Hemodynamic assessment of pulmonary hypertension in mice: a model based analysis of the disease mechanism

Umar Qureshi, M., Colebank, M. J., Paun, L. M., Ellwein, L., Chesler, N., Haider, M. A., Hill, N. A. , Husmeier, D. and Olufsen, M. S. (2019) Hemodynamic assessment of pulmonary hypertension in mice: a model based analysis of the disease mechanism. Biomechanics and Modeling in Mechanobiology, 18(1), pp. 219-243. (doi:10.1007/s10237-018-1078-8) (PMID:30284059)

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Abstract

This study uses a one-dimensional fluid dynamics arterial network model to infer changes in hemodynamic quantities associated with pulmonary hypertension in mice. Data for this study include blood flow and pressure measurements from the main pulmonary artery for 7 control mice with normal pulmonary function and 5 mice with hypoxia-induced pulmonary hypertension. Arterial dimensions for a 21-vessel network are extracted from micro-CT images of lungs from a representative control and hypertensive mouse. Each vessel is represented by its length and radius. Fluid dynamic computations are done assuming that the flow is Newtonian, viscous, laminar, and has no swirl. The system of equations is closed by a constitutive equation relating pressure and area, using a linear model derived from stress–strain deformation in the circumferential direction assuming that the arterial walls are thin, and also an empirical nonlinear model. For each dataset, an inflow waveform is extracted from the data, and nominal parameters specifying the outflow boundary conditions are computed from mean values and characteristic timescales extracted from the data. The model is calibrated for each mouse by estimating parameters that minimize the least squares error between measured and computed waveforms. Optimized parameters are compared across the control and the hypertensive groups to characterize vascular remodeling with disease. Results show that pulmonary hypertension is associated with stiffer and less compliant proximal and distal vasculature with augmented wave reflections, and that elastic nonlinearities are insignificant in the hypertensive animal.

Item Type:Articles
Additional Information:Funding This study was supported by the National Science Foundation (NSF) awards NSF-DMS # 1615820, NSF-DMS # 1246991 and Engineering and Physical Sciences Research Council (EPSRC) of the UK, grant reference number EP/N014642/1.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Paun, Miss Luiza Mihaela and Hill, Professor Nicholas and Husmeier, Professor Dirk
Authors: Umar Qureshi, M., Colebank, M. J., Paun, L. M., Ellwein, L., Chesler, N., Haider, M. A., Hill, N. A., Husmeier, D., and Olufsen, M. S.
College/School:College of Science and Engineering > School of Mathematics and Statistics > Mathematics
College of Science and Engineering > School of Mathematics and Statistics > Statistics
Journal Name:Biomechanics and Modeling in Mechanobiology
Publisher:Springer
ISSN:1617-7959
ISSN (Online):1617-7940
Published Online:03 October 2018

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
694461EPSRC Centre for Multiscale soft tissue mechanics with application to heart & cancerRaymond OgdenEngineering and Physical Sciences Research Council (EPSRC)EP/N014642/1M&S - MATHEMATICS