ANR HR-CEM

The project “High Resolution Cardiac Electrophysiology Models: HR-CEM” within the ANR call Modèles Numériques started in November 2013 and lasted until November 2017.

This international project involved three partners: Inria (coordinator), IHU LIRYC, and UMI-CRM in Montréal (Canada). The project has external collaborators in Univ. Bordeaux and Univ. Pau.

Based on these collaborations and new developments in structural and functional imaging of the heart available at LIRYC, we plan to reconsider the concepts behind the models in order to improve the accuracy and efficiency of simulations. Cardiac simulation software and high-resolution numerical models will be derived from experimental data from animal models. Validation will be performed by comparing of simulation output with experimentally recorded functional data. The validated numerical models will be made available to the community of researchers who take advantage of in-silico cardiac simulation and, hopefully, become references. In particular we shall provide the first exhaustive model of an animal heart including the four chambers coupled through the special conduction network, with highly detailed microstructure of both the atria and the ventricles. Such a model embedded in high-performance computational software will provide stronger medical foundations for in-silico experimentation, and elucidate mechanisms of cardiac arrhythmias.

ANR MITOCARD

The MITOCARD project (Electrophysiology of Cardiac Mitochondria), coordinated by S. Arbault (Université de Bordeaux, ISM), was granted by the ANR in July 2017. The objective of MITOCARD is to improve understanding of cardiac physiology by integrating the mitochondrial properties of cell signaling in the comprehensive view of cardiac energetics and rhythm pathologies. It was recently demonstrated that in the heart, in striking contrast with skeletal muscle, a parallel activation by calcium of mitochondria and myofibrils occurs during contraction, which indicates that mitochondria actively participate in Ca2+ signaling in the cardiomyocyte. We hypothesize that the mitochondrial permeability transition pore (mPTP), by rhythmically depolarizing inner mitochondrial membrane, plays a crucial role in mitochondrial Ca2+ regulation and, as a result, of cardiomyocyte Ca2+ homeostasis. Moreover, mitochondrial reactive oxygen species (ROS) may play a key role in the regulation of the mPTP by sensing mitochondrial energetics balance. Consequently, a deeper understanding of mitochondrial electrophysiology is mandatory to decipher their exact role in the heart's excitation-contraction coupling processes. However, this is currently prevented by the absence of adequate methodological tools (lack of sensitivity or selectivity, time resolution, averaged responses of numerous biological entities). The MITOCARD project will solve that issue by developing analytical tools and biophysical approaches to monitor kinetically and quantitatively the Ca2+ handling by isolated mitochondria in the cardiomyocyte.

MITOCARD is a multi-disciplinary project involving 4 partners of different scientific fields: the CARMEN team as well as

GENCI