation somatique. La plupart de ces méthodes ne tiennent compte ni de la répartition spatiale aléatoire des cardiomyocytes avec activité spontanée, ni du couplage mécano-électrique. L'objectif de la thèse est d'investiguer en quoi ces deux phénomènes pourraient influencer l'activité spontanée du SCB. La première étude, théorique, démontre que la répartition spatiale aléatoire des cardiomyocytes avec activité spontanée, a priori inconnue, pourrait induire une variabilité intrinsèque non négligeable de l'activité spontanée du SCB. La variabilité intrinsèque, définie comme la différence de performance observée expérimentalement entre des SCB développés dans les mêmes conditions, peut affecter négativement le taux de succès des implantations chez le patient. La deuxième étude, également théorique, démontre que la force de l'automaticité (i.e. la capacité du cardiomyocyte autonome à dépolariser ses voisins non autonomes) et l'anisotropie structurelle linéaire pourraient moduler la variabilité intrinsèque du SCB, sans toutefois l'éliminer. La dernière étude, expérimentale, caractérise les effets de l’étirement uniaxial chez les SCB en monocouche de culture, et met en lumière le double rôle de stabilisateur temporel et spatial de ce type de stimulus mécanique. Collectivement, ces études démontrent que la répartition spatiale des cardiomyocytes avec activité spontanée et le couplage mécano-électrique sont des phénomènes important dont il faudrait tenir compte avant l’implantation du SCB au patient.Bradycardia refers to pathologically slow heart rhythm. Implantation of an electronic pacemaker (EP) is a standard treatment. Despite reducing morbidity and mortality in appropriate patients, EPs display many shortcomings, notably limited lifespan of the battery, inflammation and tissue remodeling. Biological pacemakers (BPs) may be a therapeutic alternative to EPs. They are created in vivo via ionic channels manipulation, stem cells injection or somatic reprogramming. Those methods usually ignore the random spatial disposition of spontaneous cardiomyocytes and mechano-electric coupling. This thesis aims to investigate the effects of those two phenomena on the spontaneous activity of the BP. Our first project, a theoretical study, demonstrated that random spatial disposition of spontaneous cardiomyocytes, a priori unknown, may induce non negligible intrinsic variability in the BP's spontaneous activity. Intrinsic variability, defined as performance disparities experimentally observed among BPs created under the same protocol, may compromise success rate of implantations to the patient. Our second project, another theoretical study, demonstrated that automaticity strength (the autonomous cardiomyocyte’s ability to drive its quiescent neighbors) and linear structural anisotropy may modulate but not eliminate intrinsic variability. Our last project, an experimental study, characterized effects of uniaxial stretch in BP monolayer cultures, and revealed both temporal and spatial stabilizing roles of that type of mechanical stimulus. Together, those studies stress that random spatial disposition of spontaneous cardiomyocytes and cardiac mechano-electric coupling are important phenomena that most be taken into account before BP's implantation to the patient

Synchronization of spatiotemporal patterns and modeling disease spreading using excitable media

Studies of the photosensitive Belousov-Zhabotinsky (BZ) reaction are reviewed and the essential features of excitable media are described. The synchronization of two distributed Belousov-Zhabotinsky systems is experimentally and theoretically investigated. Symmetric local coupling of the systems is made possible with the use of a video camera-projector scheme. The spatial disorder of the coupled systems, with random initial configurations of spirals, gradually decreases until a final state is attained, which corresponds to a synchronized state with a single spiral in each system. The experimental observations are compared with numerical simulations of two identical Oregonator models with symmetric local coupling, and a systematic study reveals generalized synchronization of spiral waves. Modeling studies on disease spreading have been reviewed. The excitable medium of the photosensitive BZ reaction is used to model disease spreading, with static networks, dynamic networks, and a domain model. The spatiotemporal dynamics of disease spreading in these complex networks with diffusive and non-diffusive connections is characterized. The experimental and numerical studies reveal that disease spreading in these model systems is highly dependent on the non-diffusive connections

Neutral coding - A report based on an NRP work session

Neural coding by impulses and trains on single and multiple channels, and representation of information in nonimpulse carrier