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A COMBINED EXPERIMENTAL AND COMPUTATIONAL APPROACH TO STUDY THE BIOLOGIC EFFECT OF HEMODYNAMICS IN END-TO-SIDE VASCULAR BYPASS GRAFTS

Kute, Stephanie Michelle (2002) A COMBINED EXPERIMENTAL AND COMPUTATIONAL APPROACH TO STUDY THE BIOLOGIC EFFECT OF HEMODYNAMICS IN END-TO-SIDE VASCULAR BYPASS GRAFTS. Doctoral Dissertation, University of Pittsburgh.

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    Abstract

    A diseased artery often becomes blocked, compromising blood flow to downstream tissues and organs. One common surgical intervention is to bypass this blocked region with a vascular graft. However, these grafts can fail due to an overhealing response, known as intimal hyperplasia (IH), which occurs at the graft/artery junction (i.e., anastomosis). The goal of this research was to determine if a quantitative correlation exists between the hemodynamic phenomena at the distal anastomosis of a vascular bypass graft and carefully selected, acute biological precursors of intimal hyperplasia.To accomplish this task, we perfused porcine, artery-artery, end-to-side and end-to-end anastomoses ex vivo and developed computational fluid dynamics (CFD) models incorporating the reconstructed geometry and perfusion conditions present in each experimental anastomosis. The perfusion experiments allowed us to assess the levels of immediate early gene (IEG) proteins and vascular cell apoptosis at various regions along the anastomoses. Since the pressure and flow rate in the ex vivo perfusion model were precisely known, the CFD models utilized this information along with the 3D reconstructed anastomotic geometries to accurately estimate wall shear stress (WSS) and WSS gradient (WSSG) in the same regions of interest. This process allowed for a distinct and unique coupling between the perfusion experiments and the computational simulations that has not been achieved previously. Through linear and nonlinear regression analyses on this directly-coupled data, we found that low levels of WSS and WSSG cause upregulation of IEG proteins. Because increased levels of IEG expression leads to IH formation, our results suggest that low levels of WSS and WSSG correlate with increased IH formation. Our coupled experimental and computational approach has allowed us to evaluate IEG protein expression by vascular cells in response to the hemodynamics present in vascular anastomoses. Based on the correlations we found between low levels of WSS and WSSG and the subsequent increase in IEG protein expression, treatments such as graft geometry optimization or targeted gene therapy may improve the clinical success rate of vascular bypass grafts. However, some issues need to be addressed before the results of this study can be applied clinically.


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    Item Type: University of Pittsburgh ETD
    Creators/Authors:
    CreatorsEmailORCID
    Kute, Stephanie Michellesmkst50@pitt.edu
    Title: A COMBINED EXPERIMENTAL AND COMPUTATIONAL APPROACH TO STUDY THE BIOLOGIC EFFECT OF HEMODYNAMICS IN END-TO-SIDE VASCULAR BYPASS GRAFTS
    Status: Unpublished
    Abstract: A diseased artery often becomes blocked, compromising blood flow to downstream tissues and organs. One common surgical intervention is to bypass this blocked region with a vascular graft. However, these grafts can fail due to an overhealing response, known as intimal hyperplasia (IH), which occurs at the graft/artery junction (i.e., anastomosis). The goal of this research was to determine if a quantitative correlation exists between the hemodynamic phenomena at the distal anastomosis of a vascular bypass graft and carefully selected, acute biological precursors of intimal hyperplasia.To accomplish this task, we perfused porcine, artery-artery, end-to-side and end-to-end anastomoses ex vivo and developed computational fluid dynamics (CFD) models incorporating the reconstructed geometry and perfusion conditions present in each experimental anastomosis. The perfusion experiments allowed us to assess the levels of immediate early gene (IEG) proteins and vascular cell apoptosis at various regions along the anastomoses. Since the pressure and flow rate in the ex vivo perfusion model were precisely known, the CFD models utilized this information along with the 3D reconstructed anastomotic geometries to accurately estimate wall shear stress (WSS) and WSS gradient (WSSG) in the same regions of interest. This process allowed for a distinct and unique coupling between the perfusion experiments and the computational simulations that has not been achieved previously. Through linear and nonlinear regression analyses on this directly-coupled data, we found that low levels of WSS and WSSG cause upregulation of IEG proteins. Because increased levels of IEG expression leads to IH formation, our results suggest that low levels of WSS and WSSG correlate with increased IH formation. Our coupled experimental and computational approach has allowed us to evaluate IEG protein expression by vascular cells in response to the hemodynamics present in vascular anastomoses. Based on the correlations we found between low levels of WSS and WSSG and the subsequent increase in IEG protein expression, treatments such as graft geometry optimization or targeted gene therapy may improve the clinical success rate of vascular bypass grafts. However, some issues need to be addressed before the results of this study can be applied clinically.
    Date: 04 September 2002
    Date Type: Completion
    Defense Date: 17 July 2002
    Approval Date: 04 September 2002
    Submission Date: 05 July 2002
    Access Restriction: No restriction; The work is available for access worldwide immediately.
    Patent pending: No
    Institution: University of Pittsburgh
    Thesis Type: Doctoral Dissertation
    Refereed: Yes
    Degree: PhD - Doctor of Philosophy
    URN: etd-07052002-114228
    Uncontrolled Keywords: Apoptosis; C-fos; Computational Fluid Dynamics; Correlation; Egr-1; Endothelial Cell; Shear Stress; Smooth Muscle Cell; 3D Reconstruction; C-jun
    Schools and Programs: Swanson School of Engineering > Bioengineering
    Date Deposited: 10 Nov 2011 14:49
    Last Modified: 10 Nov 2011 15:18
    Other ID: http://etd.library.pitt.edu:80/ETD/available/etd-07052002-114228/, etd-07052002-114228

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