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Computational and Mathematical Methods in Medicine
Volume 2013 (2013), Article ID 618326, 12 pages
http://dx.doi.org/10.1155/2013/618326
Research Article

Influence of Distal Resistance and Proximal Stiffness on Hemodynamics and RV Afterload in Progression and Treatments of Pulmonary Hypertension: A Computational Study with Validation Using Animal Models

1Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, CO 80309, USA
2Department of Bioengineering, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA

Received 29 May 2013; Revised 9 September 2013; Accepted 25 September 2013

Academic Editor: Eduardo Soudah

Copyright © 2013 Zhenbi Su et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

We develop a simple computational model based on measurements from a hypoxic neonatal calf model of pulmonary hypertension (PH) to investigate the interplay between vascular and ventricular measures in the setting of progressive PH. Model parameters were obtained directly from in vivo and ex vivo measurements of neonatal calves. Seventeen sets of model-predicted impedance and mean pulmonary arterial pressure (mPAP) show good agreement with the animal measurements, thereby validating the model. Next, we considered a predictive model in which three parameters, PVR, elastic modulus (EM), and arterial thickness, were varied singly from one simulation to the next to study their individual roles in PH progression. Finally, we used the model to predict the individual impacts of clinical (vasodilatory) and theoretical (compliance increasing) PH treatments on improving pulmonary hemodynamics. Our model (1) displayed excellent patient-specific agreement with measured global pulmonary parameters; (2) quantified relationships between PVR and mean pressure and PVS and pulse pressure, as well as studiying the right ventricular (RV) afterload, which could be measured as a hydraulic load calculated from spectral analysis of pulmonary artery pressure and flow waves; (3) qualitatively confirmed the derangement of vascular wall shear stress in progressive PH; and (4) established that decreasing proximal vascular stiffness through a theoretical treatment of reversing proximal vascular remodeling could decrease RV afterload.