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Preclinical Biocompatibility Assessment of Cardiovascular Devices

Snyder, Trevor Arnoult (2006) Preclinical Biocompatibility Assessment of Cardiovascular Devices. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Bleeding and thromboembolism remain major complications of ventricular assist device (VAD) support. The amount of biocompatibility information that may be collected during preclinical studies is limited due to a lack of available assays, leaving the evaluation of investigational devices incomplete. To address these issues, flow cytometric assays were developed to quantify bovine circulating activated platelets, platelet microaggregates, platelet-leukocyte aggregates, and monocytes expressing tissue factor. Platelet lifespan was determined using an ex vivo biotinylation technique.These assays were applied in 50 animals receiving the Nimbus/Heartmate II axial flow VAD, 29 receiving the SunMedical EVAHEART centrifugal VAD, over 20 animals receiving a variety of other cardiovascular devices, and eight animals that underwent a sham VAD implantation procedure. The results demonstrated significantly increased circulating activated platelets and leukocytes, and cell aggregates following VAD implantation, which then usually declined to a lower but still significantly elevated level. Deviations from this pattern were observed in several pumps with obstructive thrombi in the blood flow path. Platelet life span decreased and platelet consumption correspondingly increased. The sham studies demonstrated that the effects of the implant procedure abated within three weeks. Thus, the ongoing platelet and leukocyte activation and aggregation, and decreased platelet life span could be attributed to the VADs, even while accounting for surgical effects.To identify the potential causes of the observed cellular activation, VAD surface modifications, revolutions per min increases, and anticoagulant regimen changes were evaluated in vivo. Two blood-shearing devices were constructed to investigate the effects of the supraphysiologic shear field within rotary VADs, although heat generation and sealing issues limited their effectiveness. Flow visualization of the Heartmate II VAD revealed vortices developed at low flow rates, frequently encountered in vivo.In conclusion, the propensity of cardiovascular devices to activate platelets and leukocytes was quantified, while accounting for the effects of the implant procedure. Through in vivo and in vitro investigations, it was demonstrated that the blood-contacting surface and adverse flow effects each contributed to the observed cellular activation. Thus, applying novel biocompatibility assays to preclinical studies, including those evaluating design enhancements and refinements, may be used to develop safer cardiovascular devices.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Snyder, Trevor Arnoulttasst61@pitt.eduTASST61
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWagner, William Rwagnerwr@upmc.eduWAGNER
Committee MemberBontempo, Franklin Afbontempo@itxm.orgFAB9
Committee MemberBorovetz, Harvey Sborovetzhs@upmc.eduBOROVETZ
Committee MemberAntaki, James
Committee MemberKormos, Robert Lkormosrl@upmc.eduKORMOS
Committee MemberFederspiel, William Jfederspielwj@upmc.eduWFEDERSP
Date: 2 June 2006
Date Type: Completion
Defense Date: 31 March 2006
Approval Date: 2 June 2006
Submission Date: 6 April 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
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: coatings; mechanical circulatory support; thrombosis; biomaterials; flow cytometry
Other ID:, etd-04062006-102142
Date Deposited: 10 Nov 2011 19:34
Last Modified: 19 Dec 2016 14:35


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