Biomedical Engineering and Bioengineering Commons^™

Alagebrium Inhibits Neointimal Hyperplasia And Restores Distributions Of Wall Shear Stress By Reducing Downstream Vascular Resistance In Obese And Diabetic Rats, Hongfeng Wang, Dorothee Weihrauch, Judy R. Kersten, Jeffrey M. Toth, Anthony G. Passerini, Anita Rajamani, Sonja Schrepfer, John F. Ladisa Jr.

Biomedical Engineering Faculty Research and Publications

Mechanisms of restenosis in type 2 diabetes mellitus (T2DM) are incompletely elucidated, but advanced glycation end-products (AGEs)-induced vascular remodeling likely contributes. We tested the hypothesis that AGEs-related collagen cross-linking (ARCC) leads to increased downstream vascular resistance (DVR), and altered in-stent hemodynamics, thereby promoting neointimal hyperplasia (NH) in T2DM. We proposed that decreasing ARCC with ALT-711 (Alagebrium) would mitigate this response. Abdominal aortic stents were implanted in Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. Blood flow, vessel diameter, and wall shear stress (WSS) were calculated after 21 days, and NH was quantified. Arterial segments (aorta, carotid, iliac, femoral, arterioles) …

Altered Hemodynamics, Endothelial Function, And Protein Expression Occur With Aortic Coarctation And Persist After Repair, Arjun Menon, Thomas J. Eddinger, Hongfeng Wang, David C. Wendell, Jeffrey M. Toth, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Coarctation of the aorta (CoA) is associated with substantial morbidity despite treatment. Mechanically induced structural and functional vascular changes are implicated; however, their relationship with smooth muscle (SM) phenotypic expression is not fully understood. Using a clinically representative rabbit model of CoA and correction, we quantified mechanical alterations from a 20-mmHg blood pressure (BP) gradient in the thoracic aorta and related the expression of key SM contractile and focal adhesion proteins with remodeling, relaxation, and stiffness. Systolic and mean BP were elevated for CoA rabbits compared with controls leading to remodeling, stiffening, an altered force response, and endothelial dysfunction both …

Including Aortic Valve Morphology In Computational Fluid Dynamics Simulations: Initial Findings And Application To Aortic Coarctation, David C. Wendell, Margaret M. Samyn, Joseph Richard Cava, Laura M. Ellwein, Mary M. Krolikowski, Kimberly L. Gandy, Andrew N. Pelech, Shawn C. Shadden, John F. Ladisa

Biomedical Engineering Faculty Research and Publications

Computational fluid dynamics (CFD) simulations quantifying thoracic aortic flow patterns have not included disturbances from the aortic valve (AoV). 80% of patients with aortic coarctation (CoA) have a bicuspid aortic valve (BAV) which may cause adverse flow patterns contributing to morbidity. Our objectives were to develop a method to account for the AoV in CFD simulations, and quantify its impact on local hemodynamics. The method developed facilitates segmentation of the AoV, spatiotemporal interpolation of segments, and anatomic positioning of segments at the CFD model inlet. The AoV was included in CFD model examples of a normal (tricuspid AoV) and a …

Computational Simulations Demonstrate Altered Wall Shear Stress In Aortic Coarctation Patients Previously Treated By Resection With End-To-End Anastomosis, John F. Ladisa, Ronak Jashwant Dholakia, Alberto Figueroa, Irene E. Vignon-Clementel, Frandics P. Chan, Margaret M. Samyn, Joseph Richard Cava, Charles A. Taylor, Jeffrey A. Feinstein

Biomedical Engineering Faculty Research and Publications

Background.  Atherosclerotic plaque in the descending thoracic aorta (dAo) is related to altered wall shear stress (WSS) for normal patients. Resection with end-to-end anastomosis (RWEA) is the gold standard for coarctation of the aorta (CoA) repair, but may lead to altered WSS indices that contribute to morbidity.

Methods.  Computational fluid dynamics (CFD) models were created from imaging and blood pressure data for control subjects and age- and gender-matched CoA patients treated by RWEA (four males, two females, 15 ± 8 years). CFD analysis incorporated downstream vascular resistance and compliance to generate blood flow velocity, time-averaged WSS (TAWSS), and oscillatory shear …

Lung Circulation Modeling: Status And Prospect, Anne V. Clough, Said H. Audi, Robert C. Molthen, Gary S. Krenz

Biomedical Engineering Faculty Research and Publications

Mathematical modeling has been used to interpret anatomical and physiological data obtained from metabolic and hemodynamic studies aimed at investigating structure-function relationships in the vasculature of the lung, and how these relationships are affected by lung injury and disease. The indicator dilution method was used to study the activity of redox processes within the lung. A steady-state model of the data was constructed and used to show that pulmonary endothelial cells may play an important role in reducing redox active compounds and that those reduction rates can be altered with oxidative stress induced by exposure to high oxygen environments. In …

Changes In Pulmonary Arterial Wall Mechanical Properties And Lumenal Architecture With Induced Vascular Remodeling, Robert C. Molthen, Amy Heinrich, Steven Thomas Haworth, Christopher A. Dawson

Biomedical Engineering Faculty Research and Publications

To explore and quantify pulmonary arterial remodeling we used various methods including micro-CT, high-resolution 3-dimensional x-ray imaging, to examine the structure and function of intact pulmonary vessels in isolated rat lungs. The rat is commonly used as an animal model for studies of pulmonary hypertension (PH) and the accompanying vascular remodeling, where vascular remodeling has been defined primarily by changes in the vessel wall composition in response to hypertension inducing stimuli such as chronic hypoxic exposure (CHE) or monocrotaline (MCT) injection. Little information has been provided as to how such changes affect the vessel wall mechanical properties or the lumenal …