ABSTRACT
We use in silico experiments to study the role of the hemodynamics and of the type of disendothelization on the physiopathology of intimal hyperplasia. We apply a multiscale bio-chemo-mechanical model of intimal hyperplasia on an idealized axisymmetric artery that suffers two kinds of disendothelizations. The model predicts the spatio-temporal evolution of the lesions development, initially localized at the site of damages, and after few days displaced downstream of the damaged zones, these two stages being observed whatever the kind of damage. Considering macroscopic quantities, the model sensitivity to pathology-protective and pathology-promoting zones is qualitatively consistent with experimental findings. The simulated pathological evolutions demonstrate the central role of two parameters: (a) the initial damage shape on the morphology of the incipient stenosis, and (b) the local wall shear stresses on the overall spatio-temporal dynamics of the lesion.
Subject(s)
Arteries , Tunica Intima , Humans , Hyperplasia/pathology , Tunica Intima/pathology , Arteries/pathology , Hemodynamics , Stress, MechanicalABSTRACT
We consider a computational multiscale framework of a bio-chemo-mechanical model for intimal hyperplasia. With respect to existing models, we investigate the interactions between hemodynamics, cellular dynamics and biochemistry on the development of the pathology. Within the arterial wall, we propose a mathematical model consisting of kinetic differential equations for key vascular cell types, collagen and growth factors. The luminal hemodynamics is modeled with the Navier-Stokes equations. Coupling hypothesis among time and space scales are proposed to build a tractable modeling of such a complex multifactorial and multiscale pathology. A one-dimensional numerical test-case is presented for validation by comparing the results of the framework with experiments at short and long timescales. Our model permits to capture many cellular phenomena which have a central role in the physiopathology of intimal hyperplasia. Results are quantitatively and qualitatively consistent with experimental findings at both short and long timescales.
Subject(s)
Arteries , Hemodynamics , Arteries/pathology , Collagen , Humans , Hyperplasia/pathology , Models, TheoreticalABSTRACT
INTRODUCTION: The cardiopulmonary exercise test (CPET) and the 6-minute walk test (6MWT) are used to prescribe the appropriate training load for cycling and walking exercise in patients with chronic obstructive pulmonary disease (COPD). The primary aims were: (i) to compare estimated peak work rate (Wpeak(estimated)) derived from six existing Wpeak regression equations with actual peak work rate (Wpeak(actual)); and (ii) to derive a new Wpeak regression equation using six-minute walk distance (6MWD) and conventional outcome measures in COPD patients. METHODS: In 2906 patients with COPD, existing Wpeak regression equations were used to estimate Wpeak using 6MWD and a new equation was derived after a stepwise multiple regression analysis. RESULTS: The 6 existing Wpeak regression equations were inaccurate to predict Wpeak(actual) in 82% of the COPD patients. The new Wpeak regression equation differed less between Wpeak(estimated) and Wpeak(actual) compared to existing models. Still, in 74% of COPD patients Wpeak(estimated) and Wpeak(actual) differed more than (±) 5 watts. CONCLUSION: In conclusion, estimating peak work load from 6MWD in COPD is inaccurate. We recommend assessment of Wpeak using CPET during pre-rehabilitation assessment in addition to 6MWT.