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Experimental Investigation of Mechanical Blood Damage Relevant to the Operation of Circulatory-Assist Devices

Sivek, Amanda D (2015) Experimental Investigation of Mechanical Blood Damage Relevant to the Operation of Circulatory-Assist Devices. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Circulatory-assist devices (CAD) are commonly used in clinical practice for end stage cardiovascular disease patients as a bridge to transplant or as destination therapy. Despite decades of research, mechanical blood damage remains a problem in the clinical utilization of CAD, which results in a myriad of patient complications including device-induced erythrocyte lysis (hemolysis), bleeding and thrombosis. There is a clinical need to better understand the mechanisms of flow-induced blood damage to aid in the design and clinical utilization of CAD with enhanced biocompatibility as well as to determine specific factors responsible for blood damage and methods of their assessment.
The objectives were to study in vitro the mechanisms of flow-induced blood trauma and the parameters that affect in vitro hemolysis testing of CAD. The tested hypotheses were: 1) Mechanically induced polymer degradation in a high molecular weight polyethylene oxide (PEO) solution could predict the degree of shear-induced hemolysis within a CAD candidate without the use of animal or human blood; 2) Blood bank storage of packed red blood cells (RBC) could adversely affect RBC mechanical properties which may reduce the efficiency of RBC transfusion in CAD patients; 3) Cell-cell interactions and suspension viscosity are potential mechanisms of flow-induced hemolysis; and 4) The geometry of micro-gaps and crevices in CAD blood flow paths could affect cell trafficking at supra-physiological shear stresses relevant to operating CAD.
We demonstrated that polymer mechanical degradation was highly correlated with hemolysis obtained due to circulation in the same CAD circuit as blood and ascertained valuable information on CAD performance predicting blood trauma without the need to use blood. We found that RBC deformability significantly decreased during blood bank storage which contributes to blood damage produced by CAD. Moreover, two additional mechanisms of flow-induced hemolysis relevant to operating CAD, cell-cell collisions and suspension viscosity, were elucidated. Finally, recirculating regions were observed in 100 µm wide rectangular and triangular crevices but not in wider crevices studied up to 500 µm, thus demonstrating the importance of the width of gaps and crevices in CAD blood flow paths for potential thrombogenesis.
This work provided information on mechanisms of flow-induced hemolysis and elucidated an important variable affecting thrombosis development in CAD blood flow paths at flow conditions relevant to in vitro and in vivo CAD operation. These results can contribute to the computational analysis, design and preclinical testing of next generation CAD.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Sivek, Amanda Ddalya@upmc.edu0000-0002-3179-8516
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairKameneva, Marina Vkamenevamv@upmc.eduMARINA
Committee CoChairAntaki, James Fantaki@cmu.edu
Committee MemberBorovetz, Harvey Sborovetzhs@upmc.eduBOROVETZ
Committee MemberKoepsel, Richard Rrkoepsel@andrew.cmu.edu
Date: 9 June 2015
Date Type: Publication
Defense Date: 27 March 2015
Approval Date: 9 June 2015
Submission Date: 28 March 2015
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 241
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Hemolysis, Thrombosis, Mechanical blood damage, In vitro, Normalized Index of Hemolysis, Circulatory-assist device, Ventricular-assist device, Microfluidics, Shear stress, RBC deformability, RBC mechanical fragility
Date Deposited: 09 Jun 2015 13:46
Last Modified: 19 Dec 2016 14:42
URI: http://d-scholarship.pitt.edu/id/eprint/24195

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