Arnaud Collet

A multi-scale cardiovascular system model can account for the load-dependence of the end-systolic pressure-volume relationship

BackgroundThe end-systolic pressure-volume relationship is often considered as a load-independent property of the heart and, for this reason, is widely used as an index of ventricular contractility. However, many criticisms have been expressed against this index and the underlying time-varying elastance theory: first, it does not consider the phenomena underlying contraction and second, the end-systolic pressure volume relationship has been experimentally shown to be load-dependent.MethodsIn place of the time-varying elastance theory, a microscopic model of sarcomere contraction is used to infer the pressure generated by the contraction of the left ventricle, considered as a spherical assembling of sarcomere units. The left ventricle model is inserted into a closed-loop model of the cardiovascular system. Finally, parameters of the modified cardiovascular system model are identified to reproduce the hemodynamics of a normal dog.ResultsExperiments that have proven the limitations of the time-varying elastance theory are reproduced with our model: (1) preload reductions, (2) afterload increases, (3) the same experiments with increased ventricular contractility, (4) isovolumic contractions and (5) flow-clamps. All experiments simulated with the model generate different end-systolic pressure-volume relationships, showing that this relationship is actually load-dependent. Furthermore, we show that the results of our simulations are in good agreement with experiments.ConclusionsWe implemented a multi-scale model of the cardiovascular system, in which ventricular contraction is described by a detailed sarcomere model. Using this model, we successfully reproduced a number of experiments that have shown the failing points of the time-varying elastance theory. In particular, the developed multi-scale model of the cardiovascular system can capture the load-dependence of the end-systolic pressure-volume relationship.

Temperature, geometry, and bifurcations in the numerical modeling of the cardiac mechano-electric feedback

This article characterizes the cardiac autonomous electrical activity induced by the mechanical deformations in the cardiac tissue through the mechano-electric feedback. A simplified and qualitative model is used to describe the system and we also account for temperature effects. The analysis emphasizes a very rich dynamics for the system, with periodic solutions, alternans, chaotic behaviors, etc. The possibility of self-sustained oscillations is analyzed in detail, particularly in terms of the values of important parameters such as the dimension of the system and the importance of the stretch-activated currents. It is also shown that high temperatures notably increase the parameter ranges for which self-sustained oscillations are observed and that several attractors can appear, depending on the location of the initial excitation of the system. Finally, the instability mechanisms by which the periodic solutions are destabilized have been studied by a Floquet analysis, which has revealed period-doubling phenomena and transient intermittencies.

Autonomous Electrical Activity Induced by Cardiac Tissue Deformation in a Thermo-Electro-Mechanical Background

Abstract In a healthy heart, the mechano-electric feedback (MEF) process acts as an intrinsic regulatory mechanism of the myocardium which allows the normal cardiac contraction by damping mechanical perturbations in order to generate a new healthy electromechanical situation. However, under certain conditions, the MEF can be a generator of dramatic arrhythmias by inducing local electrical depolarizations as a result of abnormal cardiac tissue deformations, via stretch-activated channels (SACs). Then, these perturbations can propagate in the whole heart and lead to global cardiac dysfunctions. In the present study, we examine the spatio-temporal behavior of the autonomous electrical activity induced by the MEF when the heart is subject to temperature variations. For instance, such a situation can occur during a therapeutic hypothermia. This technique is usually used to prevent neuronal injuries after a cardiac resuscitation. From this perspective, we introduce a one-dimensional time-dependent model containing all the key ingredients that allow accounting for excitation-contraction coupling, MEF and thermoelectric coupling. Our simulations show that an autonomous electrical activity can be induced by cardiac deformations, but only inside a certain temperature interval. In addition, in some cases, the autonomous electrical activity takes place in a periodic way like a pacemaker. We also highlight that some properties of the action potentials that are generated by the MEF, are significantly influenced by temperature. Moreover, in the situation where a pacemaker activity occurs, we also show that the period is heavily temperature-dependent.

Modèle unidimensionnel instationnaire de l’activité pacemaker cardiaque induite par le feedback mécano-électrique dans un environnement thermo-électromécanique

AIM OF THE STUDY In a healthy heart, the mechanoelectric feedback (MEF) process acts as an intrinsic regulatory mechanism of the myocardium which allows the normal cardiac contraction by damping mechanical perturbations in order to generate a new healthy electromechanical situation. However, under certain conditions, the MEF can be a generator of dramatic arrhythmias by inducing local electrical depolarizations as a result of abnormal cardiac tissue deformations, via stretch-activated channels (SACs). Then, these perturbations can propagate in the whole heart and lead to global cardiac dysfunctions. In the present study, we qualitatively investigate the influence of temperature on autonomous electrical activity generated by the MEF. METHOD We introduce a one-dimensional time-dependent model containing all the key ingredients that allow accounting for the excitation-contraction coupling, the MEF and the thermoelectric coupling. RESULTS Our simulations show that an autonomous electrical activity can be induced by cardiac deformations, but only inside a certain temperature interval. In addition, in some cases, the autonomous electrical activity takes place in a periodic way like a pacemaker. We also highlight that some properties of action potentials, generated by the mechanoelectric feedback, are significantly influenced by temperature. Moreover, in the situation where a pacemaker activity occurs, we also show that the period is heavily temperature-dependent. CONCLUSIONS Our qualitative model shows that the temperature is a significant factor with regards to the electromechanical behavior of the heart and more specifically, with regards to the autonomous electrical activity induced by the cardiac tissue deformations.