An in silico approach to monitor and predict haemodynamics during safety pharmacology studies

International audienceThe present work is related to develop in silico models in order to predict the impact of drugs on the haemodynamics. More precisely, we propose a simplified mathematical model able to take into account vasoconstriction and vasodilatation phenomena to reproduce the ROTSAC experiment (i.e., the Rodent Oscillatory Tension Set-Up to study Arterial Compliance). The calibration of the model allows to directly estimate the mechanical properties of the vessel (such as the Young modulus, active pre-stress, etc.). The objective of this work is to numerically reproduce the experimental data and to understand the mechanisms involved in the impact of the drug on the mechanical behaviour of the vessel. During the ROTSAC experiments, an aortic segment is mounted between two metal hooks in an organ bath. A current source is used to control the distension force and clamp frequency of a force–length transducer. The stretch protocol was applied with physiological frequency (10 Hz) and amplitude (40 mmHg). The measured quantities are force and displacement of the aortic segment (in length and width). We build a mathematical model aiming at describing the ROTSAC experiment. The inputs of the model are the force measured in the experiment and the parameters describing the behaviour of the material (Young modulus, Poisson ratio, active pre-stress and elastic modulus, initial length, width and thickness of the aortic segment). The output of the model is the displacement (in length and width) of the aortic segment. It is important to note that these parameters are unknown and must be determined through a process known as calibration. The purpose of the calibration is estimating some unknown inputs of the model such that the outputs match the experimental measurements. The calibration procedure makes it possible to estimate the unknown model parameters from the ROTSAC static and dynamic data. Thanks to the calibration we have access to physical quantities that cannot be directly measured from the ROTSAC experiment. This paves the way for understanding the underlying mechanisms of a drug on the vessel mechanics

A consensus protocol for functional connectivity analysis in the rat brain

International audienc