Pathophysiology of cardiovascular diseases


Over the last decades, studies have shown that the mechanical stresses exerted by the blood flow have an important effect on the cells comprised in the arterial walls and on the circulating cells. Mechanical forces have the potential to stimulate changes in the cell shape, orientation, secretion, rate of apoptosis and even gene expression.

The goal is therefore to better understand the mechanisms responsible for the development of vascular diseases by studying the interaction between mechanical forces and biochemical processes that occur in the cells.

Effects of mechanical stimuli on the growth of Abdominal Aortic Aneurysms

An abdominal aortic aneurysms is a local abnormal dilatation that develops in the aorta, the largest artery that carries blood from the heart to the rest of the body (Figure 1). This vascular disease has become a major health issue that predominantly affects men over 60 years of age. In most cases, the growth of the aneurysm remains unnoticed, until rupture occurs, rupture being a life-threatening event with mortality rates as high as 80%.

In order to estimate the role that mechanical stimuli play in the growth mechanisms of the aneurismal dilatations, we aim at determining the spatial and temporal distributions of the forces induced by the blood flow and characterising their evolution as the aneurysm grows.

 

Figure 1: Sketch of an abdominal aortic aneurysm. It develops along the abdominal aorta, below the arterial bifurcation to the kidneys.

A parametric study has been conducted in axisymmetric and non-axisymmetric models of aneurysms, whose dimensions have been systematically increased. The flow field inside rigid models of aneurysms has been measured using Particle Image Velocimetry (PIV) under the same pulsatile flow conditions as the ones measured in the abdominal aorta in a healthy patient at rest (collaboration with the Department of Mechanical and Aerospace Engineering at University of California, San Diego – USA and with the LadHyX at the Ecole Polytechnique – France). The interactions between the pulsatile flow and the compliant walls have been simulated numerically using a finite-element code, LifeV (collaboration with INRIA at Rocquencourt – France).

The major event is the flow separation that occurs even at early stages (dilatation ≤ 50%) as the flow decelerates. In axisymmetric aneurysms, a large vortex ring forms and impacts the downstream aneurysm wall (Figure 2a). Two regions with distinct patterns of wall shear stresses (WSS) have been identified: an upstream region of flow detachment, with low oscillatory WSS, and a downstream region of flow reattachment, where large negative WSS are produced as a result of the impact of the vortex ring. For non-axisymmetric aneurysms, a hairpin vortex is shed, which stays attached to the wall with the smallest curvature. As the vortex detaches, it rotates and impinges on the latter wall. The wall with the largest curvature is, however, subjected to quasi-steady reversed WSS of very low magnitude.

Lagrangian tracking of blood cells inside the different models of aneurysms shows a dramatic increase in the cell residence time as the aneurysm grows. While recirculating, cells experience high shear stresses close to the walls and inside the shear layers, which may lead to cell activation (Figure 2b). The vortical structure of the flow also convects the cells towards the wall, increasing the probability for cell deposition and ipso facto for the formation of an intraluminal thrombus.  

Figure 2: (a) Spatial distribution of velocities measured by Particle Image Velocimetry (PIV) in a medium size aneurysm at 3 consecutive instants of time. The flow detaches from the wall around the peak systole (time when the heart expulses the peak flow rate). A vortex ring forms and impinges on the downstream wall, leading to low wall stresses upstream and high wall stresses downstream. (b) Effects of the vortex structures on the trajectories of cells, calculated by Lagrangian particle tracking.



Collaborators:

Prof. Juan Lasheras, University of California San Diego, La Jolla
Dr. Jean-Marc Chomaz, Ecole Polytechnique, Palaiseau
Dr.Steven Sparks
Dr. Miguel Fernández, INRIA Rocquencourt
Prof. Patrick Le Tallec, Ecole Polytechnique, Palaiseau
Dr. Marina Vidrascu, INRIA Rocquencourt