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

Abstract

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.

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

“…10) is often considered as the best tool for assessing cardiac contractility because the slope of this curve, named the end-systolic elastance (E es ), is assumed to be load-independent. However, the ESPVR has been shown to be load-dependent and non linear [5,7,8,9]. We also showed the non linearity of the ESPVR in Fig.…”

“…We also used the last version from the mechanical model of Negroni and Lascano [18]. A similar multiscale model was also built by Pironet et al [5] with the first model of Negroni and Lascano [16] but not with a complete cellular description: a calcium driver was used as an input for the mechanical model.…”

“…The fluid mechanics equations that govern such a system are described elsewhere [2,5,6] and only the cardiac pump model will be described in detail in the next section. …”

“…We choose a more physiological approach and described cardiac contraction at the cellular scale instead [4,5,13]. This heart model is described in the following sections.…”

“…Such macroscopic models are not based on the cardiac tissue Email address: sarah.kosta@ulg.ac.be (S. Kosta,) properties and cannot reproduce behaviors that arise from the microscopic scale. In this work, a cardiac cell contraction model is used and integrated at the organ level in order to get a multiscale model of the human CVS [4,5].…”